Search Results (19,867)

The artichoke (Cynara cardunculus L. subsp. scolymus) is an endemic perennial plant of the Mediterranean area commonly consumed as food. It is known since ancient times for its beneficial properties for human health, among which its antioxidant activity due to polyphenolics stands out. In the frame of our ongoing studies aiming to highlight the biodiversity and the chemodiversity of natural resources, we investigated the phenolic and saponin content of the cultivar “Carciofo di Procida” collected at Procida, an island of the Gulf of Naples (Italy). Along with the edible part of the immature flower, we included in our analyses the stem and the external bracts, generally discarded for food consuming or industrial preparations. The LCMS quali-quantitative profiling of polyphenols (including anthocyanins) and cynarasaponins of this cultivar is reported for the first time. In addition to antioxidant properties, we observed a significant cytotoxic activity due to extracts from external bracts against human neuroblastoma SH-SY5Y cell lines with 43% of cell viability, after 24 h from the treatment (50 μg/mL), and less potent but appreciable effects also against human colorectal adenocarcinoma CaCo-2 cells. This suggests that the different metabolite composition may be responsible for the bioactivity of extracts obtained from specific parts of artichoke and foresees a possible exploitation of the discarded material as a source of beneficial compounds. Full article

Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities. Full article

Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article

Diploid Vaccinium fuscatum is a wild blueberry species with a low chilling requirement, an evergreen growth habit, and soil adaptability to southeast US growing regions. Regardless of its potential to improve the abiotic and biotic resilience of cultivated blueberries, this species has rarely been used for blueberry breeding. One hurdle is the ploidy barrier between diploid V. fuscatum and tetraploid cultivated highbush blueberries. To overcome the ploidy barrier, vegetative shoots micro-propagated from one genotype of V. fuscatum, selected because it grew vigorously in vitro and two southern highbush cultivars, ‘Emerald’ and ‘Rebel,’ were treated with colchicine. While shoot regeneration was severely repressed in ‘Emerald’ and ‘Rebel,’ shoot production from the V. fuscatum clone was not compromised at either 500 µM or 5000 µM colchicine concentrations. Due to the high number of shoots produced in vitro via the V. fuscatum clone shoots of this clone that had an enlarged stem diameter in vitro were subjected to flow cytometer analysis to screen for induced polyploidy. Sixteen synthetic tetraploid V. fuscatum, one synthetic octoploid ‘Emerald,’ and three synthetic octoploid ‘Rebel’ were identified. Growth rates of the polyploid-induced mutants were reduced compared to their respective wildtype controls. The leaf width and length of synthetic tetraploid V. fuscatum and synthetic octoploid ‘Emerald’ was increased compared to the wildtypes, whereas the leaf width and length of synthetic octoploid ‘Rebel’ were reduced compared to the wildtype controls. Significant increases in stem thickness and stomata guard cell length were found in the polyploidy-induced mutant lines compared to the wildtypes. In the meantime, stomata density was reduced in the mutant lines. These morphological changes may improve drought tolerance and photosynthesis in these mutant lines. Synthetic tetraploid V. fuscatum can be used for interspecific hybridization with highbush blueberries to expand the genetic base of cultivated blueberries. Full article

Cell confluence and number are critical indicators for assessing cellular growth status, contributing to disease diagnosis and the development of targeted therapies. Accurate and efficient cell segmentation is essential for quantifying these indicators. However, current segmentation methodologies still encounter significant challenges in addressing multi-scale heterogeneity, poorly delineated boundaries under limited annotation, and the inherent trade-off between computational efficiency and segmentation accuracy. We propose an innovative network architecture. First, a preprocessing pipeline combining contrast-limited adaptive histogram equalization (CLAHE) and Gaussian blur is introduced to balance noise suppression and local contrast enhancement. Second, a bidirectional feature pyramid network (BiFPN) is incorporated, leveraging cross-scale feature calibration to enhance multi-scale cell recognition. Third, adaptive kernel convolution (AKConv) is developed to capture the heterogeneous spatial distribution of glioma stem cells (GSCs) through dynamic kernel deformation, improving boundary segmentation while reducing model complexity. Finally, a probability density-guided non-maximum suppression (Soft-NMS) algorithm is proposed to alleviate cell under-detection. Experimental results demonstrate that the model achieves 95.7% mAP50 (box) and 95% mAP50 (mask) on the GSCs dataset with an inference speed of 38 frames per second. Moreover, it simultaneously supports dual-modality output for cell confluence assessment and precise counting, providing a reliable automated tool for tumor microenvironment research. Full article

Background: Mesenchymal stem cells (MSCs) are a promising tool in regenerative medicine due to their ability to secrete paracrine factors that modulate tissue repair. Extracellular vesicles (EVs) released by MSCs contain bioactive molecules (e.g., mRNAs, miRNAs, proteins) and play a key role in intercellular communication. Methods: This study compared the transcriptomic profiles (mRNA and miRNA) of equine MSCs derived from adipose tissue (AT-MSCs), bone marrow (BM-MSCs), and ovarian fibroblasts (as a differentiated control). Additionally, miRNAs present in EVs secreted by these cells were characterized using next-generation sequencing. Results: All cell types met ISCT criteria for MSCs, including CD90 expression, lack of MHC II, trilineage differentiation, and adherence. EVs were isolated using ultracentrifugation and validated with nanoparticle tracking analysis and flow cytometry (CD63, CD81). Differential expression analysis revealed distinct mRNA and miRNA profiles across cell types and their secreted EVs, correlating with tissue origin. BM-MSCs showed unique regulation of genes linked to early development and osteogenesis. EVs contained diverse RNA species, including miRNA, mRNA, lncRNA, rRNA, and others. In total, 227 and 256 mature miRNAs were detected in BM-MSCs and AT-MSCs, respectively, including two novel miRNAs per MSC type. Fibroblasts expressed 209 mature miRNAs, including one novel miRNA also found in MSCs. Compared to fibroblasts, 60 and 92 differentially expressed miRNAs were identified in AT-MSCs and BM-MSCs, respectively. Conclusions: The results indicate that MSC tissue origin influences both transcriptomic profiles and EV miRNA content, which may help to interpret their therapeutic potential. Identifying key mRNAs and miRNAs could aid in future optimizing of MSC-based therapies in horses. Full article

The P1104A variant in the TYK2 gene is recognized as the first common monogenic cause of tuberculosis, and recent studies also suggest a potential role in COVID-19 severity. However, its frequency and impact in admixed Latin American populations remain underexplored. Therefore, we investigated the P1104A/TYK2 variant in a cohort comprising 1826 RT-PCR-confirmed COVID-19 patients from Southern Brazil. Cases were stratified by severity into non-severe (n = 1190) and severe (n = 636). Three homozygous individuals were identified—one non-severe and two severe cases—although no statistically significant association with disease severity was observed. The frequency of the C allele in the COVID-19 cohort (2.85%) was significantly higher than in Brazilian population databases, including “DNA do Brasil” (1.81%, p < 0.001) and ABraOM (2.34%, p = 0.03), but lower than in the multi-ancestry gnomAD database (3.71%, p = 0.01), possibly reflecting ancestry bias. We also observed associations between COVID-19 severity and sex (p = 0.003), age (p < 0.001), obesity (p < 0.001), diabetes (p < 0.001), and hypertension (p < 0.001). Future studies in larger and more diverse cohorts are needed to characterize the prevalence of the variant in admixed populations and assess its contribution to COVID-19 susceptibility. Full article

To deliver the most effective cancer treatment, clinicians require rapid and accurate diagnoses that delineate tumor type, stage, and prognosis. Consequently, minimizing the need for repetitive and invasive procedures like biopsies and myelograms, along with their associated risks, is a critical challenge. Non-invasive monitoring offers a promising avenue for tumor detection, screening, and prognostication. While the identification of oncogenes and biomarkers from circulating tumor cells or tissue biopsies is currently standard practice for cancer diagnosis and classification, accumulating evidence underscores the significant role of epigenetics in regulating stem cell fate, including proliferation, self-renewal, and malignant transformation. This highlights the importance of analyzing the methylome, exosomes, and circulating RNA for detecting cellular transformation. The development of diagnostic assays that integrate liquid biopsies with epigenetic analysis holds immense potential for revolutionizing tumor management by enabling rapid, non-invasive diagnosis, real-time monitoring, and personalized treatment decisions. This review covers current studies exploring the use of epigenetic regulation, specifically the methylome and circulating RNA, as diagnostic tools derived from liquid biopsies. This approach shows promise in facilitating the differentiation between primary central nervous system lymphoma and other central nervous system tumors and may enable the detection and monitoring of acute myeloid/lymphoid leukemia. We also discuss the current limitations hindering the rapid clinical translation of these technologies. Full article

The hypothalamus–pituitary–ovarian (HPO) axis orchestrates reproductive functions through intricate neuroendocrine crosstalk. Here, we integrated single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics (ST) to decode the cellular heterogeneity and intercellular communication networks in the reproductive systems of pregnant Mongolian cattle. We retained a total of 6161 high-quality nuclei from the hypothalamus, 14,715 nuclei from the pituitary, and 26,072 nuclei from the ovary, providing a comprehensive cellular atlas across the HPO axis. In the hypothalamus, neurons exhibited synaptic and neuroendocrine specialization, with glutamatergic subtype Glut4 serving as a TGFβ signaling hub to regulate pituitary feedback, while GABAergic GABA1 dominated PRL signaling, likely adapting maternal behavior. Pituitary stem cells dynamically replenished endocrine populations via TGFβ, and lactotrophs formed a PRL–PRLR paracrine network with stem cells, synergizing mammary development. Ovarian luteal cells exhibited steroidogenic specialization and microenvironmental synergy: endothelial cells coregulated TGFβ-driven angiogenesis and immune tolerance, while luteal–stromal PRL–PRLR interactions amplified progesterone synthesis and nutrient support. Granulosa cells (GCs) displayed spatial-functional stratification, with steroidogenic GCs persisting across pseudotime as luteinization precursors, while atretic GCs underwent apoptosis. Spatial mapping revealed GCs’ annular follicular distribution, mediating oocyte–somatic crosstalk, and luteal–endothelial colocalization supporting vascularization. This study unveils pregnancy-specific HPO axis regulation, emphasizing multi-organ crosstalk through TGFβ/PRL pathways and stem cell-driven plasticity, offering insights into reproductive homeostasis and pathologies. Full article

Stoichiometric single crystals of Mn₄Al₁₁ were synthesized from the elements using Sn as a flux. The crystal structure of Mn₄Al₁₁ was investigated using single crystal X-ray diffraction and showed a complex triclinic structure with a relatively small unit cell and interpenetrating networks of Mn and Al atoms. While our results generally agree with the previously reported data in the basic structure features such as triclinic symmetry and structure type, the atomic parameters differ significantly, likely due to different synthetic techniques producing off-stoichiometry or doped crystals used in the previous works. Our structural analysis showed that the view of the Mn substructure as isolated zigzag chains is incomplete. Instead, the Mn chains are coupled in corrugated layers by long Mn-Mn bonds. The high quality of the crystals with the stoichiometric composition also enabled us to study magnetic behavior in great detail and reveal previously unobserved magnetic ordering. Our magnetization measurements showed that Mn₄Al₁₁ is an antiferromagnet with T_N of 65 K. The presence of the maximum above T_N also suggests strong local interactions indicative of low-dimensional magnetic behavior, which likely stems from lowered dimensionality of the Mn substructure. Full article

The growing demand for natural and sustainable skincare products has driven interest in plant-based active ingredients, especially from in vitro cultures. This placebo-controlled study investigated the impact of a facial cream containing 2% Kickxia elatine (L.) Dumort cell suspension culture extract on various skin biophysical parameters. The cream was applied to the cheek once daily for six weeks on 40 healthy female volunteers between the ages of 40 to 49. The evaluated skin parameters including skin hydration, transepidermal water loss (TEWL), erythema intensity (EI), melanin intensity (MI), skin surface pH, and skin structure, wrinkle depth, vascular lesions, and vascular discolouration. The results indicated that significant improvements were observed in skin hydration (from 40.36 to 63.00 AU, p < 0.001) and there was a decrease in TEWL score (14.82 to 11.76 g/h/m², p < 0.001), while the skin surface pH was maintained (14.82 to 11.76 g/h/m², p < 0.001). Moreover, the K. elatine cell extract significantly improved skin structure values (9.23 to 8.50, p = 0.028), reduced vascular lesions (2.72 to 1.54 mm², p = 0.011), and lowered skin discolouration (20.98% to 14.84%, p < 0.001), indicating its moisturising, protective, brightening, and soothing properties. These findings support the potential use of K. elatine cell extract in dermocosmetic formulations targeting dry, sensitive, or ageing skin. Full article

Livestock, poultry, and fisheries play an important economic role in Pakistan’s animal industry. The pet industry is also emerging and contributing to the country’s economy and people’s emotional well-being. This review provides insight into the current challenges and future directions of the animal industry in Pakistan. Livestock, poultry, and fisheries provide an economically beneficial source of milk, meat, and eggs; however, they face challenges such as disease outbreaks, antimicrobial resistance, climate change, natural disasters, and a lack of proper policies. Likewise, humans benefit from companion animals that provide emotional attachment. Moreover, the pet food market has also shown potential growth, contributing to the country’s economy. Due to the close association between animals and humans, both are at risk for infectious disease transmission. Challenges such as the lack of strong animal welfare laws and the increasing number of stray dogs and cats threaten human safety and that of other animals. We highlight current problems and additional approaches to the management of livestock, poultry, fisheries, and pets, which need to be addressed to further advance the animal industry in Pakistan. Full article

Background: Autologous fat grafting is increasingly used in daily clinical practice across various surgical fields, including the treatment of chronic wounds, scars, burns, and non-healing perianal fistulas. Recently, some studies have shown that non-enteric cutaneous fistulas can also benefit from adipose tissue injections, but the efficacy remains unclear. This study aims to systematically review the literature on fat grafting in the context of non-enteric cutaneous fistulas and to assess treatment outcomes. Methods: A comprehensive search of the PubMed/Medline database was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines up to January 2024 without restrictions on the time period or the language of publication. Results: Seven studies meeting the inclusion criteria were analyzed, encompassing 13 patients with non-healing cutaneous fistulas treated with injections of autologous fat. The mean age of the patients was 58 ± 3 years, of which 85% had comorbidities. Fat grafting resulted in complete healing in 92% of the cases, with a mean fistula persistence of 158 days before treatment. Treatment protocols varied among patients, including preparation of the fistulous tract, fat processing techniques, and suturing of the fistulous orifice. Conclusions: The results highlight the potential of autologous fat grafting in promoting tissue regeneration and healing of non-enteric cutaneous fistulas. Standardized protocols are essential to confirm and optimize treatment efficacy and, eventually, improve patient outcomes. Further research with a larger sample size and standardization is needed to confirm fat graft efficacy. Full article

Chemoresistance is a major challenge in the treatment of triple-negative breast cancer (TNBC). Multicellular spheroids are an attractive platform for investigating chemoresistance in TNBC, as they replicate the cues of the tumour microenvironment in vivo. We conducted a comprehensive literature search to summarise the multifactorial and interlinked mechanisms driving chemoresistance in TNBC spheroids. These mechanisms include spatial heterogeneity, hypoxia, extracellular matrix remodelling, tumour–stroma crosstalk, drug efflux, apoptotic resistance, and cancer stem cell signalling. Strategies for overcoming chemoresistance in TNBC spheroids include nanocarrier systems to overcome spatial diffusion limitations, pathway inhibition, and targeting tumour–microenvironment interactions. Despite their advantages, some spheroid models face challenges such as low reproducibility, a lack of heterogeneity, variability in size and shape, limited vascularisation, and constraints in long-term culture. Advanced culturing platforms such as clinostat bioreactors allow for extended culture periods, enabling mature spheroid drug testing. Furthermore, advanced analytical techniques provide spatially resolved spheroid data. These multifactorial and interlinked mechanisms reflect the tumour microenvironment in vivo that spheroids recapitulate, rendering them valuable models for studying chemoresistance. The incorporation of stromal components and advanced analytical workflows will enhance the utility and translational relevance of spheroids as reliable preclinical models for drug discovery in TNBC. Full article