Search Results (350)

Bone-related defects present a key challenge in orthopaedics. The current gold standard, autografts, poses significant limitations, such as donor site morbidity, limited supply, and poor morphological adaptability. This study investigates the potential of scaffold geometry to induce osteogenic differentiation of human adipose-derived stem cells (hADSCs) through mechanotransduction, without the use of chemical inducers. Four distinct poly-(L)-lactic acid (PLA) scaffold architectures—Traditional Cross (Tc), Triangle (T), Diamond (D), and Gyroid (G)—were fabricated using fused filament fabrication (FFF) 3D printing. hADSCs were cultured on these scaffolds, and their response was evaluated utilising an alkaline phosphatase (ALP) assay, immunofluorescence, and extensive proteomic analyses. The results showed the D scaffold to have the highest ALP activity, followed by Tc. Proteomics results showed that more than 1200 proteins were identified in each scaffold with unique proteins expressed in each scaffold, respectively Tc—204, T—194, D—244, and G—216. Bioinformatics analysis revealed structures with complex curvature to have an increased expression of proteins involved in mid- to late-stage osteogenesis signalling and differentiation pathways, while the Tc scaffold induced an increased expression of signalling and differentiation pathways pertaining to angiogenesis and early osteogenesis. Full article

Background/Objectives: Estrogen deficiency contributes to dyslipidemia and visceral adiposity, increasing cardiovascular risk in postmenopausal women. Sargassum fulvellum (Sf), a brown seaweed rich in bioactive compounds, possesses lipid-regulating properties that may be enhanced by lactic acid bacteria fermentation. This study aimed to evaluate the effects of fermented S. fulvellum (SfLlLm), prepared using Lactococcus lactis and Leuconostoc mesenteroides, on lipid metabolism and adipose tissue remodeling in an ovariectomized (OVX) mouse model of estrogen deficiency. Methods: Female C57BL/6 mice underwent ovariectomy and were fed an AIN-76A diet supplemented with either unfermented Sf or SfLlLm for eight weeks. Sham-operated and 17β-estradiol-treated OVX groups served as controls. Serum lipid levels—total cholesterol, triglycerides, LDL-C, and HDL-C—were assessed, and histological analysis of visceral adipose tissue was conducted to evaluate adipocyte morphology. Results: OVX-induced estrogen deficiency led to increased total cholesterol, triglycerides, and LDL-C, along with hypertrophic changes in visceral adipocytes. Supplementation with fermented Sargassum fulvellum (SfLlLm) markedly improved these parameters, reducing total cholesterol by 6.7%, triglycerides by 9.3%, and LDL-C by 52.9%, while increasing HDL-C by 17.5% compared to the OVX controls. SfLlLm also normalized visceral adipocyte size and distribution. These effects were comparable to or exceeded those of 17β-estradiol treatment. Conclusions: Fermented SfLlLm ameliorated dyslipidemia and visceral adiposity under estrogen-deficient conditions. These findings support its potential as a functional dietary intervention for managing postmenopausal lipid disorders and associated metabolic complications. Full article

Background and Objectives: In recent years, there has been growing interest in the production of ingredients rich in dietary fiber and antioxidants, such as green banana flours. This study evaluated the effect of consumption of mixed green banana pulp (PF) and peel (PeF) flours on the body weight gain, adiposity, lipid profile, and intestinal morphology of Wistar rats. Methods: Male young rats were divided into four groups (n = 8) that received a standard diet (SD), or one of the following three test diets: M1 (SD + 90% PF/10% PeF), M2 (SD + 80% PF/20% PeF), or P (SD + 100% PF) for 28 days. Results: Rats from M1, M2, and P groups showed reduced body weight gain and adiposity and had lower contents of total cholesterol, LDL-c, VLDL-c, and triglycerides. Animals from M1 and M2 groups had an increase in cecum weight, fecal moisture, acetic acid concentration, and crypt depth and reduced fecal pH. Moreover, consumption of the M1, M2, and P diets increased the expression of proteins involved in intestinal functionality. Significant negative correlations were observed between consumption of resistant starch and soluble dietary fiber, from the flours, and weight gain (r = −0.538 and r = −0.538, respectively), body adiposity (r = −0.780 and r = −0.767, respectively), total cholesterol (r = −0.789 and r = −0.800, respectively), and triglycerides (r = −0.790 and r = −0.786, respectively). Conclusions: Mixed green banana pulp and peel flour proved to be a viable alternative as a food ingredient that can promote weight loss, improve lipid profile and intestinal morphology, and minimize post-harvest losses. Full article

Background: The most common female endocrinopathy is polycystic ovary syndrome (PCOS), affecting 10–20% of women of reproductive age. It is associated with a wide range of hormonal and biochemical abnormalities and long-term metabolic and cardiovascular risks. It is characterized by infertility due to chronic anovulation, hyperandrogenism, polycystic ovarian morphology, and is often associated with insulin resistance (IR) and obesity. Hyperinsulinemia further increases androgen production and reduces sex hormone-binding globulin (SHBG) levels, thereby aggravating symptoms. In addition, vitamin D deficiency is often present in PCOS patients, and increasing evidence suggests that it may also be associated with insulin resistance and hyperandrogenism. Objective: This study aimed to evaluate the relationships between insulin resistance, vitamin D deficiency, body mass index (BMI), and androgen levels in women with PCOS. Method: A cross-sectional study was conducted in which data from 195 women diagnosed with PCOS and not yet receiving therapy at a gynecologic endocrinology unit of a university-based tertiary clinical center, between 2019 and 2024, were analyzed. The parameters recorded were age, body mass index (BMI), 25(OH) vitamin D levels, androgen hormone levels (testosterone, androstenedione), glucose-insulin responses during a 3-point oral glucose tolerance test (OGTT). Statistical analyses, including linear regression, Pearson, and Spearman correlation tests were used to assess associations between variables. Results: The mean age of the patients was 24.8 years (18–42), and the mean BMI was 30.6 kg/m² (17–51). Vitamin D deficiency was observed in 84.1% of patients, hyperandrogenism in 45.8%, and insulin resistance in 44.5%. A significant inverse correlation was found between BMI and vitamin D levels (r = −0.31, p =< 0.01) indicating that higher BMI is associated with lower vitamin D status. Similarly, BMI also showed a significant negative correlation with SHBG levels (r = –0.45, p < 0.01), suggesting that increasing body weight is linked to reduced SHBG concentrations. In addition, BMI was significantly positively correlated with 2 h insulin levels (r = 0.43, p =< 0.01) and with testosterone levels (r = 0.21, p = 0.01). These findings suggest that increased adiposity intensifies insulin resistance and is linked to both vitamin D deficiency and elevated androgen levels. Moreover, the combination of hyperinsulinemia and low vitamin D further disrupts hormonal balance by promoting ovarian androgen production and decreasing SHBG levels, thereby increasing the bioavailability of testosterone. A significant inverse correlation was found between vitamin D levels and 2 h insulin levels (r = −0.28, p =< 0.01), indicating that lower vitamin D status is associated with increased insulin resistance. Furthermore, 2 h insulin levels showed a significant positive correlation with testosterone levels (r = 0.32, p =< 0.01), suggesting that greater insulin resistance is linked to higher androgen production. Additionally, vitamin D levels were inversely correlated with testosterone (r = −0.18, p = 0.02), demonstrating that a lower vitamin D status may further contribute to the hyperandrogenic environment. Vitamin D levels also showed a significant positive correlation with SHBG concentrations (r = 0.29, p < 0.01), indicating that a higher vitamin D status may be associated with increased SHBG levels. In contrast, 2 h insulin levels were inversely correlated with SHBG (r = −0.43, p < 0.01), reflecting the suppressive effect of hyperinsulinemia on SHBG production. Conclusions: Insulin resistance, BMI, and vitamin D deficiency are closely related to each other and to the severity of PCOS, which is confirmed by the correlations with androgen levels. The revealed relationships draw attention to the special importance of vitamin D supplementation and the correction of carbohydrate metabolism in alleviating the symptoms of the disease and reducing long-term health risks. Full article

The advent of effective antiretroviral therapy in the mid-1990s, which successfully prevented the progression to AIDS in people living with HIV (PLWH), was associated with the appearance of the so-called HIV-associated lipodystrophy. This condition involved subcutaneous fat atrophy; abdominal fat hypertrophy; and, in some cases, lipomatosis. It was also associated with systemic metabolic disturbances, primarily insulin resistance and dyslipidemia. Following the replacement of certain antiretroviral drugs, particularly the thymidine-analog reverse transcriptase inhibitors stavudine and zidovudine, with less toxic alternatives, the incidences of lipoatrophy and lipomatosis significantly declined. However, lipodystrophy resulting from first-generation antiretroviral therapy does not always resolve after switching to newer agents. Although the widespread use of modern antiretroviral drugs—especially integrase strand transfer inhibitors and non-lipoatrophic reverse transcriptase inhibitors such as tenofovir alafenamide—has reduced the incidences of severe forms of lipodystrophy, these regimens are not entirely free of adipose tissue-related effects. Notably, they are associated with weight gain that resembles common obesity and can have adverse cardiometabolic consequences. Recent evidence also suggests the hypertrophy of specific fat depots, such as epicardial and perivascular adipose tissue, in PLWH on last-generation treatments, potentially contributing to increased cardiovascular risk. This evolving landscape underscores the persistent vulnerability of PLWH to adipose tissue alterations. While these morphological changes may not be as pronounced as those seen in classic HIV-associated lipodystrophy, they can still pose significant health risks. The continued optimization of treatment regimens and the vigilant monitoring of adipose tissue alterations and metabolic status remain essential strategies to improve the health of PLWH. Full article

The aim of this study is to investigate the physiological characteristics and regulatory mechanisms of porcine intramuscular fat (IMF), subcutaneous fat (take back fat (BF), for example), and visceral fat (take perienteric fat (PF), for example) to address the challenge of optimizing meat quality without excessive fat deposition. Many improved breed pigs have fast growth rates, high lean meat rates, and low subcutaneous fat deposits, but they also have low IMF content, resulting in poor meat quality. There is usually a positive correlation between intramuscular fat and subcutaneous fat deposits. This study selected eight-month-old female Tibetan pigs as experimental subjects. After slaughter, fat samples were collected. Histological differences in adipocyte morphology were observed via hematoxylin–eosin (HE) staining of tissue sections, and phenotypic characteristics of different adipose tissues were analyzed through fatty acid composition determination. Transcriptome sequencing and untargeted metabolomics were employed to perform pairwise comparisons between different fatty tissues to identify differentially expressed genes and metabolites. A siRNA interference model was constructed and combined with Oil Red O staining and lipid droplet optical density measurement to investigate the regulatory role of WNT16 in adipocyte differentiation. Comparative analysis of phenotypic and fatty acid composition differences in adipocytes from different locations revealed that IMF adipocytes have significantly smaller areas and diameters compared to other fat depots and contain higher levels of monounsaturated fatty acids. Integrated transcriptomic and metabolomic analyses identified differential expression of WNT16 and L-tyrosine, both of which are involved in the melanogenesis pathway. Functional validation showed that inhibiting WNT16 in porcine preadipocytes downregulated adipogenic regulators and reduced lipid droplet accumulation. This cross-level regulatory mechanism of “phenotype detection–multi-omics analysis–gene function research” highlighted WNT16 as a potential key regulator of site-specific fat deposition, providing new molecular targets for optimizing meat quality through nutritional regulation and genetic modification. Full article

Skin aging is mostly caused by the accumulation of reactive oxygen species (ROS) that lead to cellular dysfunction. One promising therapy for skin aging is the secretome product of adipose tissue mesenchymal stem cells (AT-MSCs). L-ascorbic acid (LAA) is an essential molecule for preventing oxidative stress as an external antioxidant agent and has been used in chemical therapy for skin aging. In this study, we evaluated the effects of LAA on cell morphology, the number of cells, cell viability, and the paracrine secretion of preconditioned AT-MSCs in in vitro culture with LAA in 100 and 200 µg/mL compared with an untreated culture with LAA as a control. LAA supplementation in both concentrations improved the morphology of cells without affecting the cell viability. However, there was no significant improvement in the number of cells even though the trend showed an enhancement of the number of cells. The total protein of the secretome decreased in the LAA preconditioning group. However, preconditioning AT-MSCs in in vitro culture with LAA improved the levels of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1), and interleukin 6 (IL-6) which are essential proteins for skin aging in regulating ROS. Full article

Electrospun collagen-based fibrous mats are of increasing interest for cell culture, regenerative medicine, and tissue engineering. The focus of this investigation is on the assessment of the electrospinning ability of bovine split hide collagen (BSHC), the effect of glycosaminoglycan (GAG) incorporation on the mats’ structural morphology, and the impact on the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hAD-MSCs). Electrospun mats were prepared using benign and fluoroalcohol solutions of BSHC and BSHC/GAGs under varied operation conditions. SEM observations and analysis were employed to characterize the structural morphology of the mats. Several parameters were used to evaluate the hAD-MSC behavior: cytotoxicity, cell morphology, cell number and spreading area, cytoskeleton, focal adhesion contacts, and cell proliferation. Electrospinning using benign solvents was impossible. However, fiber mats were successfully prepared from hexafluoropropanol (HFP) solutions. Different structural morphologies and fiber diameters of the electrospun mats were observed depending on the composition and concentration of the electrospinning solutions. Both BSHC and BSHC/GAG mats supported the in vitro adhesion, growth, and differentiation of hAD-MSCs, with some variations based on their composition and structural morphology. The absence of cytotoxicity and the good hAD-MSC adhesiveness make them promising substrates for cell adhesion, proliferation, and further stem cell differentiation. Full article

A platform of two-component cross-linked hydrogel (cGEL) based on gelatinous peptides and anhydride-containing cross-linkers (oPNMA, oPDMA) is extended for use in peripheral nerve regeneration. Hybrid composites with bio-/chemical cues for enhanced biophysical and biochemical properties were fabricated by covalently grafting small molecular, heterobifunctional amines including the nerve growth factor mimetic LM11A-31 to the oligomeric cross-linkers prior to hydrogel formation. The cytocompatibility and growth-supportive conditions within the matrix are confirmed for pristine and modified hydrogels using L929 mouse fibroblasts and human adipose-derived stem cells (hASCs). For hASCs, cell behavior depends on the type of cross-linker and integrated amine. In a subsequent step, neonatal rat Schwann cells (SCs) are seeded on pristine and functionalized cGEL to investigate the materials’ capabilities to support SC growth and morphology. Within all formulations, cell viability, adherence, and cell extension are maintained though the cell elongation and orientation vary compared to the two-dimensional control. It is possible to merge adjustable two-component hydrogels with amines as biochemical signals, leading to improved nervous cell proliferation and activity. This indicates the potential of tunable bioactive cGEL as biomaterials in nerve implants, suggesting their use as a foundational component for nerve conduits. Full article

The use of entomopathogenic fungi (EPF), such as Cordyceps javanica, to reduce insect pest populations is gaining traction since it is an environmentally safe approach that can control many pests at different life stages. Here, we focus on the histopathology of the coffee berry borer, Hypothenemus hampei, infected by C. javanica. Morphological observation revealed that C. javanica conidia germinated within 12 h following inoculation according to light microscopic and ultrastructural levels. The fungus thoroughly penetrated the fat body and muscular tissue between 84 and 120 h post-inoculation. Transmission electron microscopy (TEM) confirmed the hyphal invasion of the cuticle at 12 h post-inoculation, with progressive tissue disruption and organelle degeneration, especially mitochondria and rough endoplasmic reticulum in adipocytes. All organelles were completely degenerated at 96 h post-inoculation. There was evidence of a connection between C. javanica activity and the coffee berry borer that might cause histopathological changes in the host defense against the pathogen, pointing to increased mortality and potential control of coffee berry borer in natural populations. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) confirmed that apoptotic cells were slightly increased in the adipose tissue and integument of the coffee berry borer. The ability of C. javanica to fatally infect the coffee berry borer suggests that it could be deployed as a biological control agent in the field. Full article

Background/Objectives: Wheat gluten intolerance increases intestinal permeability, triggering inflammation that may directly affect liver function and compromise metabolic health. Methods: Male Wistar rats (n = 50) aged 21 days were divided into five groups (n = 10) based on dietary gluten levels over 100 days: G0 (0%), G14 (14%), G42 (42%), G70 (70%), and G70/0 (70% for the first 70 days, then 0% until euthanasia). At 121 days, the animals were weighed and euthanized, and blood samples were collected for biochemical analyses. Adipose tissue deposits and the liver were excised and weighed. Liver lobes were isolated and fixed for morphological and morphometric analysis of hepatocytes, tissue glycogen percentage, and intracellular lipid assessment. Results: The hepatic oxidative status was evaluated. The ingestion of diets with excess gluten (70%) increased final body mass and reduced liver mass, though it did not alter the adiposity index. Cholesterol, triglycerides, and myeloperoxidase enzyme activity exhibited distinct patterns across all groups. Conclusions: Elevated gluten levels increased oxidative stress and altered tissue hepatic morphology and morphometry. Full article

Liaoning cashmere goats is a dual-purpose breed valued for premium cashmere fiber and meat yields, and there is currently a lack of optimized strategies for meat quality, including skeletal muscle development and lipid partitioning. This investigation systematically examines how melatonin administration modulates gastrointestinal microbiota and antioxidant capacity to concurrently enhance skeletal muscle hypertrophy and redirect lipid deposition patterns, ultimately improving meat quality and carcass traits in Liaoning cashmere goats. Thirty female half-sibling kids were randomized into control and melatonin-treated groups (2 mg/kg live weight with subcutaneous implants). Postmortem analyses at 8 months assessed carcass traits, meat quality, muscle histology, plasma metabolites, and gut microbiota (16S rRNA sequencing). Melatonin supplementation decreased visceral adiposity (perirenal, omental, and mesenteric fat depots with a p < 0.05) while inducing muscle fiber hypertrophy (longissimus thoracis et lumborum (LTL) and biceps femoris (BF) with p < 0.05). The melatonin-treated group demonstrated elevated postmortem pH₂₄h values, attenuated muscle drip loss, enhanced intramuscular protein deposition, and improved systemic antioxidant status (characterized by increased catalase and glutathione levels with concomitant reduction in malondialdehyde with p < 0.05). Melatonin reshaped gut microbiota, increasing α-diversity (p < 0.05) and enriching beneficial genera (Prevotella, Romboutsia, and Akkermansia), while suppressing lipogenic Desulfovibrio populations, and concomitant with improved intestinal morphology as evidenced by elevated villus height-to-crypt depth ratios. These findings establish that melatonin-mediated gastrointestinal microbiota remodeling drives anabolic muscle protein synthesis while optimizing fat deposition, providing a scientifically grounded strategy to enhance meat quality. Full article

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligoanovulation, and polycystic ovarian morphology. Despite its classification as a reproductive disorder, PCOS is closely associated with metabolic dysregulation, including insulin resistance and obesity. An ideal animal model for PCOS should replicate both reproductive and metabolic features of the condition. In this study, we compared two widely used postnatal PCOS models (letrozole and estradiol valerate [EV]) administered alone or in combination with a high-fat diet (HFD), assessing their ability to induce both the reproductive and metabolic features. Letrozole treatment led to significant weight gain and increased visceral adiposity, effects that were amplified by HFD. Conversely, EV treatment showed a tendency toward reduced body mass. While neither model significantly altered fasting glucose levels, letrozole combined with HFD impaired glucose tolerance, supporting its role in metabolic dysfunction. Hyperandrogenism was more consistently induced by letrozole compared to EV, aligning with clinical PCOS phenotypes. Both treatments disrupted estrous cyclicity and induced polycystic ovarian morphology, though metabolic disturbances were more pronounced in the letrozole model. These findings suggest that letrozole, particularly in combination with HFD, provides a more consistent model for studying both the reproductive and metabolic facets of PCOS. Full article

Obesity is a growing global health concern, contributing to diseases such as cancer, autoimmune disorders, and neurodegenerative conditions. Adipose tissue dysfunction, characterized by abnormal adipokine secretion and chronic inflammation, plays a key role in these conditions. Adipose-derived extracellular vesicles (ADEVs) have emerged as critical mediators in obesity-related diseases. However, the study of mature adipocyte-derived EVs (mAdipo-EVs) is limited due to the short lifespan of mature adipocytes in culture, low EV yields, and the low abundance of these EV subpopulations in the circulation. Additionally, most studies rely on rodent models, which have differences in adipose tissue biology compared to humans. To overcome these challenges, we developed a standardized approach for differentiating human preadipocytes (preAdipos) into mature differentiated adipocytes (difAdipos), which produce high-yield, human adipocyte EVs (Adipo-EVs). Using visceral adipose tissue from bariatric surgical patients, we isolated the stromal vascular fraction (SVF) and differentiated preAdipos into difAdipos. Brightfield microscopy revealed that difAdipos exhibited morphological characteristics comparable to mature adipocytes (mAdipos) directly isolated from visceral adipose tissue, confirming their structural similarity. Additionally, qPCR analysis demonstrated decreased preadipocyte markers and increased mature adipocyte markers, further validating successful differentiation. Functionally, difAdipos exhibited lipolytic activity comparable to mAdipos, supporting their functional resemblance to native adipocytes. We then isolated preAdipo-EVs and difAdipo-EVs using tangential flow filtration and characterized them using bulk and single EV analysis. DifAdipo-EVs displayed classical EV and adipocyte-specific markers, with significant differences in biomarker expression compared to preAdipo-EVs. These findings demonstrate that difAdipos serve as a reliable surrogate for mature adipocytes, offering a consistent and scalable source of adipocyte-derived EVs for studying obesity and its associated disorders. Full article

Aortic aneurysms (AAs), the dilation or widening of the aorta, lead to dissection or rupture with high morbidity and mortality if untreated. AA displays gender disparities in its prevalence, progression and outcomes, with women having worse outcomes and faster aneurysm growth. However, current guidelines do not address gender dimorphism, emphasizing the urgent need for personalized treatment strategies and further research. Perivascular adipose tissue (PVAT), a unique type of fat surrounding blood vessels, plays a critical role in maintaining vasomotor tone and vascular homeostasis, with dysfunction associated with chronic inflammation and vessel-wall remodeling. Indeed, PVAT dysfunction promotes the development of aortic aneurysms, with hormonal and biomechanical factors exacerbating the pathological vascular microenvironment. The sexually dimorphic characteristics of PVAT include morphological, immunological, and hormonally mediated differences. Thus, targeting PVAT-mediated mechanisms may be a promising option for the (gender-specific) therapeutic management of cardiovascular pathologies. This review examines the emerging importance of PVAT in vascular health, its potential therapeutic implications for AA, and identifies gaps in the current state of research. Full article