Search Results (517)

Background: Posttraumatic growth (PTG) refers to positive psychological change following trauma. While its psychological aspects are well-documented, the biological mechanisms remain unclear. Epigenetic changes, such as DNA methylation (DNAm), may offer insight into PTG’s neurobiological basis. Aims: This study aimed to identify epigenetic markers associated with PTG using an epigenome-wide association study (EWAS), the first of its kind in a trauma-exposed population. Methods: A longitudinal EWAS design was used to assess DNAm before and after trauma exposure in first-year paramedicine students (n = 39). Genome-wide methylation data were analyzed for associations with PTG, applying epigenome-wide and gene-wise statistical thresholds. Pathway enrichment analysis was also conducted. Results: The study identified two CpGs (cg09559117 and cg05351447) within the PCDHA1/PCDHA2 and PDZD genes significantly associated with PTG at the epigenome-wide threshold (p < 9.42 × 10^–8); these were replicated in an independent sample. DNAm in 5 CpGs across known PTSD candidate genes ANK3, DICER1, SKA2, IL12B and TPH1 were significantly associated with PTG after gene-wise Bonferroni correction. Pathway analysis revealed that PTG-associated genes were overrepresented in the Adenosine triphosphate Binding Cassette (ABC) transporters pathway (p = 2.72 × 10⁻⁴). Conclusions: These results identify genes for PTG, improving our understanding of the neurobiological underpinnings of PTG. Full article

This paper presents TwinP2G, a software application for optimal planning of investments in power-to-gas (PtG) systems. TwinP2G provides simulation and optimization services for the techno-economic analysis of user-customized energy networks. The core of TwinP2G is based on power flow simulation; however it supports energy sector coupling, including electricity, green hydrogen, natural gas, and synthetic methane. The framework provides a user-friendly user interface (UI) suitable for various user roles, including data scientists and energy experts, using visualizations and metrics on the assessed investments. An identity and access management mechanism also serves the security and authorization needs of the framework. Finally, TwinP2G revolutionizes the concept of data availability and data sharing by granting its users access to distributed energy datasets available in the EnerShare Data Space. These data are available to TwinP2G users for conducting their experiments and extracting useful insights on optimal PtG investments for the energy grid. Full article

Endometriosis is a chronic estrogen-dependent condition with limited treatment options, often requiring surgery and long-term hormonal therapy that may impair ovarian function. Despite advancements in gene therapy for other diseases, its application in endometriosis remains largely unexplored. This study aimed to evaluate the potential of adeno-associated virus (AAV) vectors for targeted gene therapy in endometriosis. We screened multiple AAV serotypes for infectivity in primary human ectopic and eutopic endometrial cells as well as normal ovarian stromal cells. AAV serotype 3 (AAV3) demonstrated selective infectivity toward endometrial cells while sparing ovarian tissue. AAV3-mediated delivery of small interfering RNA targeting estrogen receptor 2 reduced Estrogen receptor beta (ERβ) expression to 27% in ectopic and 49% in eutopic cells. Under estradiol and inflammatory stimulation, ERβ knockdown led to modest reductions in cellular metabolic activity in eutopic cells, whereas effects in ectopic cells did not reach statistical significance. Dual targeting of ERβ and prostaglandin-endoperoxide synthase 2 (PTGS2) showed numerically lower metabolic activity than controls under some conditions but without consistent statistical significances. These findings suggest that AAV3 can serve as an ovary-sparing, endometriosis-specific vector that facilitates gene silencing while yielding limited phenotypic effects. This gene delivery system may provide a basis for developing future gene-based therapies for endometriosis. Full article

While Moringa oleifera Lam. (MO) extracts are known to have various bioactive properties, including anti-inflammatory properties, the components responsible still remain to be identified. This study explores the protective effects of the MO component, 7-octenoic acid (7OCT) in LPS-stimulated THP-1 macrophage inflammatory responses. The compound significantly downregulated the production of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as the expression of inflammation-related genes NFKB1, PTGS2, and NOS2. Additionally, it inhibited the nuclear translocation of NF-κB p65, a key transcription factor of inflammatory signaling cascade. Effects on oxidative stress showed that 7OCT inhibited LPS-induced NADPH oxidase 2 (NOX2) component genes including CYBB, CYBA, NCF1, NCF2, and NFE2L2, along with phosphorylated NOX2 and p47^phox proteins. The compound reduced the expression of TP53, BAX, CASP3, and CASP7, while enhancing BCL2 expression and Bcl-2 protein levels, suggesting an effect on apoptosis. Decreased levels of BAX, caspase-3, and cleaved caspase-3 proteins further confirmed its anti-apoptotic effect. Our findings suggest that 7OCT exhibits strong anti-inflammatory, antioxidant, and anti-apoptotic properties. Full article

Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with limited effective treatment options. This study aimed to explore the therapeutic potential of novel pyrazole N-aryl sulfonate derivatives (compounds 4b, 4d, and 5f) as selective cyclooxygenase-2 (COX-2; prostaglandin-endoperoxide synthase 2, PTGS2) inhibitors in OSCC. Using CCK-8 and Transwell assays, we evaluated the anti-proliferative and anti-migratory effects of these compounds on CAL-27 and SAS cell lines, while apoptosis was assessed by Hoechst 33342 staining and flow cytometry. Molecular mechanisms were investigated through RT-qPCR, Western blot, and ELISA, focusing on COX-2, MMP2, MMP9, BCL2, BAX, and the JAK/STAT3 pathway. The results demonstrated that compounds 4b, 4d, and 5f significantly inhibited cell proliferation and migration, induced apoptosis, and downregulated the expression of COX-2 and its downstream targets. Notably, these compounds exhibited lower cytotoxicity in VERO cells, indicating favorable biological safety. In conclusion, our findings suggest that pyrazole N-aryl sulfonate derivatives effectively suppress OSCC cell growth and migration by targeting COX-2 and the JAK/STAT3 pathway, highlighting their promise as potential targeted therapeutics for OSCC. Full article

To investigate how sweating–drying processing affects the components, antioxidant activity, and hepatoprotective mechanisms of Eucommia ulmoides (EUB) against acute liver injury (ALI), this study constructed a “processing–active components–ALI targets” network. Eight processed EUB samples were analyzed using HPLC fingerprinting, multi-assay antioxidant tests (DPPH/ABTS·+/pyrogallol), network pharmacology, and molecular docking. Sweating–drying significantly altered EUB’s chemical profile, with HPLC fingerprint similarities ranging from 0.715 to 1.000, the lowest being for FG4 (40 °C dried after sweating) and FD (freeze-dried after sweating). Key components (chlorogenic acid (CA), pinoresinol diglucoside (PDG), aucubin (AU), geniposidic acid (GPA)) varied: XS (sun-dried) had the highest CA/PDG, while FG4 showed increased AU/GPA. FY (shade-dried after sweating) exhibited the strongest free radical scavenging (DPPH/ABTS·+/pyrogallol IC₅₀ = 0.828, 0.134, 14.200 mg/mL), which correlated with CA/PDG/liriodendrin (PD) synergy. Network pharmacology identified 205 EUB-ALI intersection targets (core: TNF, PTGS2, GAPDH) and the AGE-RAGE pathway; molecular docking confirmed strong CA/PDG binding to GAPDH/PTGS2. This study clarifies how processing regulates EUB’s components and their links to antioxidant and hepatoprotective effects, providing scientific support for EUB’s clinical application against ALI. Full article

The reliability of molecular diagnostic and prognostic tools is contingent on the quality of biospecimens, which are often collected during surgical procedures. This study investigated the impact of surgical manipulation on gene expression in the urinary bladder mucosa during radical cystectomy. Seventeen patients with urinary bladder cancer were enrolled, and paired pre- and post-surgery biopsies were analyzed. Pre-surgical biopsies were obtained in situ under anesthesia, while post-surgical biopsies were collected ex vivo following bladder removal. Total RNA was extracted, and gene expression was assessed using qPCR arrays, measuring the expression of 374 inflammation-related genes. The findings from the exploratory phase were further validated by analyzing key genes in an independent patient cohort using TaqMan^® gene-specific assays. Exploratory analysis revealed significant differential expression in 27 genes, with key genes such as IL6, FOS, and PTGS2 being upregulated post-surgery. Validation of five selected genes in an independent cohort confirmed these findings. This study reinforces the necessity of accounting for surgery-induced alterations in gene expression when analyzing tissue samples collected intraoperatively. By elucidating the molecular impact of surgical interventions, this work provides critical insights for refining experimental methodologies and enhancing the interpretability of gene expression studies in clinical and research settings. Full article

Ferroptosis is a new mode of cell death, which is characterized by inducing the accumulation of lipid peroxides dependent on iron ions and reactive oxygen species. It has been found that ferroptosis can lead to follicle atresia by promoting granulosa cell death and increasing its reactive oxygen species content, but the specific mechanism has not been elucidated. Through transcriptome sequencing, we found that ferroptosis markers and related genes were upregulated in porcine atretic follicles. PTGS2 was found to be differentially expressed between atretic and healthy follicles. By inhibiting NF-κB nuclear translocation, inhibition of the PTGS2 gene expression reduced the degree of ferroptosis in granulosa cells and rescued granulosa cell death and oxidative stress caused by ferroptosis. Therefore, we propose that the NF-κB/PTGS2 axis plays a key role in ferroptosis-induced granulosa cell death, leading to follicular atresia. Melatonin, a neurohormone secreted by the pineal gland of the upper thalamus, is involved in the regulation of various metabolic, immune, reproductive, and other processes. In the ferroptosis treatment group, melatonin treatment alleviated the degree of ferroptosis (downregulation of ferroptosis marker genes and markers) and decreased the expression of PTGS2. In summary, we have demonstrated that melatonin inhibits ferroptosis via the NF-κB/PTGS2 axis in granulosa cells. Full article

Background: This study explores post-traumatic growth (PTG) among parents of childhood cancer survivors (CCSs), a group often underrepresented in research. Method: A convergent parallel mixed-methods design integrating Bayesian Multilevel Latent Class Analysis and Thematic Analysis was utilized in a longitudinal study involving 58 caregivers (50 mothers, 8 fathers) from the Children’s Clinical University Hospital in Riga. Quantitative data were collected at diagnosis using the Psychosocial Assessment Tool (PAT) and Big Five Inventory-10 (BFI-10). Follow-up assessments post-treatment included the Responses to Stress Questionnaire (RSQ), Impact of Event Scale-Revised (IES-R), and the Post-traumatic Growth Inventory (PTGI). Qualitative data were collected through structured interviews. Results: A 2-class model distinguished parents with low PTG from those with moderate to high PTG. Change in values, detachment from trivial stressors, and acceptance of life emerged as key indicators of growth. PTG was not significantly correlated with overall post-traumatic stress symptoms, but engagement coping strategies showed a positive association with PTG and personality traits like extraversion and openness. Conclusions: The mixed methods approach revealed sample-specific PTG elements not reflected in standardized tools. Initial perceptions of the cancer diagnosis shaped psychological outcomes, with PTG facilitated by adaptive coping, self-reflection, support, emotional disclosure, and psychological struggle. This study offers the first insights into PTG among Latvian parents of CCSs, a previously unexplored area. Full article

This quantitative study examined the relationships between perceived social support, psychological resilience, and posttraumatic growth (PTG) among university students affected by the 6 February 2023 earthquakes in Türkiye. Utilizing a correlational design, the study tested whether psychological resilience mediated the relationship between perceived social support and PTG. The sample consisted of 769 undergraduate students from Kahramanmaraş Sütçü İmam University and Malatya Turgut Özal University, selected through convenience sampling. Data were collected via standardized instruments: the Multidimensional Scale of Perceived Social Support, the Resilience Scale for Adults, and the Posttraumatic Growth Inventory. A mediation analysis was conducted using the path analysis and bootstrapping methods with the IBM AMOS 24.0 software. The results revealed that perceived social support positively predicted both psychological resilience and PTG, and psychological resilience positively predicted PTG. The mediation analysis confirmed that psychological resilience partially mediated the relationship between perceived social support and PTG. Additionally, significant differences in PTG, resilience, and perceived social support levels were found across gender, housing conditions, psychological impact levels, and access to support. Notably, female students, those who lost loved ones, and those who received psychological or family support reported higher PTG levels. The results emphasize the critical role of social and individual resources in trauma adaptation. It is recommended that post-disaster psychosocial interventions prioritize strengthening both perceived social networks and individual resilience capacities to foster posttraumatic growth in affected populations. Full article

The endometrial immune response in postpartum cows is key to maintaining uterine health and preventing inflammatory diseases such as metritis and endometritis. Appropriate management strategies and diets that enhance the immune response are crucial during the transition period; therefore, diets rich in omega-3 fatty acids have been proposed for their potential beneficial effects on cows. Docosahexaenoic acid (DHA) is an omega-3 fatty acid with anti-inflammatory effects in immune cells; however, its effects on bovine endometrial immunity are not fully known. This study aimed to determine the effect of DHA on the inflammatory response in bovine endometrial (BEND) cells. BEND cells were incubated with DHA without or with lipopolysaccharide (LPS), and the mRNA expressions of prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin (IL)-6, and CXCL8 were analyzed using RT-qPCR. The protein amount of IL-6, or CXCL8, and Resolvin D1 (RvD1) in the cell culture medium were analyzed using ELISA. DHA significantly reduced the expression of LPS-induced IL-6 and PTGS2 but increased LPS-induced CXCL8 expression. In addition, DHA reduced LPS-induced ERK1/2 and Akt phosphorylation, as assessed by immunoblotting. DHA increased the production of RvD1, a metabolite of DHA, at 8 and 24 h. In addition, RvD1 reduced LPS-induced CXCL8 production and increased the phosphorylation of ERK1/2 and Akt. Finally, changes in metabolite levels, such as an increase in 2-hydroxypyridine in DHA-treated cells, were obtained using a metabolomic assay. In conclusion, DHA reduced IL-6 and PTGS2 mRNA expression and IL-6 protein release and increased RvD1 levels in bovine endometrial cells, which suggest that DHA could have beneficial effects on endometrial immunity. The increase in CXCL8 mRNA expression and protein release induced by DHA remains to be studied; however, it could play a role in the innate defensive mechanisms of phagocytes. Full article

As a highly disabling chronic inflammatory disease, rheumatoid arthritis (RA) necessitates novel interventions. Liupao tea is a traditional Chinese dark tea known for its favorable anti-inflammatory properties. This study aims to elucidate the active ingredients and action mechanisms underlying the therapeutic effects of Liupao tea extract (LPTE) in RA. LPTE was preliminarily characterized by LC-MS technology. Network pharmacology and molecular docking predicted anti-RA compounds, targets, and pathways, with key compounds identified using chemical standards. The effect of LPTE on the collagen-induced arthritis mouse model was evaluated through serum biochemical analysis, micro-CT imaging, and histopathological analyses. Integrated serum metabolomics, 16S rRNA sequencing, MetOrigin analysis, SCFA metabolomics, and quantitative real-time PCR elucidated gut–joint axis mechanisms. LPTE effectively attenuated RA symptoms by reducing bone destruction and joint inflammation. Notably, LPTE reshaped gut microbiota by enriching key families such as Monoglobaceae, Eggerthellaceae, and Desulfovibrionaceae, thereby promoting SCFA production. Increased SCFA levels enhanced intestinal barrier integrity and exerted joint-protective and anti-inflammatory effects by upregulating tight junction proteins and activating SCFA receptors. LPTE also modulated arachidonic acid metabolism by affecting key genes such as Alox5, Ptgs2, and Cbr1. These effects collectively reduced the levels of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines in joints. Additionally, quercetin, luteolin, ellagic acid, and kaempferol were identified as major anti-RA bioactive compounds in LPTE. Taken together, this study provides preliminary evidence that LPTE mitigates RA by regulating the gut–joint axis mediated via fatty acid metabolism. Full article

Witches’ broom disease of blue palo verde (Parkinsonia florida) was reported more than sixty years ago. Characteristic symptoms consist of dense clusters of shortened, brittle branches and stunted leaves. The suspect causal agent has been identified as palo verde broom virus (PVBV), genus, Emaravirus, family, Fimoviridae. Here, the first complete PVBV genome sequence was determined, and virus small interfering RNAs (vsiRNAs), primary metabolites, and phytohormone profiles were characterized from infected palo verde leaves, adventitious shoots, flowers, and seeds. Based on pairwise distances, PVBV RNAs 1–4 shared 54–65% nucleotide identity and 19–51% amino acid similarity, respectively, with other emaraviruses, while PVBV RNA 5 shared no sequence homology with any emaravirus. The 21–24-nt virus-derived vsiRNAs, indicative of post-transcriptional gene silencing (PTGS), represented nearly the entire PVBV genome in flowers, leaves, seeds, and adventitious shoots; however, PVBV RNA 3 and RNA 4 were most heavily targeted in all plant parts. Evidence that six major phytohormones were altered in PVBV-infected compared to virus-free trees indicated that emaravirus-infected trees mount classical defense responses to virus infection and/or eriophyid mite infestations. Detection of PVBV RNA genome segments 1–5, accumulation of predominantly 21-nt vsiRNAs, homologous to the PVBV genome and transcripts, and altered levels of phytohormones and metabolites in PVBV-infected trees strongly implicate PVBV as the causal agent of witches’ broom disease. Full article

Isoliquiritigenin (ISL) is a type of chalcone that widely exists in medicinal plants of the Leguminosae family and exhibits a remarkable anti-ischemic stroke (IS) effect. However, the anti-IS mechanisms of ISL remain to be systematically elucidated. In this study, network pharmacology was used to predict potential targets related to the anti-IS effect of ISL. The binding ability of ISL to potential core targets was further analyzed by molecular docking and molecular dynamics (MD) simulations. By establishing an oxygen–glucose deprivation/reoxygenation (OGD/R)-induced HT22 cell model, the anti-IS mechanisms of ISL were investigated via RT-qPCR and Western Blot (WB). As a result, network pharmacology analysis revealed that APP, ESR1, MAO-A, PTGS2, and EGFR may be potential core targets of ISL for anti-IS treatment. Molecular docking and molecular dynamics simulation results revealed that ISL can stably bind to the five potential core targets and form stable complex systems with them. The results of the cell experiments revealed a significant anti-IS effect of ISL. Additionally, mRNA and protein expression levels of APP, MAO-A and PTGS2 or ESR1 in the ISL treatment group were significantly lower or higher than those in the OGD/R group In conclusion, ISL may improve IS by regulating the protein expression levels of APP, ESR1, MAO-A, and PTGS2. Full article

Existing heuristic algorithms are based on inspiration sources and have not yet done a good job of basing themselves on optimization principles to minimize and utilize historical information, which may lead to low efficiency, accuracy, and stability of the algorithm. To solve this problem, a personalized-template-guided intelligent evolutionary algorithm named PTG is proposed. The core idea of PTG is to generate personalized templates to guide particle optimization. We also find that high-quality templates can be generated to guide the exploration and exploitation of particles by using the information of the population particles when the optimal value remains unchanged, the knowledge of population distribution changes, and the dimensional distribution properties of particles themselves. By conducting an ablation study and comparative experiments on the challenging CEC2022 test and CEC2005 test functions, we have validated the effectiveness of our method and concluded that the stability and accuracy of the solutions obtained by PTG are superior to other algorithms. Finally, we further verified the effectiveness of PTG through four engineering problems. Full article