Search Results (285)

Background/Objectives: Diagnosing anterior cruciate ligament (ACL) insufficiency, particularly partial tears, remains challenging with standard static imaging. This study introduces a novel conceptual approach: assessing the dynamic kinematics of the infrapatellar fat pad (IPFP) as an indirect marker of ACL deficiency. Methods: In this biomechanical proof-of-concept study, dynamic ultrasound tracked IPFP kinematics in eight cadaveric knees evaluated in intact (Control), Sham, and Torn ACL states during passive flexion. The primary endpoints were (i) the absolute anteroposterior position at 90° (y₂ − y₁) and (ii) the posterior displacement during the 60–90° flexion arc (ΔY 60–90°). Results: ACL deficiency significantly altered deep-flexion IPFP kinematics. For ΔY 60–90°, the Torn ACL group demonstrated a substantial loss of posterior excursion compared to the Control group (Mean ± SD: −0.25 ± 1.03 vs. 2.88 ± 1.29 mm; Welch’s p < 0.001; Hedges’ g = 2.54, 95% CI: 1.18 to 3.89) and the Sham group (3.46 ± 1.63 mm; p < 0.001; g = −2.57, 95% CI: −3.90 to −1.25). Consequently, for y₂ − y₁ at 90°, the Torn ACL group remained abnormally anterior versus Control (p = 0.003; g = −1.97) and Sham (p < 0.001; g = −1.82). Conclusions: ACL deficiency induces a distinct reduction in posterior IPFP displacement. While these massive effect sizes establish a strong biomechanical rationale, this study serves as a foundational proof-of-concept. Large-scale in vivo clinical trials are strictly required to validate its diagnostic utility before clinical implementation. Full article

Radicular cysts (RCs) represent the most frequent inflammatory cystic lesions of the jaw, typically arising from non-vital teeth. While standard management via enucleation is well-documented, complex cases involving the anterior maxilla present significant surgical challenges due to their proximity to the nasal cavity floor (NCF) and the maxillary sinus floor (MSF). This report provides a comprehensive revision of a clinical case series involving seven patients (ages 17–50) treated with multimodal surgical and regenerative protocols. The patients were stratified into five distinct anatomical risk groups (A–E) based on the integrity of the bony boundaries and the presence of oronasal communications. The treatment strategies combined meticulous cyst enucleation with advanced regenerative techniques, including platelet-rich fibrin (PRF), allogeneic and xenograft bone substitutes, and local flaps such as the buccal fat pad (BFP). The results across all seven cases demonstrated favorable clinical and radiographic outcomes, with no instances of oronasal fistula formation or recurrence during follow-up periods ranging from 12 months to three years. This report emphasizes the necessity of structured anatomical stratification and multimodal planning to ensure scientific precision and surgical predictability in the management of complex maxillary lesions. The differences between approaches towards the nasal cavity and maxillary sinus have to be highlighted. Further studies with larger cohorts are warranted to evaluate the long-term outcomes of different treatment modalities. Full article

Osteoarthritis (OA) is a prevalent degenerative joint disease which affects millions of patients across the globe. The infrapatellar fat pad (IPFP) harbors diverse cell types with intricate intercellular interactions. Its mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) possess significant biological functions and hold promising applications in regenerative medicine. IPFP exhibits active secretory capacity, releasing adipokines including leptin and adiponectin, along with various cytokines. Furthermore, it contains a rich neural network playing a crucial role in knee pain perception and sensation. Moreover, IPFP and synovium can be considered an integrated unit, exhibiting interactions both with each other and with cartilage. In imaging applications, IPFP is gaining widespread attention as an emerging biomarker. In clinical practice, the decision to resect or preserve IPFP remains a controversial topic. This article will review the latest research regarding the mechanism of IPFP in OA, and discuss its clinical applications, providing a theoretical basis for the prevention and treatment of OA. Full article

Mesenchymal stem cells (MSCs) exert biological effects in part through their secretome which includes extracellular vesicles. In this study, we isolated and characterized the secretome from clinically relevant stem cell lines: human embryonic stem cell–derived mesenchymal stem cell line (ES-MSCs) and Infrapatellar fat pad derived MSC (IPFP-MSC) cultured in xeno-free medium. We assessed the biological activity of concentrated cell secretome or isolated fractions of extracellular vesicles (EVs) on cell proliferation, microvascular formation, and cartilage degradation in a human osteoarthritic (OA) ex vivo model. Serum-free conditioned medium from ES-MSC (N = 1) or IPFP-MSC (N = 2) monolayer cultures were concentrated by ultrafiltration to generate concentrated conditioned medium (CCM). Size exclusion chromatography was used to fractionate extracellular vesicles (EVs). Vesicle size, concentration, morphology, and surface markers were characterized by nanoparticle tracking analysis, transmission electron microscopy, and flow cytometry. Biological activity was evaluated by treating human umbilical vein endothelial cells (HUVECs), IPFP-MSCs, and ES-MSCs with CCM and EVs at defined particle concentrations. Endothelial network formation was tested in fibrin gels with different cell and secretome combinations. For analysis of cartilage degradation, human cartilage explants (N = 4; 3.5 mm in diameter) were harvested from patients undergoing total knee arthroplasty and subjected to IL-1β stimulation to induce an OA phenotype. Explants were treated with varying doses from CCM or EVs. Release of glycosaminoglycan in the medium and RNA analysis of catabolic genes were used as readouts. Secretome preparations yielded on average approximately 50 billion vesicles per mL with a similar particle size distribution between 50–200 nm in ES-MSC and IPFP-MSC cultures. Transmission electron microscopy confirmed vesicle morphology and flow cytometry confirmed expression of exosomal surface markers (CD9, CD63, CD81). Functionally, CCM and EVs enhanced proliferation in a dose-dependent manner. Endothelial networks formed by HUVECs in fibrin were stabilized over 7 days by CCMs, most notably by hypoxic ES-MSC CCM relative to no CCM treatment (control). In the OA cartilage model, IL-1β stimulation increased glycosaminoglycan release, whereas ES-MSC CCM treatment and EV treatment reduced glycosaminoglycan release and ES-MSC CCM reduced gene expression of IL-1β, MMP-1, and MMP-3. We isolated and characterized the concentrated secretome and the isolated vesicle-enriched fractions from xeno-free ES-MSC and IPFP-MSC and demonstrated bioactivity in promoting cell proliferation, modulating endothelial network formation, and mitigating cartilage degradation in osteoarthritic tissue. These findings support the bioactivity and therapeutic potential of stem cell–derived secretomes for OA. Full article

Background/Objectives: In recent decades, free flaps have emerged as the gold standard for head and neck reconstruction. However, their use is contraindicated in some cases due to advanced age and/or comorbidities. In such patients, a pedicled flap may be considered. The aim of this observational study was to evaluate strategies for head and neck reconstruction using pedicled flaps in the era of free flaps. Furthermore, the complication rate was analyzed. Methods: Patients who underwent head and neck reconstruction with pedicled flaps were included. The following flaps were considered: the pectoralis major (PMF), deltopectoral, platysma, frontal, temporal, nasolabial, supraclavicular artery island (SCAIF), infrahyoid, sternocleidomastoid, buccal fat pad, and facial artery myomucosal flap (FAMM). Patients’ characteristics, flap type, recipient sites, and flap-related complications were systematically recorded. Results: A total of 112 pedicled flaps were analyzed. A PMF was most commonly used for tongue and hypopharyngeal reconstruction. Partial and complete flap necrosis occurred in 11.6% and 1.8% of cases, respectively. Wound dehiscence was reported in 12.5% of cases, while pharyngo-/oro-cutaneous fistulas developed in 6.3% of patients. Hemorrhage from the donor site or flap occurred in 3.6% of cases, and pharyngeal stenosis in 0.9%. Conclusions: Each reconstructive strategy depends on the site and extent of tissue loss. Given the low complication rates, pedicled flaps remain a valid option for head and neck reconstruction in selected patients. Full article

Breast cancer progression and treatment responsiveness are significantly influenced by the tumor microenvironment. Therefore, transplantation into the mammary fat pad is widely employed to establish a mouse xenograft model of breast cancer. This study reports chimeric organoids derived from breast cancer xenografts composed of human and mouse cells. During passaging of an organoid line derived from breast cancer xenografts, characteristic cell clusters composed of smaller cells were observed. Immunostaining with a mouse-specific antibody revealed that the smaller cells were mouse cells composed of luminal- and basal-like cells. Chimeric organoids were observed in four of the six xenograft-derived organoid lines. Organoids composed solely of human cells rapidly diminished after passaging, with chimeric and mouse-cell-only organoids becoming predominant. When human breast cancer cells were co-cultured with mouse mammary epithelial cells, chimeras were frequently observed. The PCNA positivity rate in breast cancer cells within chimeras was higher than that in breast cancer cells within organoids composed solely of human cells. These findings indicate that xenograft-derived breast cancer organoids frequently contain mouse cells and that mouse mammary epithelial cells promote the proliferation of human breast cancer cells. Full article

The pathogenesis of primary osteoarthritis (OA) is complex and multifactorial. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor that regulates hundreds of genes involved with cytoprotection. The role of Nrf2 in OA remains undefined. We utilized the Hartley guinea pig model of primary OA to investigate the role of a purported Nrf2 activator, PB125, in delaying the onset of knee OA. We hypothesized that three months of daily PB125 supplementation would modify structural, molecular, and in vivo functional outcomes characteristic of disease. Fifty-six 2-month-old animals (equal sexes) were treated orally with PB125 or vehicle control for 3 months; animals were sacrificed at 5 months, which represents mild OA and early disease. Outcome measures included knee histopathology, mRNA expression, immunohistochemistry, and in vivo mobility. Notably, PB125 treatment had differing effects in males and females. Female PB125-treated animals had significantly decreased distal femur OA scores, accompanied by differential gene and protein expression patterns in articular cartilage for markers related to redox homeostasis; decreases in one compulsory mobility metric were also seen. In contrast, males demonstrated a statistical difference in voluntary mobility patterns. In summary, PB125 may modify the molecular mechanisms involved in the initiation of early OA in a potential sex-dependent fashion. Full article

Soft tissue sarcoma remains challenging to treat due to its heterogeneity, stemness-associated survival programs, and resistance to conventional therapies. Extracellular vesicles (EVs) mediate tumor–stroma communication, yet how stemness-targeted therapies reshape EVs-associated miRNAs networks remains unclear. This study profiled EVs miRNAs cargo from infrapatellar fat pad mesenchymal stem/stromal cells (IFP-MSCs) and sarcoma cells (SCs) under basal conditions and following treatment with a synthetic tyrosine peptide analog (TPA). EVs were isolated, characterized, and subjected to miRNAs profiling and pathway enrichment analyses. TPA induced ≥2-fold regulation of 182 miRNAs, including 49 upregulated and 24 downregulated in IFP-MSC-EVs and 86 upregulated and 23 downregulated in SC-EVs. A conserved core of 149 miRNAs (67.1%) was shared across all EVs groups. Abundant species included miR-3960 and miR-21-5p, while TPA reduced tumor-associated miRNAs such as miR-1246 (~10-fold decrease in IFP-MSC-EVs). Pathway enrichment revealed consistent targeting of cancer, MAPK, Wnt, TGF-β, and immune signaling pathways, with modest increases in mapped gene coverage following TPA treatment. In silico analysis identified distinct EVs miRNA–gene interaction profiles, with VEGFA emerging as a recurrent predicted target. These results demonstrate that stemness-targeted modulation quantitatively reprograms EVs miRNA cargo in a cell-type-dependent manner, reshaping vesicle-mediated signaling networks in sarcoma. Full article

MASH is a progressive liver disease closely associated with cellular senescence, which is present in more than 80% of hepatocytes in patients who develop hepatocellular carcinoma (HCC). Although MASH affects both sexes, the incidence of MASH-related HCC is two to four times higher in males. Our group has previously described two apoptotic switches during MASH progression and HCC development, implicating the ATP1A1 signalosome in the late switch. Here, we investigated the role of ATP1A1 and sex-specific differences in the early apoptotic switch during preclinical MASH progression. Male and female C57BL/6J mice (7 weeks old) were fed normal mouse chow (NMC) or a high-fat diet (HFD) for 12, 24, or 48 weeks (n = 5/sex/group). Total body weight (TBW) and body composition were assessed by serial measurement and echo-MRI. Plasma was analyzed by non-targeted metabolomics and glutathione profiling using LC-MS/MS. NAFLD activity scores (NAS), hepatic senescence, and apoptosis were quantified in liver tissue. Statistical analyses were performed using GraphPad Prism and R. Males gained greater TBW and lean and fat mass than females (p < 0.05). At 24 W, males demonstrated higher GSH:GSSG ratios and lower ophthalmate levels than females (p < 0.05), consistent with altered redox balance. HFD-fed females showed increased succinic and deoxycholic acid levels, whereas males exhibited higher butyric acid levels across all time points (p < 0.05). Males had a higher mTOR 1 expression at 24 W and P53 at 12 W compared to females on HFD, but a lower Grb2 expression at 24 W (p < 0.05). By 24 W, males had lower fibrosis scores and reduced apoptotic activity compared with females (p < 0.05), despite similar levels of cellular senescence. The expression of ATP1A1, survivin, and SMAC did not differ by sex or diet, although an upregulation trend in both ATP1A1 and survivin was noted in the male-HFD group. There is sexual dimorphism in the response to HFD during the transition from senescence to the apoptosis-first apoptotic switch in MASH progression. Full article

Approximately 40% of women start pregnancy with overweight or obesity, and around 70% retain weight in the postpartum period (PP). Obesity is related to low-grade systemic inflammation, primarily driven by the secretome of white adipose tissue (WAT), which includes dysfunctional adipocytes and immune cells that infiltrate WAT, releasing pro-inflammatory signals into the circulation. In women with obesity, the mammary gland undergoes structural and endocrine changes, such as reduced prolactin secretion, fewer mammary gland branches, and a higher abundance of adipocytes in mammary fat pad, which have not been studied under this condition. Maternal obesity during lactation also alters the composition of breast milk, promoting pro-inflammatory characteristics. The endocannabinoid system (ECS) is hyperactive in obesity, contributing to metabolic inflammation. Its primary receptors, cannabinoids 1 and 2, are expressed in the mammary gland and implicated in inflammation and weight gain. Endocannabinoids (ECs), the main ECS ligands, are typically not released into the bloodstream; however, their increased levels in obesity suggest upregulation in peripheral tissues. ECs are also present in breast milk, where their higher concentrations in women with obesity may influence infant food intake. Full article

Background and Clinical Significance: Fibrolipoma is an uncommon histological variant of lipoma characterized by mature adipose tissue with a significant fibrous component. Intraoral lipomas are rare (only about 1–4% of all lipomas) and lipomas arising in the buccal fat pad (buccal space) are particularly uncommon. Case Presentation: A 47-year-old male presented with a painless, slowly enlarging swelling in the left cheek region. Physical examination revealed a soft, non-tender mass in the buccal space, causing mild bulging of the cheek. Contrast-enhanced computed tomography and magnetic resonance imaging demonstrated a well-circumscribed lesion within the left buccal fat pad suggestive of a lipoma. The tumor was excised entirely via an intraoral approach under general anesthesia. Histopathological examination showed lobules of mature adipocytes interspersed with dense fibrous connective septa consistent with a diagnosis of a fibrolipoma. The postoperative course was uneventful. Conclusions: This case highlights that fibrolipoma, while rare in the maxillofacial region, should be included in the differential diagnosis of buccal space tumors. Imaging studies can aid in identifying the fatty nature and extent of such lesions, but definitive diagnosis relies on histopathology. The buccal fat pad’s anatomy allows an intraoral surgical approach in appropriate cases, providing direct access and excellent cosmetic outcomes. Complete excision is curative in benign fibrolipomas, and careful surgical technique prevents injury to adjacent structures. Full article

Milk production and quality are increasingly affected worldwide by rising ambient temperatures associated with climate change, with heat stress (HS) representing one of the major environmental challenges for dairy cattle. HS alters physiological and metabolic processes, leading to significant changes in milk composition, particularly in regions exposed to prolonged summer heat. The Temperature–Humidity Index (THI) is widely used to assess the degree of thermal discomfort and its impact on dairy performance. This study investigated the effects of heat stress on milk quality parameters in a dairy herd managed under identical conditions, comprising Romanian Black Spotted (RBS, Holstein strain) and Romanian Spotted (RS, Simmental strain) cows. Descriptive statistics were performed using the SAVC for Windows program, while differences between means were evaluated using the t-test in GraphPad Prism 9. Milk quality traits were significantly affected when THI values exceeded 73, with a consistent decline observed from early summer onwards. In the RBS breed, milk protein content decreased significantly compared with spring values, reaching 3.25% (p < 0.0001) in 2023 and 3.35% (p < 0.01) in 2024. Similar trends were recorded in the RS breed, with minimum protein values of 3.10% (p < 0.0001) and 3.19% (p < 0.0001). Fat content, casein concentration, and milk urea levels also showed highly significant HS-related changes (p < 0.0001). Overall, heat stress negatively affected milk quality, while the RS breed appears less affected under the studied conditions than the RBS breed. Full article

Background/Objectives: Immature watermelon (WM) rind contains higher levels of citrulline and potassium than mature fruit and may exert diuretic and metabolic benefits. This study aimed to evaluate the anti-obesity and diuretic effects of WM and salt-treated watermelon rind extract (WMS) in high-fat diet (HFD)-induced obese mice, focusing on changes in lipid metabolism, sodium handling, and tissue-level alterations. Methods: Citrulline concentrations in WM and WMS were quantified using high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Four-week-old male C57BL/6 mice were fed an HFD for 6 weeks and subsequently administered WM (380 mg/kg) or WMS (380 mg/kg) orally for an additional 6 weeks. Body weight, food intake, organ and fat-pad weights, serum biochemical markers, and sodium (Na⁺) levels were measured. Histopathological analyses of liver and epididymal adipose tissue were performed to assess non-alcoholic steatohepatitis (NASH) scores and adipocyte morphology. Results: WM and WMS contained citrulline at levels substantially higher than those reported for mature watermelons. Both treatments significantly reduced body weight, liver weight, and epididymal fat mass compared with the HFD control. Serum total cholesterol and triglyceride levels were lowered in the WM- and WMS-treated groups. Serum Na⁺ concentrations increased by 43.2 ± 7.6% in WM-treated mice and 21.5 ± 6.6% in WMS-treated mice, suggesting enhanced sodium handling. Histological assessment revealed reduced NASH scores and smaller adipocyte sizes in both groups. These improvements are consistent with the known diuretic and metabolic actions of citrulline and potassium. Conclusions: WM and WMS exhibit significant anti-obesity and diuretic effects in HFD-induced obese mice. Their combined actions on sodium excretion, lipid metabolism, and adipose tissue remodeling suggest that immature watermelon rind extracts may serve as promising natural agents for preventing obesity and related metabolic dysfunction. Full article

Osteoarthritis (OA) is a debilitating joint disease affecting over 500 million people globally, characterized by cartilage degradation, chronic pain, and failed tissue repair. Neurogenic inflammation, driven by neuropeptides including Substance P (SP) and calcitonin gene-related peptide (CGRP), plays a key role in the pathogenesis of OA. This study explores the therapeutic potential of extracellular vesicles (EVs) derived from infrapatellar fat pad mesenchymal stem/stromal cells (IFP-MSCs) transduced with CGRP antagonist CGRP_8-37 (aCGRP IFP-MSC EVs). These EVs are enriched in anti-inflammatory miRNAs and proteins, and they express neprilysin (CD10), enabling SP degradation. Herein, several LncRNAs were identified, which have been known to interact with miRNAs that affect the knee joint homeostasis. Specifically, 11 LncRNAs (ZFAS1, EMX2OS, HOTAIRM1, RPS6KA2-AS1, DANCR, LINC-ROR, GACAT1, GNAS-AS1, HAR1A, OIP5-AS1, TERC) interact with miRNAs that promote cell proliferation, prevent apoptosis, and preserve homeostasis. In vitro, aCGRP IFP-MSC EVs downregulated pro-inflammatory markers (TNF, TLR4, MAPK8) in dorsal root ganglia and promoted chondrocyte gene expression consistent with anabolism and matrix remodeling. In vivo, intra-articular EV delivery attenuated pain behaviors, preserved the cartilage structure, restored PRG4+ stem/progenitor cell localization, and trended toward reduced SP levels. Histological analysis confirmed improved collagen organization and reduced matrix degradation. These findings suggest that aCGRP IFP-MSC EVs exert multimodal effects on neuroinflammation, cartilage regeneration, and joint homeostasis. This cell-free, gene-enhanced EV therapy offers a promising disease-modifying strategy for the treatment of OA, with the potential to address both structural changes and chronic pain associated with this disease. Full article

Introduction and Objectives: The thickness of the plantar fat pad (PFP) beneath the metatarsal heads may play a protective role in preventing forefoot disorders such as metatarsalgia. However, reference values for plantar adipose tissue thickness in this region among healthy individuals are currently unavailable. Therefore, the aim of this study was to determine, by means of ultrasound imaging, the thickness of the PFP beneath the five metatarsal heads and to analyze its possible relationship with body mass index (BMI). Materials and Methods: Thirty-five young adults (17 males and 18 females) with neutral feet, free from deformities or pain, participated in the study. Using a VINNO E35 ultrasound device, the thickness of the PFP beneath each of the five metatarsal heads was quantified. A linear transducer was positioned longitudinally along the axis of each metatarsal. The distance between the dermis and the flexor tendon was measured from the second to the fifth metatarsal heads, and from the fibular sesamoid for the first metatarsal head. Results: The central forefoot showed the greatest PFP thickness (2nd metatarsal head, 7.1 ± 0.9 mm; 3rd metatarsal head, 6.9 ± 0.9 mm). No significant differences in PFP thickness were found between sexes. However, a positive correlation was observed between BMI and PFP thickness at the fourth metatarsal head (r = 0.358, p = 0.035). Conclusions: The study demonstrated greater PFP thickness beneath the second and third metatarsal heads, with no significant sex-related differences. These findings indicate a consistent anatomical pattern independent of sex in young, healthy individuals. Moreover, a moderate influence of BMI was identified at the fourth metatarsal head, which could represent a potential protective mechanism against forefoot overload. Full article