Search Results (10,122)

Background: Doxorubicin (Dox)-induced cardiotoxicity is the most important side effect of the drug and significantly limits its use in susceptible patients. Therefore, preventive measures are required to alleviate the Dox-induced cardiac failure. In this study, curcumin, a strong antioxidant agent, was investigated for its potential protective effect on dox-induced cardiotoxicity with its effect on Apelin expression as a mediator of cardiac function. Methods: Wistar albino rats were equally divided into four groups as Control, DOX, CUR, and CUR+DOX. Dox was administered a single dose of 20 mg/kg bw intraperitoneally while 100 mg/kg bw curcumin was given orally for 14 days before the Dox use. Results: DOX group showed a prolonged QT interval on an electrocardiogram and elevated cardiac troponin levels. In biochemical analyses, decreased Superoxide Dismutase activity and increased Malondialdehyde level and Catalase activity were detected in DOX group. Gene expression of Apelin decreased significantly while NF-κB increased in DOX group. Degenerative changes in histopathology, and increased iNOS and nitrotyrosine immunoreactivity were detected in DOX group. However, no significant changes were observed at reduced Glutathione, TNF-, and IL-1β levels. Curcumin use in Dox-given rats altered most of the disturbed parameters investigated in this study, indicating an alleviating effect on Dox-induced cardiotoxicity. Serum and heart Apelin levels and mRNA expression in heart tissue were detected to significantly increase in CUR+DOX group as compared to DOX group. Furthermore, NF-κB mRNA expression was significantly decreased in heart tissue of CUR+DOX group compared with the DOX group. Conclusions: The results suggest that Apelin acts as an important mediator in Dox cardiotoxicity and may be used as a target for treatment of certain cardiomyopathies. By regulating Apelin expression, curcumin may serve as a potential adjunct in cardioprotective approaches. Full article

Chronic stress (CS) is known to induce testicular oxidative stress and apoptosis. Fruit of Momordica charantia (FMC) has antioxidant capacity to protect tissue damage, but its effect on sexual activity and testicular damage caused by CS has never been documented. This study aimed to investigate the impact of FMC extract against testicular damage and sexual dysfunction in chronic unpredictable stress (CUS) rats. Rats were divided into four groups and pretreated with vehicle or FMC (40 and 80 mg/kg) before CUS induction for 56 days. Sexual behaviors, serum hormones, and sperm quality were analyzed. Testes were collected to determine daily sperm production (DSP), malondialdehyde (MDA) level, and expressions of cleaved apoptotic proteins. Testicular DNA fragmentation, as revealed by TUNEL and morphometric analysis, was observed. FMC improved sexual activity, increased testosterone levels, and sperm count with improvements in DSP, testicular morphometrics, and MDA levels. Moreover, TUNEL-positive cells and expression of caspase 3 in the testis were decreased in FMC rats. FMC has antioxidant potential and could protect against male sexual dysfunction and testicular damage caused by stress-related apoptosis. It is a potential extract to be developed as a supplement in preventing CS-male subfertility. However, future studies about the optimal dose and clinical trials are required. Full article

Pubertal molting represents a pivotal transition in the life cycle of crustaceans, marking the shift from somatic growth to reproductive development. In mud crabs, mating is known to facilitate this process, yet the molecular mechanisms remain poorly understood. Here, we applied full-length transcriptome sequencing to characterize changes in gene expression and alternative splicing (AS) across post-mating ovarian development. AS analysis revealed extensive transcript diversity, predominantly alternative first exon (AF) and alternative 5′ splice site (A5) events, enriched in genes linked to chromatin remodeling, protein regulation, and metabolism, underscoring AS as a fine-tuning mechanism in ovarian development. Comparative analyses revealed profound molecular reprogramming after mating. In the UM vs. M1 comparison, pathways related to serotonin and catecholamine signaling were enriched, suggesting early neuroendocrine regulation. Serotonin likely promoted, while dopamine inhibited, oocyte maturation, indicating a potential “inhibition–activation” switch. In the UM vs. M3 comparison, pathways associated with oxidative phosphorylation, ATP biosynthesis, and lipid metabolism were upregulated, reflecting heightened energy demands during vitellogenesis. ECM-receptor interaction, HIF-1, and IL-17 signaling pathways further pointed to structural remodeling and tissue regulation. Enhanced antioxidant defenses, including upregulation of SOD2, CAT, GPX4, and GSTO1, highlighted the importance of redox homeostasis. Together, these findings provide the first comprehensive view of transcriptional and splicing dynamics underlying post-mating ovarian maturation in Scylla paramamosain, offering novel insights into the molecular basis of crustacean reproduction. Full article

Background: Ultraviolet B (UVB) radiation accelerates skin aging by inducing oxidative stress, collagen degradation, and cellular senescence. Although Petasites japonicus is known for its antioxidant properties, its anti-photoaging potential remains underexplored. This research explored the protective properties of a hot water extract from P. japonicus leaves (KP-1) against photoaging caused by UVB exposure. Methods: Hairless mice were exposed to UVB three times per week and orally administered KP-1 for 13 weeks. Wrinkle formation, epidermal thickness, skin hydration, and collagen content were assessed. Protein expression related to MAPK/AP-1, TGF-β/Smad2/3, and p53/p21 pathways was analyzed by Western blotting. Results: KP-1 significantly reduced UVB-induced wrinkle area, epidermal and dermal thickening, and transepidermal water loss while restoring collagen density and skin hydration. KP-1 inhibited MMP-1 expression, enhanced COL1A1 levels, suppressed MAPK/AP-1 activation, and activated TGF-β/Smad2/3 signaling. It also balanced p53/p21 expression and restored cyclin D1 and CDK4 levels, thereby preventing UVB-induced senescence. Conclusions: The findings of this research revealed that KP-1 can serve as a promising natural substance for safeguarding the skin from damage and aging caused by UVB exposure. Full article

Leprosy is a chronic infectious disease that targets the peripheral nervous system, leading to peripheral neuropathy. Mycobacterium leprae primarily infects Schwann cells, adipocytes, and macrophages, altering their metabolism and gene expression. This study investigates the metabolic interaction between M. leprae and Schwann cells, with a focus on indoleamine 2,3-dioxygenase (IDO), a key enzyme in tryptophan catabolism via the kynurenine pathway. We found that M. leprae induces IDO expression in Schwann cells, suggesting a role in immune modulation and neuropathy. Inhibition of IDO with 1-methyl-L-tryptophan (1-MT) reduced Schwann cell viability and metabolic activity in response to M. leprae. After 24 h of infection, M. leprae impaired mitochondrial membrane potential, although no significant changes in autophagy or mitochondrial ultrastructure were observed by electron microscopy. Interestingly, IDO1 inhibition upregulated the expression of antioxidant genes, including GPX4, NFE2L2, and HMOX1. In conclusion, these findings highlight a central role for IDO in shaping the metabolic and immunological response of Schwann cells to M. leprae infection. IDO induction contributes to immune regulation and cellular stress, while its inhibition disrupts cell viability and promotes antioxidant gene expression. These results position IDO as a potential therapeutic target for modulating host–pathogen interactions and mitigating nerve damage in leprosy. Full article

Dendrobium officinale (Orchidaceae) is a commonly used medicinal and edible herb. Although its anti-ageing properties have been demonstrated, the underlying mechanisms remain unclear. We employed network pharmacology and molecular biology techniques to systematically explore its anti-ageing mechanisms. An ageing model was established using D-galactose-induced Kunming mice. D. officinale significantly ameliorated ageing-related symptoms, including behavioural impairment and organ index reduction. It enhanced antioxidant capacity by increasing serum T-AOC levels and restoring renal activities of key antioxidant enzymes (SOD, GSH-Px, CAT) while reducing MDA; it suppressed serum TNF-α levels, indicating anti-inflammatory effects. Histopathological examination revealed that D. officinale alleviated D-galactose-induced renal damage, including tubular cell swelling and glomerular capsule widening. Network pharmacology identified 8 core active compounds (e.g., 5,7-dihydroxyflavone, naringenin) and 10 key targets (e.g., HSP90AA1, EGFR, MAPK3). KEGG analysis highlighted pathways including neuroactive ligand–receptor interaction, cAMP signalling, and calcium signalling. Molecular docking confirmed strong binding affinities between core compounds and key targets. Western blotting and immunohistochemistry validated that D. officinale upregulated EGFR, HSP90AA1, ERK, and GAPDH expression in renal tissues. In summary, D. officinale exerts anti-ageing effects by modulating oxidative stress, suppressing inflammation, and regulating multiple signalling pathways. Our findings provide a scientific rationale for its application in anti-ageing interventions. Full article

Background: Parkinson’s disease (PD) is a neurodegenerative disorder for which no curative therapies currently exist. Experimental models employing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduce PD features such as striatal dopaminergic dysfunction and motor deficits. Various MPTP dosing regimens are used to screen drug candidates for PD, but their validity is limited because of the predominant use of young male animals. Sex bias is another issue that is underrepresented in PD research, since females are more susceptible to this pathology. Here, we studied the model of bolus administration of MPTP (30 mg/kg) in aged female mice and assessed its sensitivity to the antioxidants fullerene C₆₀ and fullerenol C₆₀(OH)₂₄, given that oxidative stress is a key contributor to PD. Methods: 12-month-old female C57BL/6 mice received fullerene (0.1 mg/kg/day, via diet) or fullerenol (0.15 mg/kg/day, via drinking water). On day 10, mice were injected with MPTP. We studied tremor, piloerection, and behavior in the pole test, rotarod, pole test, and open field. High-performance liquid chromatography (HPLC) was employed to study dopaminergic neurotransmission, and the expression levels of its molecular regulators and nitric oxide synthase (NOS)-related targets were investigated using RT-PCR in the striatum and cortex. Results: MPTP-challenged mice displayed profound impairment in markers of dopaminergic neurotransmission and cellular distress, and showed disrupted motor behavior and vegetative functions. Antioxidant-treated animals that received a bolus injection of MPTP demonstrated partial preservation of tremor response, dopaminergic parameters, and iNOS and nNOS gene expression, although motor performance in the pole test was only modestly improved. Fullerenol appeared more effective in decreasing MPTP-induced neurochemical changes. Conclusions: The applied MPTP model showed its validity in mimicking PD features and was sensitive to low doses of antioxidants, suggesting its usefulness for screening drugs that target oxidative and nitrosative stress. The neuroprotective effects of fullerene-based compounds suggest their potential utility in the treatment of PD. Full article

A limited supply and price shortages of fishmeal with the expansion of aquaculture make it necessary to seek alternative protein sources. Soybean meal (SM) has been the widely preferred replacer for fishmeal in fish diets. Nevertheless, this substitution, especially when given at high doses, potentially shows adverse impact on fish intestinal health. This study aimed to investigate the effect of replacing fishmeal with SM on intestinal health in olive flounder (Paralichthys olivaceus). A 56-day feeding trial was conducted with 450 juvenile fish (initial weight: 6.32 ± 0.01 g) randomly allocated to five diets with graded SM replacement: 0% (FM), 12% (SM12), 24% (SM24), 36% (SM36), and 48% (SM48). The results demonstrated that concentrations of glucose, total triglyceride, and low-density lipoprotein cholesterol increased, whereas total protein and high-density lipoprotein cholesterol contents, and lysozyme activity decreased in serum with increasing dietary SM levels. Meanwhile, total antioxidant capacity and superoxide dismutase activity significantly decreased at replacement levels exceeding 24%, accompanied by elevated malondialdehyde concentration (p < 0.05). Compared with the FM group, the SM24, SM36, and SM48 groups showed significantly reduced VH and increased lamina propria width (p < 0.05). Increasing dietary SM levels upregulated expression of genes related to endoplasmic reticulum stress (ERS) (chop, perk, and grp78), inflammation (tnf-α and il-6), and apoptosis (bax, casp3, casp6, and casp9), while downregulated anti-inflammatory cytokines (il-10 and tgf-β1) and tight junction-related genes (zo-1, zo-2, claudin-5, ocln, muc-13, and muc-15) in the intestine (p < 0.05). There were significant differences in the abundances of intestinal microbiota at both the phylum and genus levels among the FM, SM24, and SM36 groups (p < 0.05), but the clusters and microbiota composition of the SM24 group were more similar to those of the FM group. In conclusion, replacing 24% of fishmeal with SM induced intestinal dysfunction through evoking ERS, inflammation, barrier disruption, and microbial dysbiosis in olive flounder. Full article

High temperature stress is a critical factor affecting the growth and yield of melons (Cucumis melo L.), and improving heat tolerance is therefore crucial for stable production. While the overexpression of the CmDUF239-1 gene is known to improve salt tolerance in melons, its impact on heat tolerance remains unexplored. The role of the CmDUF239-1 gene in enhancing heat tolerance and its underlying mechanisms was investigated in this study. Melon seedlings overexpressing CmDUF239-1 (OEDUF239-1), generated via root transformation, exhibited significantly lower reductions in fresh and dry mass under heat stress compared to controls, indicating enhanced heat tolerance. One day post-stress, antioxidant enzyme activities (SOD, POD, CAT, APX, and GR) increased significantly in OEDUF239-1, while malondialdehyde (MDA) levels decreased. Additionally, proline content and the activity of its synthesizing enzyme (P5CS) rose, whereas the activity of proline dehydrogenase (ProDH) dropped. Transcriptomic and qPCR analyses revealed that CmDUF239-1 overexpression upregulated antioxidant enzyme-related genes (e.g., CmCSD1, CmPOD1) and proline-related genes (e.g., CmP5CS), as well as Heat Shock Protein (HSP) genes (e.g., CmHSP17.6II, CmHSP18.2). In summary, the enhancement of heat tolerance in melon by the CmDUF239-1 gene was mediated through the upregulation of genes involved in antioxidant defense and proline metabolism, together with increased accumulation of HSPs, providing a mechanistic basis for heat-resilient breeding programs. Full article

Background: Skin diseases of inflammatory origin, such as atopic dermatitis, psoriasis and acne, have a substantial prevalence in the world population. Natural products are particularly important at a topical level. Essential oils are examples of natural products and thyme in particular has been used for medicinal purposes due to its biological properties. Objectives: The aim of present work was to study the anti-inflammatory potential of Thymus mastichina essential oil, focusing on purified terpene-rich fractions. whose major compounds were thymol and linalool, eucalyptol and α-terpineol, and γ-terpinene and terpinolene, respectively. Additionally, a phytocannabinoid formulation containing cannabidiol (CBD) and cannabigerol (CBG) was evaluated to explore potential synergistic effects. Methods: Thymus mastichina essential oil was extracted and purified to obtain terpene-enriched fractions, which were used to develop three distinct formulations. These were screened for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and assessed for cytotoxicity in HaCaT human keratinocytes. Anti-inflammatory potential was evaluated via gene expression. Selected thyme formulations—alone or in combination with CBD/CBG—were also tested in vivo using a mouse model of acute skin inflammation. Results: The antioxidant activity of the three formulations showed a reduction in DPPH radicals. In addition, the formulations demonstrated to be safe in vitro in the human keratinocyte cell model HaCaT. Under PMA-induced inflammatory stress, the fractions modulated-inflammatory gene expression to varying degrees While terpene fractions alone showed moderate activity, their combination with CBD/CBG enhanced the anti-inflammatory response. In vivo, the gel formulations reduced oedema in a mouse model of acute inflammation. Conclusions: The data support the safe and effective use of Thymus mastichina-derived terpene fractions for topical anti-inflammatory applications. The synergistic effect observed with CBD and CBG suggests that combining essential oil terpenes with phytocannabinoids may offer a novel therapeutic strategy for managing inflammatory skin disorders. Full article

Eukaryotic cells respond to oxidative stress (OS), a physiological condition characterized by the accumulation of reactive oxygen species (ROS), through various protective mechanisms. The antioxidant defense system (ADS) is activated either by post-translational modifications of pre-existing proteins or through the induction of gene expression. These mechanisms protect cellular biomolecules against ROS damage. Although extensive research has been conducted in different species, there is limited information regarding the specific response of Yarrowia lipolytica to OS. This study aims to elucidate the molecular mechanisms by which Y. lipolytica responds to OS by analyzing the expression of genes encoding enzymes involved in antioxidant response, such as superoxide dismutase (Sod), catalase (Cat), and glutathione peroxidase (Gpx). The Y. lipolytica genome contains three CAT genes, one SOD gene, one copper chaperone for Sod (CCS) gene, and one GPX gene. The expression profiles of these genes were assessed in Y. lipolytica cells exposed to H₂O₂ [5 mM] over time. All genes reached their maximal expression within the first 15 min of exposure. Comparative analysis between young and aged Y. lipolytica cells subjected to OS revealed that young cells exhibited higher expression levels for all genes, with CAT3 and SOD showing the highest expression values. These findings suggest that the enzymes encoded by these genes play a crucial role in the antioxidant response of this species. To our knowledge, this is the first study demonstrating that the ADS in Y. lipolytica is regulated at the transcriptional level. Full article

Background: The limited self-repair capacity of nerve tissue requires a new therapeutic approach. Mesenchymal stem cells from the uterine cervix, hUCESC, have shown anti-inflammatory, regenerative, and anti-oxidative stress effects through their secretome, which makes them candidates to evaluate their potential in the context of neuronal damage. In this study, we aimed to determine whether secretome or conditioned medium of hUCESC (hUCESC-CM) has beneficial action in the treatment of PC-12 and HMC3 cells in vitro under conditions of oxidative stress and inflammation. Methods: Differentiated PC-12 cells and HMC3 cells were subjected to oxidative stress and inflammatory conditions in the presence of hUCESC-CM. The expression of factors related to both processes was evaluated by q-RT-PCR. Results: PC-12 cells treated with hUCESC-CM showed a significant increase in the expression of anti-oxidative stress factors (HO-1 and Nrf2) and a significant decrease in the expression of pro-inflammatory factors (IL1β, IL6 and TNFα). In addition, the treatment of HMC3 cells with hUCESC-CM significantly decreased the expression of IL6 and TNFα and enhanced the expression of neuroprotective factors such as BDNF and GDNF. Conclusions: Considering that both oxidative stress and inflammation are interrelated and implicated in several nerve injuries and neurodegenerative disorders, the effects of hUCESC-CM on neuronal cells are very promising. Full article

Egg yolk IgY antibody has significant application potential in aquaculture as a form of passive immunotherapy against various bacterial infections owing to its capacity for large-scale and cost-effective production. In this research, laying hens were immunized with live or inactivated Aeromonas hydrophila to produce IgY antibodies. Following this, experiments were carried out to assess the passive immune protection rates of the two types of IgY antibodies when used to immunize goldfish (Carassius auratus), which were then infected with A. hydrophila or Aeromonas veronii. ELISA experiments were conducted to demonstrate the interaction between the IgY antibodies and the bacteria. The kidneys of C. auratus were coated on a Luria–Bertani (LB) medium to evaluate bacterial content. The leukocyte phagocytosis was detected by a cell phagocytosis assay. The serum of C. auratus was used to assess the expression of antioxidant factors, and a qRT-PCR was conducted to evaluate the mRNA expression of inflammatory factors in visceral tissue. Furthermore, histopathology and immunofluorescence analysis were performed to evaluate the structural integrity, apoptosis, and DNA damage of visceral tissues. The results indicated that the live or inactivated A. hydrophila IgY antibodies exhibited passive immune protection rates against A. hydrophila and A. veronii and could recognize these two bacteria in vitro. Additionally, these two IgY improved the phagocytic ability of leukocytes, diminished renal bacterial concentration, and decreased the levels of antioxidant factors and mRNA expression of inflammatory factors. Meanwhile, the two IgY antibodies did not cause any pathology of the kidney, spleen, and intestine, and decreased the levels of DNA damage factor (γH2A.X) and cell apoptosis factor (p53) in renal tissue. Therefore, live and inactivated A. hydrophila IgY antibodies can resist bacterial infections, with live bacteria IgY providing greater protection than inactivated bacteria IgY. Further, A. hydrophila is an aquatic pathogen that causes minimal damage to laying hens, and the immunity of live A. hydrophila conforms to animal welfare. Altogether, live A. hydrophila IgY antibody can serve as a polyvalent passive immune vaccine candidate in aquaculture. Full article

High-fat diets are increasingly used to improve feed efficiency in aquaculture but may deteriorate fillet quality and health; soy isoflavones, plant-derived polyphenols, have emerged as promising modulators of muscle growth, antioxidant defense, and lipid metabolism in fish. This study investigated the effects of dietary soy isoflavone supplementation on myogenesis, collagen synthesis, fatty-acid composition, and antioxidant capacity in muscle of Monopterus albus fed a high-fat diet. Fish were assigned to four diets: control (CON, 6.16% crude fat), high-fat without soy isoflavones (HSIF0, 11.98% crude fat), and high-fat with 50 mg/kg (HSIF50) or 100 mg/kg (HSIF100) soy isoflavones. HSIF0 significantly elevated whole-body/muscle lipids, reduced ΣSFA/ΣMUFA/Σn-3/Σn-6 ratios (p < 0.05), increased Σn-6 (p < 0.05), impaired water-holding capacity/texture (higher losses, lower hardness/cohesiveness/gumminess/chewiness/resilience) (p < 0.05), induced loosely arranged myofibers with enlarged inter-fiber spaces, downregulated myogenesis (upregulated mstn; downregulated myod/tcap/mrf4/mrf5) and collagen genes (ets1/sp1/p4ha1) (p < 0.05), decreased collagen/hydroxyproline (p < 0.05), and weakened antioxidants (higher MDA/H₂O₂; lower T-AOC/GSH; downregulated nrf2/sod/cat/gpx1/gpx8) (p < 0.05). HSIF50 reversed these effects, enhancing ΣPUFA/Σn-3/EPA+DHA (p < 0.05), restoring structure/gene expression (p < 0.05), and boosting antioxidants (p < 0.05). In contrast, HSIF100 partially diminished benefits, indicating dose-dependency. Overall, 50 mg/kg soy isoflavones optimally mitigated high-fat-induced muscle quality decline via lipid remodeling, structural improvement, collagen promotion, and antioxidant enhancement. Full article

Eucommia ulmoides Oliver (E. ulmoides), a traditional medicinal plant, has been widely used for its antioxidant and anti-inflammatory properties. However, its effects on dental tissue regeneration remain largely unexplored. In this study, we investigated the odontogenic potential of E. ulmoides extract in human dental pulp stem cells (hDPSCs). Cell viability was assessed using the cell counting kit-8 (CCK-8) assay, and antioxidant activity was evaluated via the DPPH radical scavenging method. Odontoblast differentiation was examined using Alizarin Red S (ARS) staining, real-time PCR, and Western blot analysis of key differentiation markers, including dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP). Our results demonstrated that E. ulmoides extract enhanced mineralization and upregulated both gene and protein expression of odontoblast differentiation markers in a dose-dependent manner. Furthermore, signaling pathway analysis revealed that E. ulmoides extract activated the SMAD pathway while downregulating ERK and p38 MAPK phosphorylation during odontogenic differentiation. These findings suggest that E. ulmoides extract promotes odontoblast differentiation in hDPSCs and may serve as a promising natural agent for dental tissue regeneration. These findings further underscore its potential clinical relevance as a therapeutic candidate to enhance dental tissue repair and regeneration. Full article