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Evaluating the prognostic significance of HIST1H4C in breast cancer: implications for neoadjuvant therapy
No full textAbstract Breast cancer is a common and highly malignant, currently, HIST1H4C was found to be associated with several human malignancies. The purpose of this study is to investigate tissue HIST1H4C expression in breast cancer and explore its role in disease progression and its interaction with neoadjuvant therapy efficacy. we analyzed tissue HIST1H4C mRNA expression in BC tissue samples from 105 patients received with neoadjuvant therapy using qPCR between 2019 and 2022. Statistical analysis showed that a high expression of HIST1H4C before neoadjuvant therapy was positively related to good responder (CR + PR), while high expression of HIST1H4C after neoadjuvant therapy was negatively related good responder. And HIST1H4C expression was significantly decreased in patients with good responder. In addition, high HIST1H4C expression was also related to ER negative, PR negative, high KI67 expression, high level of histological grade, large tumor size and more lymph node metastases in Curtis database. Furthermore, high HIST1H4C expression before and after-treatment in our center or in database has a positively correlation with poor prognosis. HIST1H4C is the potential biomarker of neoadjuvant therapy and prognosis for breast cancer
Oxysophoridine promotes osteoarthritis repair via GSH system activation and ROS suppression
No full textAbstract Osteoarthritis (OA) is a prevalent joint degenerative disease involving inflammation and oxidative stress, with reactive oxygen species (ROS) driving progression. Restoring joint redox balance mitigates cartilage damage. Osilyhizidine (OSR), from Sophora alopecuroides, has anti-inflammatory/antioxidant properties, but its OA-specific effects and mechanisms were unclear. In vitro experiments assessed OSR’s impact on OA chondrocyte proliferation, repair, and inflammation, focusing on Glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) regulation. A murine OA model validated findings in vivo. OSR showed anti-inflammatory, antioxidant effects and promoted cartilage repair, enhancing chondrocyte functions under inflammation and suppressing pro-inflammation. It upregulated GPX4 (improving ROS detoxification) and SLC7A11 (facilitating glutathione synthesis for redox balance) at transcriptional and protein levels. These were confirmed in mice. OSR alleviates OA by activating GPX4/SLC7A11 to regulate ROS and oxidative stress, emerging as a promising OA therapeutic candidate, offering insights into redox-targeted interventions
Assessment of vitamin E status among patients with newly diagnosed primary knee osteoarthritis in Cameroon
No full textAbstract To determine vitamin E status of patients newly diagnosed with KOA in Yaoundé (Cameroon). An analytical cross-sectional pilot study involving people aged ≥ 40 years, separated into two groups: participants with primary KOA diagnosed based on clinical and radiological elements in accordance with American Rheumatism Association 1986 criteria, and participants without KOA. All participants had a serum alpha-tocopherol assay. Factors associated with vitamin E deficit (˂ 250 µmol/100 mL) were identified in multivariate analysis using logistic regression and present with odds ratio (OR) and its 95% confidence interval. Vitamin E levels were compared according to the Kellgren & Lawrence radiological stage using Kruskal–Wallis’ test. The significance threshold was less than 0.05. The sample comprised 159 participants, aged 53.8 ± 10 years, 67.3% females and 52.8% with primary KOA. Vitamin E deficit was observed in 97.6% participants with KOA and 21.3% without KOA (p < 0.001). It was independently associated with an age ≥ 55 years (OR: 4.2 [1.43; 11.2], p = 0.01), and a frequent vitamin E-rich food consumption (OR: 0.05 [0.003; 0.09], p < 0.001). Vitamin E was significantly lower in participants with KOA comparing with those without (52.2 ± 71.4 versus 452.4 ± 230 µmol/mL, p ˂ 0.001). There was no association between vitamin E levels and Lequesne’s algofunctional index, in contrast to the radiological stage, where a significant decline in vitamin E was observed as the radiological stage progressed. With this high frequency of vitamin E deficiency strongly associated with the radiographic stage of primary KOA, future studies should evaluate its therapeutic implications specifically in this population
In vitro characterization and in ovo embryotoxicity assessment of a triazol-5-one derivative in broiler embryos
No full textAbstract This study is among the pioneering investigations evaluating the embryonic effects of triazol-5-one derivatives administered in ovo to broiler embryos. The synthesized compound, 1-(morpholin-4-yl-methyl)-3-(p-chlorobenzyl)-4-(4-hydroxybenzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one, was examined for its in vitro biological properties and in ovo embryonic safety. The compound is hypothesized to influence embryonic viability in a manner consistent with its structural and biological characteristics. Structural confirmation was achieved through FT-IR, 1H-NMR, and 13C-NMR analyses. In vitro assays showed weak reducing and radical-scavenging capacity but high, stable metal-chelating activity, alongside strong antimicrobial effects. For the in ovo trial, 120 fertilized Ross-308 eggs were assigned to three groups (Control, Dimethyl sulfoxide (DMSO), Experimental; n = 40). On day 17, 0.5 mL of solution was injected into the amniotic cavity, and embryos were monitored until 510 h. Hatchability was 87.5% in the Control group, 80% in the DMSO group, and 0% in the Experimental group. No live chicks hatched in the experimental group, indicating complete embryonic lethality. All embryo losses occurred after injection during incubation, and Levene’s test followed by one-way ANOVA (p = 0.385) confirmed no initial weight differences, indicating a compound-specific effect. The compound’s embryotoxicity may result from strong metal chelation, low antioxidant capacity, oxidative stress, mitochondrial dysfunction, and membrane disruption. These findings provide a basis for defining safe dose ranges, optimizing injection parameters, and assessing the in ovo applicability of related triazole compounds
Clinical relevance of partial HPV genotyping in cervical cancer screening
No full textAbstract Partial human papillomavirus (HPV) genotyping is increasingly used to triage high-risk (HR)-HPV-positive women in national cervical cancer screening. This study evaluated whether separate triage for HPV genotypes 16 and 18 could enhance the effectiveness of Finland’s program. Data from 76,482 women participating in primary HPV screening in Tampere and surrounding municipalities (2012–2023) were analyzed. Partial genotyping identified HPV16, HPV18, and 12 other HR-HPV-types, and the association between genotype and high-grade squamous intraepithelial lesions or worse (HSIL +) detection was assessed. Among 6031 HR-HPV-positive women, HSIL + prevalence was highest in HPV16-positive women (37.3%) followed by HPV18 (26.0%) and other HR-HPV types (20.3%). HSIL + detection declined with age: 26.2%(age 50)(p < 0.001). HPV16 showed the highest persistence upon re-testing (69.6% single; 84.6% co-infections), compared to 53.8% for other HR-HPV types. Among women with NILM cytology, HPV16 infections conferred a significantly higher risk of HSIL + compared to infections with other HR-HPV types. This risk was evident for both single HPV16 infection (OR 2.41;95%CI:1.55–3.75) and HPV16 coinfections (OR 3.86;95%CI:2.14–6.96). These findings support the integration of age-specific strategies and partial HPV16/18 genotyping into Finland’s screening program. A refined triage model, including immediate colposcopy referral for HPV16/18-positive women, could improve patient management and screening efficiency
Multi-responsive, room-temperature self-healing salep-based nanocomposite hydrogels with enhanced mechanical performance as smart biomaterial
No full textAbstract Self-healing hydrogels are advanced materials that can restore their original functionality and properties after mechanical damage, either through intrinsic mechanisms or via external stimuli. However, their widespread application is often limited by challenges such as insufficient mechanical strength, low thermal stability, and inadequate self-healing efficiency. In this study, we developed a novel self-healing hydrogel based on salep. This natural polysaccharide was modified through free radical polymerization using two distinct polymers: polyacrylamide (PAM) and poly)diallyldimethylammonium( chloride (PDADMAC). Additionally, Fe3O4 magnetic nanoparticles (MNPs) were synthesized and incorporated into the hydrogel matrix, imparting magnetic responsiveness. The resulting semi-interpenetrating (semi-IPN) hydrogel network exhibited robust self-healing properties, attributed to dynamic, reversible hydrogen bonds within the polymer chains. The inclusion of Fe3O4 MNPs further facilitated the mobility of polymer chains under an external magnetic field, significantly improving the efficiency and rate of self-repair. The PAM-modified nanocomposite hydrogel achieved an equilibrium swelling ratio of ~ 2300%, while the PDADMAC-based composite reached ~ 1875% at pH = 7. Notably, the semi-IPN structure endowed the hydrogel with self-healing, enabling it to recover its original mechanical integrity within 35 min at room temperature. Combining a natural salep matrix with synthetic polymer networks and Fe3O4 MNPs produced a self-healing hydrogel with markedly improved strength, stability, and functionality. The dynamic hydrogen-bonded network ensures rapid, autonomous repair, while the magnetic component provides tunable responsiveness under external fields. These features, together with High tensile properties and antimicrobial efficacy, suggest broad applicability in biomedical, agricultural, and environmental technologies
Self-care behaviors among Iranian adults with non-alcoholic fatty liver disease based on the health belief model and structural equation modeling
No full textAbstract Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a widespread chronic liver condition globally, with a prevalence of 33% in Iran (35% in males and 37% in females). Understanding health-related behaviors in NAFLD patients is crucial for designing effective interventions. This study is novel in applying the Health Belief Model (HBM) and Structural Equation Modeling (SEM) to examine psychological determinants correlated with self-care behaviors among Iranian adults with NAFLD. A cross-sectional study was conducted with 513 NAFLD patients at the Internal Medicine Clinic of Shahid Motahari Clinic in Shiraz (Persian years 2024–2025) using a questionnaire capturing demographic information and HBM constructs. SEM analysis demonstrated good model fit (CFI = 0.95, TLI = 0.94, RMSEA = 0.038, SRMR = 0.032), indicating that self-care behaviors were primarily correlated with HBM constructs. Perceived susceptibility (β = 0.32, p < 0.001) and self-efficacy (β = 0.31, p < 0.001) showed the strongest positive associations, whereas perceived barriers (β = -0.26, p < 0.001) were negatively correlated with self-care behaviors. Demographic factors, including younger age, higher education, family history, and income, demonstrated smaller but notable associations. These findings highlight that psychological constructs such as self-efficacy, perceived barriers, perceived benefits, and awareness are closely correlated with self-care behaviors, suggesting potential targets for theory-driven interventions to support individuals at risk of NAFLD
The mTOR signaling pathway regulates key steps of mammary gland organoid genesis in a temporal manner
No full textAbstract The development of the mammary gland is a complex process that evolves throughout life. It can undergo drastic changes to support lactation, before involuting back to a rudimentary organ after weaning, in a perfectly orchestrated mechanism. This study aimed to identify the pathways coordinating mammary gland organogenesis, using mouse organoids as a model. In developmental assays, the mechanistic target of rapamycin (mTOR) was shown to be a regulator of cellular lineage determination and branching morphogenesis, acting in a time-dependent manner to control these processes. Indeed, mTOR inhibition during the initial growth phase of organoids abrogated the presence of basal epithelial cells, forcing the expansion of the luminal compartment. At later time points during development, mTOR inhibition promoted branching morphogenesis, increasing the organoid capacity to generate branching/buds. Mechanistically, the mTOR signalling inhibition led to alterations in the expression levels of genes and proteins connected to branching morphogenesis, extracellular matrix remodelling, metabolism, and cell migration. Altogether, this study demonstrates the regulatory functions of mTOR in controlling mammary epithelial cells’ capacity to generate organoids
Environmental toxicant ochratoxin A induces psoriasis based on network toxicology machine learning and molecular docking analyses
No full textAbstract Psoriasis is a chronic skin disease influenced by genetic susceptibility and environmental factors. Ochratoxin A (OTA) is a ubiquitous foodborne mycotoxin known for its immunotoxicity, however, its specific role in psoriasis pathogenesis remains underexplored. This study implemented an integrated systems biology framework that combined network toxicology, machine learning, and molecular dynamics to elucidate the mechanisms of OTA-induced psoriasis. By intersecting OTA-associated targets with psoriasis-related genes, we identified 242 potential targets that were significantly enriched in the IL-17 and TNF signaling pathways. We utilized a weighted gene co-expression network analysis combined with nine machine learning algorithms to identify five hub genes based on their high feature importance and diagnostic robustness: PNP, LCN2, HSPE1, TYMP, and CXCR2, with an area under the curve of 0.988 in the training set and 1.00 in the external validation. These hub genes positively correlated with activated dendritic cells and eosinophils, suggesting that they mediate a pro-inflammatory microenvironment. Molecular docking and dynamics simulations demonstrated stable binding affinities (up to − 8.8 kcal/mol) between OTA and the corresponding proteins. Our findings establish a mechanistic link whereby OTA directly interacts with key regulatory proteins to drive immune dysregulation, providing novel biomarkers and a theoretical basis for managing OTA-induced psoriasis
Research on abnormal pressure of dark shale in the Tiemulike formation of the Yining Sag, Ili basin
No full textAbstract The study of abnormal pressure in the dark shale of the Tiemulike Formation in the Yining Sag of the Ili Basin holds significant importance for its oil and gas exploration. Based on the Acoustic time difference data of shale, the overexposure development interval in the Tiemulike Formation was of the Yining Sag determined. The equilibrium depth method had been adopted to quantitatively calculate the excess pressure and pressure coefficient of dark shale in the Tiemulike Formation for the first time. The distribution map of abnormal excess pressure in single well profiles and well-tie comparison profile had been drawn, and the abnormal excess pressure characteristics of the shale had been fully Analyzed. The results show that the pressure coefficient of the dark shale in Tiemulike Formation is 1.21–1.95, belonging to the weak-high pressure to Ultra-high pressure layers. The excess pressure gradually increased from the top to the deeper layers in the Tiemulike Formation, with three abnormal pressure significantly increased layers. The abnormal excess pressure in Tiemulike Formation is about 5–10 MPa higher than that in the overlying Upper Permian Basiergan Formation, indicating high abnormal pressure characteristics. The horizontal distribution characteristics of abnormal excess pressure in Tiemulike Formation show that the abnormal excess pressure is mostly above 10 MPa, with a highest reaching 29.4 MPa. The Higher abnormal excess pressure has good continuity in the horizontal direction, several high abnormal fluid pressure compartments were formed in the central low-laying area of Yining Sag. The formation of abnormal excess pressure in the shale of the Tiemulike Formation in the Yining Sag was mainly controlled by the hydrocarbon generation expansion of dark shale, as well as the influence of clay mineral diagenesis
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