Search Results (18,459)

Orthodontic tooth movement (OTM) arises from force-induced mechanotransduction within the periodontal ligament (PDL), which coordinates osteoblast and osteoclast activity with immune responses to remodel the PDL and alveolar bone. This review integrates contemporary biological insights on OTM and assesses photobiomodulation (PBM) as an adjunctive therapy. We propose that mechanical and photonic inputs may interact and potentiate signaling through the Ca²⁺-NFAT, MAPK (ERK, p38, JNK), PI3K–Akt–mTOR, NF-kB, TGF-β/Smad, and Wnt/β-catenin pathways. Such interaction could influence processes such as cell proliferation, differentiation, specific cellular functions, apoptosis, autophagy, and communication between stromal and immune cells. This convergence establishes a solid foundation for understanding the context-dependent effects of PBM in OTM. In principle, PBM appears most effective as a phase-tuned adjunct, promoting early inflammatory recruitment of osteoclasts and subsequently facilitating late-phase remodeling through immunomodulatory and reparative mechanisms. However, inconsistent irradiation parameters, small sample sizes, trial heterogeneity, and the absence of mechanistic endpoints undermine current conclusions. Furthermore, the lack of integrated PBM–OTM models limits mechanistic understanding, as much of the available evidence is derived from non-OTM contexts. Overall, PBM remains a promising adjunct in orthodontics, with the potential to integrate mechanical and photonic signals in a phase-dependent manner, though its application is not yet standardized. Full article

Jin’er (Naematelia aurantialba), commonly known as golden ear, is a traditional edible fungus that has long been recognized for its medicinal and culinary properties in China. Recently, it has been registered as a new cosmetic ingredient, drawing significant attention across various fields, including medicine, food, and cosmetics, due to its array of nutritional and medicinal benefits. N. aurantialba is rich in bioactive compounds, such as polysaccharides, dietary fiber, polyphenols, and active peptides. Among these, N. aurantialba polysaccharides (NAPs) are the primary active components, exhibiting a range of biological properties, including antioxidant, hypoglycemic, immunomodulatory, intestinal flora modulatory, anti-tumor, and anti-inflammatory effects. This comprehensive review summarizes the latest advancements in the extraction, purification, structural characteristics, functional activity, and related functional mechanisms of NAPs, as well as their industrial applications. Additionally, it discusses the current limitations in NAPs research and explores its potential future research directions. This review aims to provide up-to-date information and valuable references for researchers and industry professionals interested in the potential application of NAPs in the fields of food, medicine, healthcare, and cosmetics. Full article

Background: Homocysteine (Hcy) plays a pivotal role in human reproduction, influencing gamete quality, embryo development, implantation, and pregnancy outcomes. It is central to folate and methionine metabolism and supports methylation-dependent epigenetic processes. Hyperhomocysteinemia (HHcy) exerts diverse biological effects and is associated with reproductive impairments in both sexes, affecting both spontaneous fertility and the outcome of assisted reproduction, including In Vitro Fertilization (IVF). Although the mechanisms of HHcy toxicity in reproduction are not fully understood, significant progress has been made in elucidating its effects. The emerging picture is complex, as Hcy and its metabolites impact biomolecules and cellular processes in a tissue- and sex-specific manner. Results: In men, HHcy compromises sperm deoxyribonucleic acid (DNA) integrity, methylation, and testicular microcirculation, reducing fertility potential. In women, HHcy disrupts follicular growth, oocyte competence, embryo quality, and endometrial receptivity, increasing the risk of implantation failure, miscarriage, and pregnancy complications. In assisted reproduction, HHcy and 5,10-methylenetetrahydrofolate reductase (MTHFR) variants may lower oocyte yield and embryo quality, although folate and B-vitamin supplementation can mitigate these effects. Conclusions: These effects largely reflect oxidative, inflammatory, vascular and epigenetic mechanisms, highlighting Hcy as a modifiable factor for improving natural fertility, optimizing IVF outcomes, and supporting healthy offspring development. Full article

Marine-derived bioactive peptides (MBPs) are emerging as promising natural agents for regulating inflammatory responses. MBPs, typically obtained through enzymatic hydrolysis of proteins from various marine organisms such as fish, mollusks, and algae, exhibit diverse biological activities, including antioxidant, immunomodulatory, and anti-inflammatory effects. The ability of MBPs to modulate key inflammatory mediators such as TNF-α, IL-6, and COX-2, primarily through pathways like NF-κB and MAPK, highlights the therapeutic potential of MBPs in managing chronic inflammatory diseases. However, most existing studies are confined to in vitro assays or animal models, with limited translation to human clinical applications. This review explores the stability, bioavailability, and metabolic rate of MBPs under physiological conditions, which remain poorly understood. In addition, a lack of standardized protocols for peptide extraction, purification, and efficacy evaluation hinders comparative analysis across studies and also different proteomics approaches for separation, purification, identification, and quantification of marine-derived peptides with therapeutic properties. The structure–function relationship of MBPs is also underexplored, limiting rational design and targeted applications in functional foods or therapeutic products. These limitations are largely due to a lack of consolidated information and integrated research efforts. To address these challenges, this review summarizes recent progress in identifying MBPs with anti-inflammatory potentials, outlines key mechanisms, and highlights current limitations. Additionally, this review also emphasizes the need to enhance mechanistic understanding, optimize delivery strategies, and advance clinical validation to fully realize the therapeutic potential of MBPs. Full article

Acute respiratory distress syndrome (ARDS) is a highly heterogeneous syndrome with a continuing high mortality rate. Despite intensive research, established therapies consist mainly of supportive measures, while pharmacological approaches have not yet shown any consistent survival benefits. In recent years, it has become clear that the great clinical and biological diversity of ARDS contributes significantly to the difficulty of demonstrating therapeutic effects. The phenotyping of ARDS has therefore become a central field of research. Different approaches—from clinical parameters and imaging to inflammatory and cardiovascular profiles and multi-omics analyses—have repeatedly identified reproducible subphenotypes that differ in prognosis and, in some cases, in response to therapies. Hypo- and hyperinflammatory subphenotypes have been described as particularly consistent. These are prognostically relevant and, in retrospective analyses, have also shown a differentiated response to glucocorticoids, statins, or fluid strategies. However, endotypes based on causal pathophysiological mechanisms are still largely theoretical. The concept of treatable traits illustrates the potential of personalized therapy but is currently based predominantly on retrospective findings. Future studies should use standardized terminology and multimodal approaches, take longitudinal data into account, and aim for prospective validation to define robust subphenotypes and causal endotypes. This could lay the foundation for true precision medicine in ARDS. Full article

Human remains detection (HRD) dogs are vital tools in forensic science and disaster response, but their training is limited by the restricted availability of human material. Synthetic odorants such as Sigma Pseudo™ formulations provide safer, standardized alternatives, yet current products reproduce only a fraction of the volatile organic compound (VOC) profile of decomposition. In particular, sulfur-containing volatiles, which are highly odor-active and consistently present in human remains, are often missing, reducing biological fidelity. Here, we integrate analytical chemistry with canine olfactory genetics and molecular biology to explain these limitations. Dogs possess one of the largest olfactory receptor (OR) repertoires among mammals, with high allelic diversity and specialized trace amine-associated receptors (TAARs) tuned to cadaveric amines. Together with olfactory binding proteins (OBPs) and ciliary signal transduction cascades, these molecular mechanisms highlight why incomplete VOC mixtures may fail to activate the full receptor network required for reliable odor imprinting. We propose the “sulfur gap hypothesis” and suggest hybrid training strategies combining improved synthetics with ethically sourced biological samples to enhance HRD dog performance. Full article

Human DNA is continuously exposed to endogenous and exogenous agents that generate over 100,000 lesions per cell each day. In addition to damage to nucleobases, deoxyribose, and phosphate groups, a particularly harmful class of lesions involves non-canonical DNA termini—structures deviating from the canonical 3′-hydroxyl and 5′-phosphate ends. These aberrant DNA ends can obstruct essential DNA transactions and, if left unrepaired, contribute to cytotoxicity and mutagenesis. Their biological significance is further highlighted by the severe pathologies linked to deficiencies in DNA end-processing enzymes, including inflammation, cancer predisposition syndromes, neurodegeneration, and aging. This review highlights recent advances in our understanding of the formation, prevalence, and repair mechanisms of several key non-canonical DNA end structures, including 3′-phosphate, 3′-phosphoglycolate, 3′-α,β-unsaturated aldehyde and its glutathione derivative, 5′-deoxyribose-5-phosphate, 2′-deoxyribonucleoside-5′-aldehyde, and 5′-adenosine monophosphate. These non-canonical DNA terminal structures arise from various sources, such as radical-induced oxidation of the 2-deoxyribose moiety and DNA repair pathways. While this review does not cover the full spectrum of non-canonical termini, the selected structures are emphasized based on quantitative data supporting their biological relevance. The review also discusses their broader implications in mitochondrial DNA maintenance and inflammatory signaling and highlights key knowledge gaps that warrant further investigation. Full article

Acute kidney injury (AKI) is a frequent clinical and pathological condition, often resulting from factors like ischemia, toxins, or infections, which cause a sudden and severe decline in renal function. This, in turn, significantly affects patients’ overall health and quality of life. The Sirtuin family (SIRTs), a group of Nicotinamide Adenine Dinucleotide (NAD+)-dependent deacetylases, is critically involved in key biological processes such as cellular metabolism, stress responses, aging, and DNA repair. Recent research has highlighted the vital role of SIRTs, such as SIRT1, SIRT3, and SIRT6, in the development and progression of AKI. These proteins help mitigate renal injury and facilitate kidney repair through mechanisms like antioxidant activity, anti-inflammatory responses, cellular repair, and energy metabolism. Additionally, the deacetylase activity of the SIRTs confers protection against AKI by modulating mitochondrial function, decreasing oxidative stress, and regulating autophagy. Although the precise mechanisms underlying the role of Sirtuins in AKI are still being explored, their potential as therapeutic targets is increasingly being recognized. This paper will discuss the mechanisms by which the SIRTs influence AKI and examine their potential in a future therapeutic strategy. Full article

Background: Cancer patients experience a high incidence of concomitant infections due to the effects of chemotherapy drugs and their suppressed immune function. Infection has become a major cause and an accelerating factor of cancer-related deaths. The combined use of anticancer drugs and antibiotics can produce adverse effects, necessitating the urgent search for dual-active drugs that are effective against both cancer and bacteria. Since tubulin has a homologous protein filamenting temperature-sensitive mutant Z (FtsZ) in bacteria, tubulin inhibitors have the potential to emerge as dual-active drugs against both cancer and bacteria. Methods: A comprehensive screening of a tubulin inhibitor library, encompassing 196 compounds, was conducted to evaluate their various activities. Results: Compounds 6, 23, 33, 56, 60, and 71 exhibited both anticancer and antibacterial activities in vitro, and 23, 33, 56, and 60 displayed varying degrees of FtsZ inhibitory activity. Particularly, compound 23 stood out as the most potent, exhibiting not only the strongest anticancer activity with IC₅₀ values of 12, 20, and 10 nM against A549, MCF-7 and Hela cells, respectively, but also the most exceptional antibacterial activity with minimum inhibitory concentration (MIC) values of 8, 8, 64, and 32 μM against Staphylococcus aureus (S. aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), respectively. Furthermore, compound 23 possessed the superior FtsZ inhibitory activity, facilitating polymerization. This was evident in the remarkably elongated cell morphology of Bacillus subtilis treated with compound 23. To gain a deeper understanding of the underlying mechanisms, molecular docking studies were conducted, revealing the interaction mode between compound 23 and both tubulin and FtsZ, further elucidating its multifaceted biological activities. Conclusions: The dual-active drugs obtained in this study provide a new solution to the problem of bacterial infection in cancer patients. The revealed FtsZ as the antibacterial target provides an important theoretical basis for further optimization of such drugs. Full article

Background/Objectives: Osteoarthritis (OA) is a prevalent age-related degenerative joint disease causing cartilage damage, leading to a debilitating lifestyle. However, there are currently no drugs on the market that promote cartilage repair, and advanced cases often require arthroplasty. Increasing evidence suggests that exosomes, the smallest extracellular vesicles (30–150 nm) secreted by all cell types, are involved in the pathological process of OA and play a crucial and complex role in its progression. This review aims to provide in-depth insights into exosome biology, isolation techniques, their role in OA pathophysiology, and their clinical therapeutic potential. Methods: We systematically reviewed studies published since 2020 on exosomes in OA, focusing on their biological properties, isolation techniques, pathological roles, and therapeutic applications. Results: Exosomes derived from synovial fluid, chondrocytes, synoviocytes, and mesenchymal stem cells regulate key processes in OA progression, including inflammation, apoptosis, extracellular matrix degradation, and regeneration. Various cell-derived exosomes show therapeutic potential for cartilage damage/OA. However, their mechanisms of action have not been fully investigated. Moreover, emerging methodologies, such as utilizing novel materials for exosome delivery, potentially facilitate the development of more effective and personalized therapeutic interventions. Conclusions: Exosomes exert dual roles in OA pathogenesis and therapy. Although challenges remain regarding their sources, dosage, delivery, and standardization, exosome-based strategies represent a promising cell-free therapeutic approach with potential applications in personalized and precision medicine. Full article

Cancer is a multifaceted disease characterized by uncontrolled cell division resulting from substantial disruptions of normal biological processes. Central to its development is cellular transformation, which involves a dynamic sequence of events including chromosomal translocations, genetic mutations, abnormal DNA methylation, post-translational protein modifications, and other genetic and epigenetic alterations. These changes compromise physiological regulatory mechanisms and contribute to accelerated tumor growth. A critical factor in this process is the dysregulation of transcription factors (TFs) which regulate gene expression and DNA transcription. Dysregulation of TFs initiates a cascade of biochemical events, such as abnormal DNA replication, that further enhance cell proliferation and increase genomic instability. This microenvironment not only sustains tumor growth but also promotes the accumulation of somatic mutations, thereby fueling tumor evolution and heterogeneity. In this study, we employed an in silico approach to identify TFs regulating 622 key genes whose mutations are implicated in carcinogenesis. Transcriptional regulatory networks were analyzed through bioinformatics methods to elucidate molecular pathways involved in cancer development. A thorough understanding of these processes may help to clarify the function of dysregulated TFs and facilitate the development of novel therapeutic approaches designed to make cancer treatments personalized and efficacious. Full article

Ginsenosides, the primary bioactive components of Panax ginseng, have demonstrated significant immunomodulatory potential. While major ginsenosides have been extensively studied, rare ginsenosides produced through deglycosylation, heating, and steaming show enhanced biological activities with improved bioavailability. This review aimed to comprehensively analyze the immunomodulatory mechanisms, structure-activity relationships (SARs), therapeutic applications, and clinical translation strategies of five emerging rare ginsenosides: F1, Rg5, Rk1, Rh1, and Rg2. We conducted a comprehensive literature review examining the production methods, immunological effects, molecular mechanisms, pharmacokinetics, safety profiles, and clinical applications of these five compounds. Analysis focused on chemical structures, immune cell modulation, signaling pathways, disease model efficacy, and bioavailability enhancement strategies. Ginsenoside F1 uniquely demonstrated immunostimulatory effects, enhancing natural killer (NK) cell cytotoxicity and macrophage phagocytosis through mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) activation. Conversely, Rg5, Rk1, Rh1, and Rg2 exhibited anti-inflammatory properties via distinct mechanisms: Rg5 through Toll-like receptor 4 (TLR4)/NF-κB inhibition, Rk1 via triple pathway modulation (NF-κB, p38 MAPK, signal transducer and activator of transcription (STAT)), Rh1 by selective p38 MAPK and STAT1 inhibition, and Rg2 through modulation of both central nervous system (neuroinflammation) and peripheral organ systems. Structure-activity analysis revealed that sugar moiety positions critically determine immunological outcomes. Crucially, advanced delivery systems including nanostructured lipid carriers, self-microemulsifying systems, and specialized liposomes have overcome the major translational barrier of poor bioavailability, achieving up to 2.6-fold improvements and enabling clinical development. Safety assessments demonstrated favorable tolerability profiles across preclinical and clinical studies. These five rare ginsenosides represent promising immunomodulatory agents with distinct therapeutic applications. F1’s unique immunostimulatory properties position it for cancer immunotherapy, while the complementary anti-inflammatory mechanisms of Rg5, Rk1, Rh1, and Rg2 offer opportunities for precision medicine in inflammatory diseases. Advanced formulation technologies and optimized production methods now enable their significant clinical translation potential, providing promising therapeutic options for immune-related disorders pending further development. Full article

The morphological traits of Vaccinium uliginosum L., including plant height, leaf area, and fruit weight, have changed significantly across an elevational gradient in the Changbai Mountains. To elucidate the molecular mechanisms underlying these morphological variations, RNA-Seq technology was employed to identify differentially expressed genes (DEGs), key metabolic pathways, and associated biological functions of V. uliginosum at seven elevations in the Changbai Mountains. A total of 1190 DEGs significantly associated with morphological variations were identified. These genes are mainly involved in lipid synthesis, carbohydrate metabolism, energy metabolism, and signal transduction. Redundancy analysis (RDA) revealed that fatty acyl-ACP thioesterase B (FATB) and ribulose-bisphosphate carboxylase small subunit (cbbS) exhibited a significant association with morphological variation. Integrated analysis indicated that high-altitude plants likely enhance lipid synthesis and cell wall stability while also inhibiting photosynthesis and carbohydrate metabolism. The regulatory mechanisms underlying hormone signal transduction may be relatively complex, as evidenced by the enhanced activity of gibberellin and reduced biological effects of auxin, abscisic acid, and ethylene. This study is the first to provide transcriptomic evidence elucidating the genetic basis of altitudinal morphological adaptation in V. uliginosum, integrating phenotypic traits with gene expression profiles across an elevational gradient. Full article

Background: Parkinson’s disease (PD) is characterized not only by motor dysfunction but also by widespread degeneration across cortico-striatal, limbic, and cortical circuits. Mounting evidence suggests that tau and α-synuclein pathology underlie these processes, though how these proteinopathies translate into affective and cognitive outcomes remains uncertain. Depression and anxiety are highly prevalent in PD, yet the biological correlates of these affective disturbances are poorly defined. Methods: This is a retrospective analysis of existing data from the Parkinson’s Progression Markers Initiative (PPMI). Montreal Cognitive Assessment (MoCA), geriatric depression scale (GDS), and State-Trait Anxiety Inventory (STAI) were used to assess cognition, depression, and anxiety in PD, respectively. The CSF biomarkers evaluated were Aβ42, t-tau, and p-tau181, using Elecsys electro-chemiluminescence immunoassays on the cobas e601 platform (Roche Diagnostics). Results: From the 4380 patients who had GDS information, the MoCA test was collected from 438 patients, and 445 from the GDS test for depression, and the STAI screening for anxiety. There were no significant differences in biomarker levels between patients with depression (GDS ≥ 5) and those without (GDS < 5), nor between patients with anxiety (STAI > 40) and those with lower anxiety scores (STAI ≤ 40). In contrast, cognitive outcomes showed clear associations. Patients with cognitive impairment (MoCA < 26) demonstrated higher levels of pTau (p = 0.02) and tTau (p = 0.01), as well as elevated pTau/Aβ42 (p = 0.003) and tTau/Aβ42 (p = 0.002) ratios compared to those with MoCA ≥ 26. In multivariate analysis, both pTau/Aβ42 > 0.022 (OR 4.64, 95% CI 1.67–13.8) and tTau/Aβ42 > 0.26 (OR 4.18, 95% CI 1.6–11.5) remained significantly associated with cognitive decline. In a longitudinal analysis in the first 3 years of follow-up, cognition in PD remained lower than in controls, while CSF p-tau and Aβ42 remained higher in controls. Conclusions: In our cohort, no associations were found between CSF biomarkers and depression or anxiety, underscoring that mood disturbances in PD are likely mediated by alternative mechanisms such as monoaminergic dysregulation, neuroinflammation, and psychosocial factors. By contrast, cognitive performance (MoCA) was clearly linked to tau-related pathology, rather than α-synuclein or Aβ42 alone. While Aβ42 and α-synuclein remain useful for staging and assessing global disease risk, our findings highlight the specificity of tau-related pathology for cognitive outcomes in PD. Full article

Dermatan sulfate (DS) is an animal glycosaminoglycan with significant structural heterogeneity and a high, but variable density of negative electric charge. Owing to these characteristics DS displays a high degree of biological reactivity that is subject to regulation. We previously demonstrated that structural variants of DS rapidly induce moderate necroptosis in luminal breast cancer cells. In the present study, we investigated the intracellular molecular mechanism(s) that may underlie this effect, focusing on the expression of key regulators of intrinsic (BCL-2A1) and extrinsic (cFLIP) apoptosis, autophagy (Beclin-1), and oxidative stress protection (heme oxygenase-1 (HO-1)). Using RT-qPCR, Western blotting, immunofluorescence, and pharmacological inhibition, we have shown for the first time that DS, depending on its structure and the cancer cell line, can rapidly, albeit transiently, upregulate either the long or short cFLIP splicing variant and also reduce the level of HO-1. These effects are mediated via DS-triggered PI3K and/or NFκB signaling. Moreover, DS can also influence the intracellular distribution of these proteins. In contrast, this glycan did not affect the expression of BCL-2A1 and BECN1. These findings indicate that DS induces coordinated molecular remodeling in luminal breast cancer cells that creates an intracellular environment favorable for necroptosis induction. Full article