Search Results (1,429)

The efficacy of platelet-rich plasma (PRP) has long been associated with platelet concentration, yet clinical outcomes remain highly variable and frequently inconsistent. This review challenges the assumption that platelet count alone defines PRP efficacy, proposing instead that functional platelet quality and growth-factor bioactivity are equally critical determinants of therapeutic outcomes. Platelets act as carriers of bioactive molecules stored within alpha granules, including growth factors such as platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF), which orchestrate the cellular and molecular events of tissue repair. Variations in donor biology, age, metabolic status, and oxidative stress profoundly influence platelet functionality and growth-factor release. Likewise, centrifugation parameters, temperature control, and activation methods dictate whether these mediators are preserved or prematurely exhausted. Collectively, these findings reveal that platelet number alone cannot predict regenerative potency. The future of PRP standardization requires the integration of platelet quality indices, growth-factor quantification, and patient optimization protocols into clinical practice. By shifting focus from platelet enumeration to bioactivity assessment, regenerative medicine can achieve more consistent, personalized, and scientifically accurate outcomes. Full article

An increasing number of stroke survivors are burdened by persistent disabilities, requiring long-term rehabilitation. However, the extent of functional gain is highly variable, severely impairing patients’ quality of life. This variability highlights a critical gap in current prognostic tools, which rely primarily on clinical and neuroimaging data. The aim of this review is to synthesize the current literature on serum biomarkers in stroke survivors and to evaluate their prognostic value for rehabilitation outcomes. Our synthesis indicates that biomarkers reflecting distinct pathophysiological processes are emerging as key prognostic indicators. Markers of inflammation such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Interleukin-1 beta (IL-1β), and neuro-glial injury, including S100 Calcium-Binding Protein B (S100B), Neuron-Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), and Neurofilament Light Chain (NfL), are consistently associated with poorer functional outcomes. Conversely, markers of neuroplasticity, such as Brain-Derived Neurotrophic Factor (BDNF) and Insulin-like Growth Factor-1 (IGF-1), serve as potential indicators of recovery potential, although their predictive accuracy remains inconsistent across studies. Furthermore, emerging biomarkers of synaptic activity, such as Syntaxin-1a (STX1A) and Synaptosomal-Associated Protein, 25kDa (SNAP-25), and neuromuscular junction integrity, such as C-terminal Agrin Fragment (CAF), offer novel insights into brain–periphery communication, though their clinical utility is still under investigation. While promising, the translation of these biomarkers into clinical practice is hindered by methodological limitations, including assay heterogeneity and lack of large-scale validation. Future standardization of these molecular signatures is a critical step toward implementing precision medicine in stroke rehabilitation. Full article

Transforming growth factor-beta 1 (TGF-β1)-stimulated clone 22 domain (TSC22D) family genes (including TSC22D1-TSC22D4) were identified as transcription factors. It has been demonstrated that they display multiple functions due to proteins’ isoforms, redundancy, and other factors. Formerly, researchers mainly focused on its functions, like controlling cell growth and development, cell apoptosis, and balance of osmotic pressure in vivo. Nowadays, growing evidence indicates that they also play an important role in metabolic regulation and the immune system and are expected to be a new potential target for the treatment of diabetes or obesity. Despite this, it has been shown that TSC22D family genes have an inhibitory effect in multiple tumors. In this review, we significantly synthesized advances in metabolism, showing that TSC22D3 could control lipid accumulation via modulating adipogenesis and adipose differentiation, while TSC22D4 could regulate insulin sensitivity and gluconeogenesis by affecting Akt (serine/threonine kinase, also known as protein kinase B, or PKB) phosphorylation. Moreover, we provide novel insights, including the fact that TSC22D family genes function as a double-edged sword in cancer due to the type of tumor and tumor microenvironment (TME). Full article

Alopecia profoundly impacts psychological well-being and quality of life, yet current therapeutic options such as minoxidil and finasteride exhibit limited efficacy. Fibroblast growth factor 7 (FGF-7), also known as keratinocyte growth factor (KGF), is a paracrine growth factor secreted by dermal papilla cells that specifically activates the epithelial receptor FGFR2b. Receptor engagement triggers multiple downstream signaling cascades, including the MAPK/ERK, PI3K/Akt, and Wnt/β-catenin pathways, promoting keratinocyte proliferation, stem cell activation, and the transition of hair follicles into the anagen phase. Both in vitro and in vivo animal studies consistently demonstrate that FGF-7 accelerates telogen-to-anagen transition and enhances follicular regeneration. FGF-7 acts synergistically with insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) to sustain nutrient delivery and cell proliferation. Human scalp studies further reveal a strong association between the FGF-7/FGFR2b signaling and follicular activity; however, clinical trials remain scarce. Topical application of FGF-7 has demonstrated an excellent safety profile, whereas systemic administration necessitates careful monitoring. Future directions include the development of engineering to extend the systemic half-life, advanced delivery systems, and gene or mRNA-based therapeutic approaches. Thus, the FGF-7/FGFR2b axis is a highly compelling molecular target for next-generation hair regeneration therapies. Full article

The increasing accumulation of plastic debris in aquatic environments has raised concerns about the ecotoxicological effects of polystyrene nanoplastics (PSNPs). This study examined PSNPs toxicity during a critical developmental stage by exposing 15 days post-fertilization (dpf) larvae of blotched snakehead (Channa maculata), an economically important freshwater fish, to PSNPs concentrations of 0.05–20 mg/L for 15 days. Histopathological analysis showed concentration-dependent damage, including hepatocellular vacuolization (5–10 mg/L) and hepatic sinusoidal dilation (20 mg/L) in the liver, alongside intestinal injuries ranging from villus erosion to rupture (5–20 mg/L). Biochemically, PSNPs triggered a biphasic oxidative response, where superoxide dismutase (SOD) and catalase (CAT) activities peaked at 5 mg/L before declining, while malondialdehyde (MDA) levels exhibited an opposite trend. Transcriptomic analysis and Quantitative real-time PCR (qRT-PCR) indicated that PSNPs disrupted growth, energy metabolism, and immune regulation in C. maculata larvae, evidenced by the dysregulation of growth hormone/insulin-like growth factor (GH/IGF) axis genes and up-regulation of immune-related genes. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) identified the heterogeneous nuclear ribonucleoproteins (HNRNP) gene family as hub genes from the key turquoise module, suggesting that PSNPs interfere with RNA processing and post-transcriptional control. In summary, PSNPs caused multi-level toxicity in C. maculata larvae, providing new insights into their ecotoxicological hazards in freshwater ecosystems. Full article

Previous studies have shown that miR-5110 regulates pigmentation by cotargeting melanophilin (MLPH) and WNT family member 1 (WNT1). In order to find the possible molecular mechanism for pigmentation, we examined the mRNA expression profiles in melanocytes of alpaca transfected with miR-5110, inhibitor or negative control (NC) plasmids using high-throughput RNA sequencing. The results showed that a total of 91,976 unigenes were assembled from the reads, among which 13,262 had sequence sizes greater than 2000 nucleotides. According to the KEGG pathway analysis, four pathways related to melanogenesis, the MAPK signaling pathway, Wnt signaling pathway, and cAMP signaling pathway were identified. Compared to the NC, 162 gene were upregulated and 41 genes were downregulated in melanocytes over expressed by miR-5110. The differential expressions of mRNAs Dickkopf 3 (DKK3), premelanosome protein (Pmel), insulin-like growth factor 1 receptor (IGF1R), cyclin-dependent kinase 5 (CDK5), endothelin receptor type B (Ednrb), kit ligand (Kitl), Myc, and S100 were verified using qRT-PCR, which agreed with the results of RNA sequencing. We also verified the differential expressions of mRNAs of some genes in the MAPK signaling pathway using qRT-PCR, which agreed with the results of RNA sequencing. Interestingly, several genes were screened as candidates for the melanogenesis regulated by miR-5110, including Kitl and MAPK-activated protein kinase 3 (MAPKAPK3). These findings provide new insights for further molecular studies on the effects of miR-5110 on the melanogenesis and pigmentation. Full article

The global aging population has led to a rising prevalence of cognitive impairment, posing a significant public health challenge. Resistance training (RT) is a non-pharmacological intervention that has been increasingly investigated for its potential to support cognitive function in older adults. Clinical evidence suggests that RT may be associated with benefits in certain cognitive domains, including memory, executive function, processing speed, and visuospatial ability. However, findings across studies remain heterogeneous, with several trials reporting neutral outcomes. Most intervention studies involve structured RT programs conducted at moderate to high intensity and performed multiple times per week. However, optimal training parameters have not yet been clearly established due to variability in study design and the absence of formal dose–response analyses. Emerging evidence suggests that the cognitive effects of RT may be mediated, at least in part, through muscle–brain axis signaling involving exercise-induced myokines. Factors such as irisin, brain-derived neurotrophic factor, interleukin-6, interleukin-15, and insulin-like growth factor-1 have been implicated in processes related to neuroplasticity, neuroinflammatory regulation, and neurovascular function, primarily based on preclinical and translational research. This review synthesizes current evidence on RT-related molecular mechanisms and clinical findings to provide an integrative perspective on the potential role of resistance training in mitigating age-related cognitive decline. Full article

This study evaluated the effects of replacing corn with defective jujube (DJ) on growth, digestibility, blood biochemical indices, meat performance, and the presence of Alternaria toxin residues in Karakul lambs. Thirty-six lambs were split into groups given 0%, 15%, or 30% DJ, replacing 0%, 45.45%, and 90.91% of corn. The trial lasted 75 days, with 15 days for adaptation and 60 days for measurement. Digestibility for crude protein and ether extract of male lambs increased in the DJ30 group over CON (p < 0.05). High-density lipoprotein decreased in DJ30 (p < 0.01), while triglycerides and total cholesterol in DJ30 dropped (p < 0.05). Blood urea nitrogen and aspartate aminotransferase decreased in DJ15 and DJ30 (p < 0.01). Superoxide dismutase and catalase rose in DJ30 (p < 0.01), while malondialdehyde declined (p < 0.05). Growth hormone and insulin-like growth factor-1 increased in DJ30 (p < 0.01). Feeding DJ did not affect meat production or quality. No Alternaria toxins were detected in rumen, liver, or meat. Feeding 15–30% DJ improved nitrogen utilization, lipid metabolism, and blood antioxidant levels in lambs and reduced the risk of liver damage, while no Alternaria toxin remained in organs. A 30% DJ substitution for corn is a safe strategy for lamb feeding. Full article

Background: Alcohol use disorder (AUD) is associated with chronic heavy or repeated binge alcohol abuse, which can cause alcohol-related brain damage (ARBD) marked by neurobehavioral, cognitive, and motor deficits. The anterior frontal lobe and cerebellar vermis are two of the major targets of ARBD in humans with AUD and in experimental alcohol exposed models. Alcohol’s neurotoxic and neurodegenerative effects include impairments in signaling through insulin and insulin-like growth factor (IGF) pathways that regulate energy metabolism. This human AUD study was inspired by a recent report suggesting that dysfunction of the frontal lobe incretin network in experimental ARBD is linked to known impairments in brain insulin/IGF signaling. Objective: The overarching goal was to investigate whether AUD is associated with dysfunction of the brain’s incretin network, focusing on the cerebellum and frontal lobe. Methods: Fresh frozen postmortem cerebellar vermis and anterior frontal lobe tissues from adult male AUD (n = 6) and control (n = 6) donors were processed for protein extraction. Duplex enzyme-linked immunosorbent assays (ELISAs) were used to assess immunoreactivity to neurofilament light chain (NfL) as a marker of neurodegeneration. A multiplex ELISA was used to measure immunoreactivity to a panel of gut hormones, including incretin polypeptides. Results: AUD was associated with significantly increased NfL immunoreactivity in both the cerebellar vermis and anterior frontal lobe. However, the patterns of AUD-related alterations in gut hormone immunoreactivity differed regionally. AUD reduced pancreatic polypeptide immunoreactivity in the cerebellar vermis, and GIP, GLP-1, leptin, and ghrelin in the frontal lobe. Conclusions: (1) Increased NfL may serve as a useful biomarker of neurodegeneration in AUD. (2) AUD’s adverse effects on neuroendocrine signaling networks differ in the cerebellar vermis and anterior frontal region, although both are significant targets of ARBD. (3) The finding of AUD-associated reductions in frontal lobe GIP and GLP-1 suggests that therapeutic targeting with incretin receptor agonists may help restore energy metabolism and neurobehavioral and cognitive functions linked to their networks. Full article

Background and Objectives: Periodontal disease, characterized by progressive destruction of tooth-supporting tissues, often results in substantial alveolar bone loss, necessitating regenerative interventions such as guided bone regeneration (GBR). Insulin-like growth factor 2 (IGF-2) has emerged as a promising biomolecule for periodontal regeneration because of its osteogenic and immunomodulatory properties. Materials and Methods: A comprehensive literature search was conducted across five electronic databases (Scopus, ScienceDirect, PubMed, Wiley, and EBSCO). Studies examining the use of IGF-2 in periodontal or alveolar bone regeneration, including randomized controlled trials, animal studies, and in vitro experiments, were included. Results: Three studies met the inclusion criteria. In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, along with upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. However, heterogeneity in study designs, protocols, and outcome measures limited direct comparisons. Conclusions: In vitro, IGF-2 was associated with enhanced osteogenic differentiation and mineralization of mesenchymal stem cells, accompanied by upregulation of key osteogenic markers. In animal models, IGF-2 treatment was associated with increased osteogenesis, greater bone volume, and a shift in macrophage polarization toward a less inflammatory phenotype. Full article

The insulin-like growth factor (IGF) axis orchestrates hepatic development, regeneration, and metabolism, yet the roles of individual IGF-binding proteins (IGFBPs) remain incompletely defined. IGFBP-6, a high-affinity, IGF-II-preferring binding protein, has emerged as a context-dependent modulator of IGF bioavailability and cell signaling with additional IGF-independent actions. This review synthesizes current evidence on IGFBP-6 in liver biology and disease. We first outline hepatic expression, regulation, and post-translational processing of IGFBP-6 across development, homeostasis, and injury, and summarize its effects on canonical IGF-II/IGF1R signaling and downstream phosphatidylinositol 3-kinase—protein kinase B (PI3K–AKT) and rat sarcoma—mitogen-activated protein kinase (RAS–MAPK) pathways. We then evaluate experimental and clinical data linking IGFBP-6 to steatotic liver disease, inflammation, and fibrogenesis, including putative roles in hepatocyte stress responses, stellate cell activation, and extracellular matrix remodeling. Finally, we examine IGFBP-6 in primary liver cancers—hepatocellular carcinoma and cholangiocarcinoma—highlighting evidence for tumor-suppressive versus pro-migratory activities, potential crosstalk with hypoxia, Wnt/β-catenin and TGF-β signaling, and interactions with the tumor immune microenvironment. Across conditions, we assess the translational potential of IGFBP-6 as a circulating or tissue biomarker, its utility for patient stratification, and prospects for therapeutic targeting—either by modulating IGF-II sequestration or exploiting IGF-independent mechanisms. We conclude by identifying key knowledge gaps, methodological limitations, and priorities for future studies, including standardized measurement, cell-type-resolved profiling, and in vivo perturbation in clinically relevant models. Collectively, the review positions IGFBP-6 as a nuanced regulator of liver pathophysiology and a promising, yet underexplored, lever for diagnosis and therapy. Full article

Oocyte-granulosa cell complexes (OGCs) cultivation is crucial for advancing reproductive biotechnology but remains incomplete and needs further optimization. Insulin-like growth factor-I (IGF-I) regulates granulosa cell proliferation and apoptosis, and numerous studies have confirmed its role in promoting ovarian follicle development. Porcine follicular fluid (PFF) contains factors beneficial for oocyte growth, which may enhance oocyte development. To investigate whether IGF-I and PFF improve the in vitro culture efficiency of porcine OGCs, we cultured OGCs with IGF-I (0, 10, 50, 100 ng/mL) and PFF (from 3 to 6 mm follicles) at concentrations of 0, 2.5%, 5%, 10%, respectively. The results revealed that 50 and 100 ng/mL IGF-I significantly increased the antrum formation rate of OGCs (from 61.11 ± 7.35% to 88.89 ± 7.35%) and diameter growth of oocytes (from 108.77 ± 0.27 µm to 114.94 ± 0.58 and 113.29 ± 0.50 µm, respectively). However, only the 50 ng/mL group, but not the 100 ng/mL group, significantly improved the maturation rate (38.13 ± 3.77% vs. 25.00 ± 3.27%, p < 0.05) of oocytes. Additionally, 50 ng/mL IGF-I downregulated BAX (a pro-apoptotic gene) and upregulated BCL-2 (an anti-apoptotic factor) in granulosa cells, ultimately reducing apoptosis. In contrast, none of the PFF doses used in this study induced the formation of enclosed antrum-like structures in OGCs, nor did they significantly enhance their in vitro development. Our findings demonstrate that 50 ng/mL IGF-I effectively promotes the in vitro growth of porcine early antral follicle-derived OGCs by reducing apoptosis, whereas tested PFF concentrations had no beneficial effects and induced abnormal granulosa cell growth. How PFF modulates the adherent and spreading growth of granulosa cells has not been fully elucidated and requires further clarification. Full article

Nuclear receptors (NRs) are ligand-activated transcription factors that mediate diverse cellular processes, including signalling, survival, proliferation, immune response and metabolism, through both genomic and non-genomic mechanisms in response to hormones and metabolic ligands. Given their central role in inter-organ, tissue, and cellular communication, NRs are critical for maintaining homeostasis and have become a major focus in biomedical research and drug discovery due to their association with numerous diseases. Among NRs, the NR4A subfamily (NR4A1/Nur77, NR4A2/Nurr1, and NR4A3/Nor1) responds to various stimuli—such as insulin, growth factors, inflammatory cytokines, and β-adrenergic signals—though their endogenous ligands remain unidentified. Their expression is tissue-dependent, particularly in energy-demanding tissues, where they modulate leukocyte function and promote an anti-inflammatory profile. Like other NRs, NR4As regulate acute and chronic inflammation by suppressing pro-inflammatory transcription factors (e.g., NF-κB) or enhancing their inhibitors, thereby polarising macrophages toward an anti-inflammatory phenotype. This review summarises current knowledge on the role of NR4A receptors in immune responses. Given their well-documented involvement in autoimmune diseases, inflammatory conditions, and cancer, elucidating their contributions to neuro–immune–endocrine crosstalk may uncover their therapeutic potential for immunopathological disorders. Full article

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an RNA-binding protein known to play critical roles in metabolism, cell proliferation, and tumorigenesis. Although its involvement in muscle development has been documented in several species, the function of goose IGF2BP2 remains largely unexplored. In this study, we cloned and characterized the full-length cDNA and genomic DNA sequences of goose IGF2BP2. The cDNA is 2957 bp in length and contains a 1662 bp open reading frame encoding a 553-amino acid protein with five conserved RNA-binding domains. The genomic sequence spans 12,183 bp and consists of 12 exons and 11 introns. A total of 60 genetic variants were identified, including a deletion of a G base at position 2299 (g.2299delG) that results in a frameshift mutation. Expression analysis revealed high levels of IGF2BP2 mRNA in the liver, heart, and muscle tissues of female geese across embryonic (E25d), growing (A70d), and laying (L270d) stages, consistent with a potential role in muscle development (p < 0.05). Functionally, overexpression of IGF2BP2 in skeletal muscle satellite cells (SMSCs) was associated with significant changes in the expression of several genes linked to muscle development and signaling pathways, including upregulation of IGF1, EGFR, FGF19, BMP6, BMP2, ACVR1C and WNT5A and downregulation of MYBPC3, NODAL, HOXD13, TNXB, and ADD2 (Padj < 0.01). Furthermore, protein–protein interaction (PPI) network analysis of these genes suggests that IGF2BP2 may coordinate key genes, contributing to its potential role in skeletal muscle development in geese. Full article

Background: The insulin-like growth factor 2 receptor (IGF-2R), also known as the cation-independent mannose 6-phosphate receptor (CI-M6PR), is emerging as a critical receptor for brain function and disease. IGF-2R, in fact, plays a key role in long-term memory, and its activation by several ligands shows beneficial effects in multiple neurodevelopmental and neurodegenerative disease models. Thus, its targeting is very promising for neuropsychiatric therapeutic interventions. IGF-2R’s main known functions are transport of lysosomal enzymes and regulation of developmental tissue growth, but in the brain, it also controls learning-dependent protein synthesis underlying long-term memory. However, little is known about this receptor in brain cells, including its cell-type-specific and subcellular expression. Methods: We conducted a comprehensive investigation to comparatively assess IGF-2R protein levels in different brain cell types across various brain regions in adult male C57BL/6J mice using dual and multiplex immunofluorescent staining with cell-type-specific markers. The IGF-2R protein distribution was also compared with Igf2r mRNA expression in publicly available single-cell RNA sequencing databases. Results: A ranking of IGF-2R levels in the soma of various cell types in the hippocampus and cortical regions revealed that the highest enrichment is, by far, in excitatory and inhibitory neurons, followed by vascular mural cells and subpopulations of oligodendrocyte lineage cells, with low to undetectable levels in astrocytes, microglia, vascular endothelial cells, and perivascular fibroblasts. High levels of IGF-2R were also found in ependymal cells, choroid plexus epithelial cells, and a subpopulation of meningeal fibroblast-like cells. IGF-2R was found in dendritic and putative axonal compartments throughout the brain, with particularly high levels in the stratum lucidum. The receptor’s protein distribution aligned with that of the mRNA in mouse brain databases. Conclusions: These results suggest that IGF-2R-mediated functions in the brain vary across different cell types and subcellular compartments, with the most active roles in specific subpopulations of neurons, mural cells, ependymal cells, meningeal cells, and cells of the oligodendrocyte lineage. This study advances our understanding of IGF-2R’s distribution in the brain, which is essential for formulating new hypotheses about its functions and therapeutic targeting. Full article