Search Results (666)

Musculoskeletal pain is a major cause of disability and long-term analgesic use, increasing interest in safe non-pharmacological interventions. This focused narrative review examines light-emitting diode (LED)-based photobiomodulation (PBM) for musculoskeletal pain, integrating molecular, mechanistic, clinical, and translational evidence. Red and near-infrared LED-PBM may act through mitochondrial and non-mitochondrial photoacceptors, modulation of ATP production, reactive oxygen species, nitric oxide, calcium signaling, inflammatory pathways, oxidative stress responses, and extracellular matrix repair. Clinical evidence suggests a potential benefit in selected conditions, particularly temporomandibular disorders, fibromyalgia, cervical and myofascial pain, tendon and plantar fascia disorders, knee osteoarthritis, and mild-to-moderate peripheral nerve compression, while findings for non-specific low back pain remain inconsistent. The reviewed literature indicates that therapeutic response depends less on emitter identity alone than on wavelength, irradiance, radiant exposure, treatment geometry, target depth, timing, disease phenotype, and protocol quality. LED-based PBM appears generally well tolerated and clinically promising as an adjunct to rehabilitation, but current evidence is limited by heterogeneous devices, incomplete dosimetry, variable comparators, and short follow-up. Future studies should prioritize standardized reporting, depth-aware dosing, phenotype-based recruitment, biomarker-linked outcomes, and direct laser–LED comparisons under dosimetrically matched conditions. Full article

Oxidative stress is a major contributor to the development of age-related macular degeneration (AMD), and excessive oxidative stress can induce retinal pigment epithelium (RPE) dysfunction, apoptosis, and retinal degeneration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is a major enzymatic source of reactive oxygen species (ROS); however, its mechanistic role in sodium iodate (NaIO₃)-induced oxidative injury remains unclear. Tetrahydrocurcumin (THC), the major metabolite of curcumin, exhibits potent antioxidant and cytoprotective activities, but its protective effects against AMD-associated retinal degeneration have not been fully elucidated. In the present study, we investigated whether THC protects against NaIO₃-induced ROS-mediated apoptosis in RPE cells through regulation of NOX2 signaling. In vitro, THC significantly attenuated NaIO₃-induced cytotoxicity and prevented apoptosis by suppressing hydrogen peroxide (H₂O₂) production and intracellular ROS accumulation in ARPE-19 cells. THC also preserved mitochondrial membrane potential by inhibiting the Src/p47^phox/NOX2 signaling pathway and subsequently attenuated mitochondria-mediated apoptotic signaling. Furthermore, THC markedly reduced the expression of apoptotic proteins, including Bax, cleaved caspase-3, and cleaved PARP, concomitantly with suppression of Ras/Raf/MEK/ERK signaling. Mechanistically, treatment with the selective NOX2 inhibitor GSK2795039 significantly attenuated NaIO₃-induced ROS accumulation and mitochondrial depolarization, while co-treatment with THC further enhanced these protective effects. In vivo, THC ameliorated NaIO₃-induced retinal structural abnormalities by preserving the outer nuclear layer (ONL), reducing caspase-3 expression, and improving pupillary light responses in mice. Collectively, these findings demonstrate that THC protects against NaIO₃-induced retinal degeneration through suppressing NOX2-dependent oxidative stress and downstream Ras/Raf/MEK/ERK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for AMD and other oxidative stress-related retinal disorders. Full article

JAZ (Jasmonate ZIM-Domain) proteins are key negative regulators of the jasmonic acid (JA) signaling pathway and are involved in various plant growth, development, and stress regulation. However, the functions of the JAZ gene family in Camellia nitidissima remain poorly understood. Here, ten CnJAZ genes were identified at the genome-wide level, encoding 134–398 amino acids and unevenly distributed across eight chromosomes. All CnJAZs were predicted to localize to the nucleus. Based on phylogenetic and structural analyses, the ten CnJAZs were classified into five subfamilies, with members of the same subfamily sharing similar exon–intron structures. Collinearity analysis with Arabidopsis thaliana and Malus domestica suggests that the JAZ gene family shares a common ancestor. Promoter analysis revealed cis-acting elements responsive to light, methyl jasmonate (MeJA), and anaerobic stress. Transcriptome profiling showed that most CnJAZs exhibit tissue- and development-specific expression, particularly during flower development and organ formation. RT-qPCR confirmed that MeJA and gibberellin (GA₃) significantly induced the expression of CnJAZ, whereas ethylene (ETH) treatment up-regulated CnJAZ3 and CnJAZ5 by 80-fold after three hours. These findings highlight their important roles in growth, development, and hormonal regulation in C. nitidissima, laying a foundation for functional studies. Full article

Orofacial clefts are among the most common congenital craniofacial anomalies in the world. Immunity factors modulate response, inflammation, and healing in clefted tissue. This study aims to evaluate the levels of the pro-inflammatory biomarkers Granulysin, Resistin, FCGR1A, NF-kßp65, and CD68 to describe and understand the morphopathological basis of inflammation. The comparison was done between patient and control samples across milk and mixed dentition age groups. In total, 14 patient samples were analyzed with a total of 10 control samples to form two distinct control groups with milk dentition age and mixed dentition age. Samples were analyzed using light microscopy, and a semi-quantitative method of evaluation and comparison was used to determine the number of immunohistochemically positive structures of patient and control samples. Statistics included Spearman’s correlation and Fisher’s exact test to compare groups and detect significant differences. NF-kßp65 in the milk dentition age group (p = 0.043 for NF-kßp65 in connective tissue, p = 0.017 for NF-kßp65 in salivary glands), and FCGR1A and CD68 in the mixed dentition age group showed statistically significant differences in the expression of palatal tissues compared to the controls (p = 0.016 for FCGR1A in connective tissue, p = 0.048 for CD68 in epithelium). Spearman’s rank correlation revealed eight very strong correlations among several factors and one strong correlation between factors. The presence of many very strong and strong Spearman’s correlations among inflammatory factors in cleft-affected individuals suggests heightened signaling in these pathways. Furthermore, the difference in the inflammatory factor expression at different dentition ages suggests variation in the inflammation character with age. Full article

Protein kinases have key roles in cells as they regulate diverse signal transduction pathways. Mitogen-activated protein kinase (MAPK) signaling route modulates several processes, such as cell proliferation, cell programming, metabolic changes and stress responses. Within the group of proteins participating in this pathway, the MAPK kinase (MEK1) is a dimeric, 393-residue-long, dual-specificity protein kinase that phosphorylates both tyrosine and threonine residues. In this study, we explored the conformational changes occurring during the unfolding of MEK1, by using orthogonal biophysical techniques. Intrinsic fluorescence, extrinsic 8-anilinonapthalene-1-sulfonic acid (ANS) fluorescence, dynamic light scattering (DLS), and far-ultraviolet (UV) circular dichroism (CD) showed that the protein acquired a native-like conformation within a narrow pH range (8.0 to 9.0). Urea and guanidinium hydrochloride (GdmCl) denaturations followed by intrinsic and ANS fluorescence and far-UV CD, at pH 8.1, where the protein acquired a native-like conformation, showed that: (i) the apparent conformational stability of isolated MEK1 was low; and (ii) the unfolding occurred through the presence of intermediates. The presence of several unfolding intermediates was also evidenced through: (i) differential scanning calorimetry (DSC) in the absence of the ligand ATP; and (ii) unfolding simulations with the help of computational techniques based on constraint network analysis (CNA). We propose that the apparent low stability of this protein was related to its flexibility and modulates its ability to interact with diverse molecular partners. Full article

The FAR-RED IMPAIRED RESPONSE 1 (FAR1) and FAR-RED ELONGATED HYPOCOTYL 3 (FHY3) transcription factors, together with other members of the FAR1-RELATED SEQUENCE (FRS) and FRS-RELATED FACTOR (FRF) families, represent a striking example of transposable element domestication in plants. Derived from ancient Mutator-like element (MULE) transposases, these proteins have been repurposed as transcriptional regulators throughout the plant kingdom. FHY3 and FAR1 were first identified in Arabidopsis thaliana as positive regulators of phytochrome A (phyA) signaling. They participate in the coordination of light signaling with the circadian clock, chlorophyll biosynthesis, hormone pathways, stress responses, flowering time, shoot branching, leaf senescence, seed dormancy, and phosphate homeostasis. At the molecular level, FHY3 and FAR1 regulate gene expression mainly by binding to the conserved FHY3/FAR1-binding site, FBS, with the sequence CACGCGC, in the promoters of target genes. They also act through protein interactions with key signaling regulators, including HY5, PIFs, EIN3, TOC1, and SPL transcription factors. In this review, we summarize the molecular basis of FHY3/FAR1 gene family function, discuss the roles and mutant phenotypes of characterized family members, and highlight recent advances from other plant species beyond Arabidopsis. Collectively, this gene family illustrates how domesticated transposase-derived proteins have evolved into key regulators of plant development and environmental adaptation. Full article

Salinity stress progressively restricts rapeseed (Brassica napus L.) growth and productivity. However, the molecular mechanism underlying its tolerance remains poorly understood. This study aims to shed light on differential responses between shoots and roots, and further clarify the regulatory mechanisms of ion homeostasis and oxidative defense under early-and long-term salt stress. Under salt stress, the Na⁺/K⁺ ratio increased by 46.26% and 26.33% in shoots and roots, respectively. Activities of SOD and POD increased in both tissues, while CAT activity declined in shoots. MDA content was significantly higher in roots. Transcriptome PCA clearly separated samples of early-term (3–48 h for shoots, 3–24 h for roots) from long-term (72 h 25 d for shoots, 48 h 25 d for roots) salt stress. SOD2 and UGT72E1 were significantly up-regulated in shoots but down-regulated in roots. CAT2 exhibited strongly up-regulation in roots than shoots, whereas RBOHC was markedly down-regulated in roots relative to shoots. Additionally, CAT1 was mainly up-regulated at the early-term salt stress. Most DEGs involved in phenylpropanoid biosynthesis (CYP73A5, PAL2, CCR1/2, CAD1/5, COMT1 and PER66) were up-regulated in both tissues. Notably, HCT and CSE exhibited a striking tissue-specific antioxidant pattern, down-regulated in shoots but up-regulated in roots. PER34 was specifically induced at early-term, and PER31/63/169 were exclusively activated under long-term salt stress in roots. Moreover, we performed weighted gene co-expression network analysis (WGCNA) to describe tissue- and time-specific transcriptional dynamics that occur in rapeseed under salt stress. Several hub genes, including ABI5, MPK6, CAD5, NADK1 and LFG2, exhibited high correlations with early-term salt stress responses in roots. These genes are mainly enriched in transcription factors and hormone signaling pathways, and function in antioxidant defense and redox homeostasis. This study suggests distinct spatiotemporal salt stress response patterns in rapeseed and identifies key genes for salt-tolerance breeding. Full article

Objective: Rapid vertical manoeuvres and intermittent vibration in autonomous electric vertical take-off and landing (eVTOL) aircraft can provoke pronounced psychological anxiety in passengers. To address this, we propose a closed-loop adaptive system that integrates an in-ear wearable sensor with dynamic regulation of the cabin microenvironment, enabling real-time monitoring of each passenger’s autonomic state and delivering individualised mitigation through a continuous sense–analyse–intervene–feedback loop. Methods: The system is built around a pair of custom in-ear modules that integrate dual-wavelength photoplethysmography (PPG; 525 nm green and 940 nm infrared), galvanic skin response (GSR), and a six-axis inertial measurement unit (IMU) sampled at 200 Hz. To suppress the 20–80 Hz vibration generated by the distributed electric propulsion system, a compliant silicone damping sleeve attenuates high-frequency components at the hardware level, while a Kalman filter fuses the IMU and PPG streams and an adaptive notch filter removes residual rotor harmonics. The pipeline raises the heart-rate-variability (HRV) signal-to-noise ratio (SNR) to 24.1 dB, with a Pearson correlation of 0.96 against a medical-grade chest strap. A hybrid CNN–LSTM network—two convolutional layers (32 filters each) followed by two LSTM layers (128 hidden units)—predicts impending anxiety from HRV time-domain features (RMSSD, pNN50) and frequency-domain features (LF/HF ratio), triggering intervention 8.2 s in advance on average. According to the predicted anxiety level (mild/moderate/severe), a fuzzy controller modulates transcutaneous auricular vagus nerve stimulation (1–5 mA), the binaural-beat frequency (4–8 Hz, theta band), and the cabin lighting colour temperature (2700–6500 K) in real time. The intervention parameters are continuously refined by SPSA-based stochastic optimisation of the HRV recovery rate (step size 0.01; updated every 30 s). Results: In a randomised controlled experiment conducted in a simulated flight environment (N = 50; aged 22–45 years; 1:1 sex ratio), the active group reached physiological recovery in 52.3 s on average, compared with 98.6 s for the sham-controlled group—a 47% reduction (Cohen’s d = 1.24, p < 0.001). User acceptance reached 94%. Conclusions: The proposed in-ear platform enables closed-loop adaptive regulation of anxiety in the eVTOL cabin and overcomes the limitations of conventional passive mitigation strategies. By combining vibration-tolerant physiological sensing with multimodal environmental control, the work offers a practical pathway for improving passenger experience in urban air mobility and provides a useful reference for human-factors standards governing autonomous aircraft. Full article

Acute kidney injury (AKI) is a life-threatening event prevalent in hospitalized patients but also not rare among endurance sports athletes. Hypoxia, oxidative stress, and sterile inflammation are the key pathophysiological factors driving kidney damage in AKI. Zinc is an essential trace element required for the intact function of approximately 3000 proteins (~10% of the human proteome), including over 300 enzymes for which zinc serves as a cofactor. Cell biological tasks of zinc signaling include adaptive responses to hypoxia and oxidative stress, as well as anti-inflammatory effects. The underlying molecular pathways involve modulation of hypoxia-inducible factor signaling, suppression of reactive oxygen species (ROS) generation, and inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), the latter being the major pro-inflammatory transcription factor. As a catalytic cofactor for the “classical” histone deacetylases, zinc is essential for epigenetic control of gene expression, thereby exerting further adaptive effects. Apart from the intracellular zinc signaling, extracellular zinc elicits cytoprotective and anti-inflammatory effects via the G Protein-Coupled Receptor 39 (GPR39). GPR39 activation by zinc binding may exert antioxidant and anti-inflammatory effects mediated by the zinc-finger protein A20 (TNFAIP3) and NF-κB suppression, followed by reduced production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), and IL-6. At the same time, GPR39 signaling may stimulates the release of the anti-inflammatory cytokine IL-10, thus shifting the kidney tissue towards an anti-inflammatory milieu, promoting renal recovery. The present review focuses on the role of zinc in AKI to identify potential therapeutic strategies targeting zinc signaling for renoprotection and biomarker-based risk stratification. Full article

Grapevine (Vitis vinifera L.) is a key fruit crop affected by abiotic stresses such as salinity, drought, and temperature extremes. The Regulator of Chromosome Condensation 1 (RCC1) family, involved in regulating Ran GTPase activation, nucleocytoplasmic transport, and chromatin organization, has not been comprehensively characterized in grapevine. In this study, we identified 26 VvRCC1 genes, which were classified into five phylogenetic groups, and analyzed their distribution across the grapevine genome. These genes exhibited significant diversity in physicochemical properties, suggesting functional divergence. Expression profiling revealed distinct spatiotemporal patterns, indicating roles in both vegetative growth and reproductive development. Notably, several VvRCC1 genes showed differential responses to salinity, drought, and heat stress. Importantly, VvRCC1-17, identified as UVR8, was shown to regulate anthocyanin biosynthesis under UV-B exposure. OE-VvUVR8 transgenic grape calli exhibited increased anthocyanin accumulation, reflected in a distinct red coloration compared to wild-type calli. This finding links UVR8 to light signaling and pigmentation pathways in grapevine, providing the first comprehensive analysis of the RCC1 gene family in grapevine and highlighting VvRCC1-17 (UVR8) as a key regulator of UV-induced anthocyanin biosynthesis, offering insights into the molecular mechanisms of stress adaptation and pigment regulation. Full article

Nuclear factor-κB (NF-κB) is a critical regulator of inflammation and stress response signaling in acute kidney injury (AKI). Increasing evidence demonstrates that NF-κB signaling is directly related to oxidative stress, autophagy, mitochondrial malfunction, and apoptosis in the process of AKI. Injury-related stimuli, including ischemia–reperfusion, sepsis, nephrotoxins, reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), activate canonical and non-canonical NF-κB pathways, resulting in renal inflammation and tubular injury. Recent investigations have shown that TLR4/NF-κB signaling, NLRP3 inflammasome activation, defective autophagy, and mitochondrial dysfunction mediate inflammatory and pro-apoptotic responses in AKI. On the other hand, autophagy-associated proteins such as microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin-1 may play renoprotective roles through the regulation of NF-κB signaling. This review tries to cover the knowledge regarding NF-κB signaling in AKI and to emphasize the possible function of NF-κB signaling in the control of inflammation, autophagy, and apoptosis. It also seeks to provide some insight into future research directions that may guide the development of more effective therapies for AKI. Full article

Phytochrome-interacting factors (PIFs) were initially recognized as pivotal regulators of plant light signaling pathways. However, mounting evidence suggests that PIFs also exert significant influences on plant development and responses to stress. Here, we identified seven PIF genes in the potato genome and conducted comprehensive characterizations through phylogenetics, gene structure, conserved motif, synteny, chromosomal location analyses and cis-regulatory element. Transcriptome data and gene expression analysis showed that the StPIF4 gene was markedly induced by mannitol-induced water deficit. Additionally, the StPIF4 protein was primarily localized in the nucleus and plasma membrane. In order to explore the function of the StPIF4 gene under mannitol-induced water deficit, the StPIF4 gene was cloned, and several StPIF4 overexpression (OE) lines (OE-8, OE-10, and OE-11) and three RNA interference (RNAi) transgenic lines (RNAi-5, RNAi-9, and RNAi-11) were obtained. The OE lines displayed notable enhancements in various growth parameters such as plant height, leaf number, branch number, fresh weight, dry weight, total root length, root surface area, number of root forks, and number of root tips under mannitol-induced water deficit compared to the wild-type (WT) lines, whereas these parameters were significantly decreased in the RNAi lines. The activities of antioxidant enzymes (SOD, POD, CAT) and the accumulation of proline and soluble sugars were also significantly increased under mannitol-induced water deficit, whereas the levels of thiobarbituric acid reactive substances (TBARSs) and reactive oxygen species (ROS), including hydrogen peroxide (H₂O₂) and O₂⁻, were significantly reduced in the OE lines compared to WT plants under mannitol-induced water deficit. Moreover, the stomatal aperture of the leaves and the water loss rate in the leaves of the OE lines were significantly reduced under mannitol-induced water deficit compared to the WT plants, whereas for the RNAi lines they were significantly increased. In addition, the overexpression of StPIF4 also upregulated expression of drought-responsive genes and ABA content under mannitol-induced water deficit. Collectively, these results highlight the positive role of the StPIF4 gene in enhancing potato tolerance to mannitol-induced water deficit by decreasing stomatal aperture, enhancing ROS scavenging and mitigating oxidative damage. Full article

Gestational diabetes mellitus (GDM) is increasingly recognized as a complex pathology rooted in systemic and organelle-level dysfunction, specifically involving chronic low-grade inflammation (CLGI), mitochondrial impairment, and endoplasmic reticulum (ER) stress. Central to this pathophysiology is mitochondrial dysfunction, characterized by reduced respiration, impaired metabolic flexibility, and dysregulated fission/fusion machinery, which fuels a self-perpetuating cycle of reactive oxygen species (ROS) production. Concurrently, chronic ER stress triggered by hyperglycemia and lipotoxicity activates the unfolded protein response (UPR), further amplifying redox imbalance through the Endoplasmic Reticulum Oxidoreductin 1/Protein Disulfide Isomerase (ERO1/PDI) axis and bridging metabolic toxicity to inflammation via c-Jun N-terminal kinase (JNK) and nuclear factor kappa-light-chain–enhancer of activated B cells (NF-κB) signaling. The Advanced Glycation Endproducts (AGEs) and the Receptor for Advanced Glycation Endproducts (RAGE) axis act as a molecular catalyst that sequester antioxidants and drive pro-inflammatory feedback loops. These converging mechanisms culminate in profound placental maladaptation, including structural abnormalities like chorangiosis and functional defects in nutrient transport mediated by hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. This review article provides insight into recent evidence to elucidate the meta-inflammatory environment of GDM, where modest but sustained elevations in biomarkers like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) disrupt redox homeostasis and impair insulin signaling pathways through the activation of stress-sensitive kinases. By integrating these molecular perspectives, the article underscores the necessity of targeting the systemic inflammatory and oxidative continuum spanning pre-conception to the antenatal period through lifestyle interventions and emerging therapeutic strategies to mitigate GDM risk and improve maternal–fetal outcomes. Full article

Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD), which is marked by severe abdominal pain, weight loss, perianal bleeding, and diarrhea. This study successfully isolated and purified four low-molecular-weight fucoidan oligosaccharides through acid hydrolysis and Bio Gel P10 gel filtration. The molecular weights were 2.9 × 10⁴–1.36 × 10⁵ Da, 182–1012 Da, 161–939 Da and 161–939 Da, respectively. A mouse model of colitis was induced using Dextran Sulfate Sodium (DSS). The results indicated that fucoidan and fucoidan oligosaccharides could ameliorate murine ulcerative colitis, with the oligosaccharides (200 mg/kg/d) demonstrating superior therapeutic effects. This superiority was likely attributed to the lower molecular weight and higher content of total sugars and fucose. The primary mechanisms involved the modulation of gene and protein expression levels associated with the Toll-like receptor 4, Myeloid differentiation primary response 88, nuclear factor kappa-light-chain-enhancer of activated B cells, p65, and Inhibitor of kappa light polypeptide gene enhancer in B cells, alpha (TLR4, MYD88, NF-κB p65, and IκB-α) signaling pathways, which reduce the production of inflammatory cytokines such as tumor necrosis factor-alpha, Interleukin-1 beta and Interleukin-6 (TNF-α, IL-1β, and IL-6). Additionally, these oligosaccharides alleviated oxidative stress, enhanced the levels of intestinal barrier proteins (Claudin family member 4 and Zonula occludens protein 1), regulated the abundance and diversity of the gut microbiota, and increased the levels of short-chain fatty acids (SCFAs) in the intestine. It is worth emphasizing that this study can only demonstrate that fucoidan oligosaccharides have a mitigating effect on intestinal inflammation in mice. Further research is needed in the future to investigate the structure–activity relationship of fucoidan oligosaccharides and their impact on human intestinal microbiota, in order to further elucidate their anti-inflammatory mechanisms. Full article

α-Crystallin, the predominant protein of the eye lens, possesses molecular chaperone activity and antioxidative properties, both of which are essential for maintaining lens transparency. Its chaperone function prevents the formation of light-scattering protein aggregates, while its antioxidative activity mitigates oxidative stress through both direct and indirect mechanisms. However, with aging, α-crystallin undergoes cumulative post-translational modifications and oxidative damage, leading to protein crosslinking and a decline in chaperone efficacy. Notably, α-crystallin exhibits free radical-scavenging activity comparable to that of serum albumin, a well-characterized antioxidant protein. In addition, its ability to bind redox-active metal ions and convert them into redox-inactive forms significantly reduces reactive oxygen species (ROS) generation in vivo. α-Crystallin also interacts with key proteins and signaling pathways involved in oxidative stress responses, further enhancing its multifunctional protective role. This review summarizes current evidence on the antioxidative properties of α-crystallin and their relationship to its chaperone function, highlighting its importance in lens homeostasis and age-related cataract formation. Full article