Search Results (9,365)

Soil salinization constitutes a major constraint on global agricultural production, with marked divergence in salt adaptation strategies between salt-tolerant barley (Hordeum vulgare) and salt-sensitive rice (Oryza sativa). This study systematically investigated the evolution and functional specialization of the C3HC4-type RING zinc finger gene family, known to mediate abiotic stress responses through E3 ubiquitin ligase activity, in these contrasting cereal species. Through comparative genomics, we identified 123 HvC3HC4 genes and 90 OsC3HC4 genes, phylogenetically classified into four conserved subgroups. Differences in C3HC4 genes in phylogenetic relationships, chromosomal distribution, gene structure, motif composition, gene duplication events, and cis-elements in the promoter region were observed between barley and rice. Moreover, HvC3HC4s in barley tissues preferentially adopted an energy-conserving strategy, which may be a key mechanism for barley’s higher salt tolerance. Additionally, we found that C3HC4 genes were evolutionarily conserved in salt-tolerant species. The current results reveal striking differences in salt tolerance between barley and rice mediated by the C3HC4 gene family and offer valuable insight for potential genetic engineering applications in improving crop resilience to salinity stress. Full article

Background: Delays in breast cancer treatment negatively affect prognosis and have increased over time. Data on waiting times in Switzerland are limited. Patients and Methods: This study analyzed cancer registry data from 2003 to 2005 (2628 patients) and 2015 to 2017 (421 patients) to evaluate waiting times for diagnosis, surgery, and radiotherapy; temporal trends; and survival in women with stage I–III invasive breast cancer treated with surgery without chemotherapy. Associations with demographic/clinical factors and overall survival (OS) were assessed using ANOVA, uni-/multivariable regression, Kaplan–Meier, and Cox regression. Results: From 2003 to 2005, mean intervals were biopsy-to-diagnosis 4.3 days, diagnosis-to-surgery 18.8 days, biopsy-to-surgery 26.8 days, and surgery-to-radiotherapy 56.7 days. Longer diagnosis-to-surgery times were associated with metropolitan areas, public hospitals, basic insurance, mastectomy, and older age (all p < 0.001). Radiotherapy delays were also longer in metropolitan areas and after mastectomy (p < 0.001). Between 2003–2005 and 2015–2017, diagnosis-to-surgery times rose in Eastern Switzerland (from 21.3 to 31.2 days), while radiotherapy timing remained stable. Five-year overall survival improved (from 76.7% to 88.4%), but was not significantly impacted by diagnosis-to-surgery intervals. Conclusions: Despite timely surgery in Switzerland (2003–2005), disparities existed, and time to surgery increased by 2015–2017. Reducing waiting times remains important despite no significant short-term OS impact. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, blood–brain barrier dysfunction, oxidative stress (OS), and neuroinflammation. Current treatments provide symptomatic relief, but do not halt the disease’s progression. OS plays a crucial role in AD pathogenesis by promoting Aβ accumulation. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the antioxidant response, influencing genes involved in OS mitigation, mitochondrial function, and inflammation. Dysregulation of NRF2 is implicated in AD, making it a promising therapeutic target. Emerging evidence suggests that adherence to a Mediterranean diet (MD), which is particularly rich in polyphenols from extra virgin olive oil (EVOO), is associated with improved cognitive function and a reduced risk of mild cognitive impairment. Polyphenols can activate NRF2, enhancing endogenous antioxidant defenses. This study employs a computational approach to explore the potential of bioactive compounds in EVOO to modulate NRF2-related pathways in AD. We analyzed transcriptomic data from AD and EVOO-treated samples to identify NRF2-associated genes, and used chemical structure-based analysis to compare EVOO’s bioactive compounds with known NRF2 activators. Enrichment analysis was performed to identify common biological functions between NRF2-, EVOO-, and AD-related pathways. Our findings highlight important factors and biological functions that provide new insight into the molecular mechanisms through which EVOO consumption might influence cellular pathways associated with AD via modulation of the NRF2 pathway. The presented approach provides a different perspective in the discovery of compounds that may contribute to neuroprotective mechanisms in the context of AD. Full article

Prostate cancer accounts for approximately 1.5 million new diagnoses and 400,000 deaths every year worldwide, and demographic projections indicate a near-doubling of both figures by 2040. Despite existing treatments, 10–20% of patients eventually progress to metastatic castration-resistant disease (mCRPC). The median overall survival (OS) after progression to mCPRC drops to 24 months, and efficacy drops severely after each additional line of treatment. Omics platforms have reached advanced levels and enable the acquisition of high-resolution large datasets that can provide insights into the molecular mechanisms underlying PCa pathology. Genomics, especially DDR (DNA damage response) gene alterations, detected via tissue and/or circulating tumor DNA, efficiently guides therapy in advanced prostate cancer. Given recent developments, we have performed a comprehensive literature search to cover recent research and clinical trial reports (over the last five years) that integrate omics along three converging trajectories in therapeutic development: (i) predicting response to approved agents with demonstrated survival benefits, (ii) stratifying patients to receive therapies in clinical trials, (iii) guiding drug development as part of drug repurposing frameworks. Collectively, this review is intended to serve as a comprehensive resource of recent advancements in omics-guided therapies for advanced prostate cancer, a clinical setting with existing clinical needs and poor outcomes. Full article

In this study, the efficacy of super white cement (SWC) to improve organic soils was researched. For stabilization, 10%, 15%, and 20% proportions of SWC were added to organic soil. After improvement with SWC, Atterberg limit testing, standard Proctor tests, triaxial compression tests, and swelling and compressibility tests were performed on the organic soil. Proctor tests showed that stabilization of organic soil with SWC increased maximum dry density (MDD) and optimum moisture content (OMC) values. After stabilization, the unconfined compressional strength values of the soil increased. This increase continued until the 28th day and had a reducing trend after improvement with SWC, linked to time. In addition to the reaction between SWC and OS, the time-dependent behavior of OS also contributed to this behavior. With the increase in SWC proportions, the cohesion intercept and internal friction angle values rapidly increased until the 56th day. This increase began to reduce after the 56th day. After stabilization, the swelling percentage and compressibility values for the soil reduced. The addition of SWC within organic soil appeared to improve the engineering properties of the soil. Full article

Background/Objectives: The clinical potential of antimicrobial peptides (AMPs) against dual threats like antimicrobial resistance (AMR) and cancer is often limited by their high host cell toxicity. Here, we focused on brevinin-2OS (B2OS), a novel peptide from the skin of Odorrana schmackeri with potent haemolytic activity. The objective was to study the structure–activity relationship and optimise the safety via targeted modifications. Methods: A dual-modification strategy involving C-terminal truncation and subsequent N-terminal D-amino acid substitution was employed. The bioactivities and safety profiles of the resulting analogues were evaluated using antimicrobial, haemolysis, and cytotoxicity assays. Result: Removal of the rana box in B2OS(1-22)-NH₂ substantially reduced haemolysis while maintaining bioactivities. Remarkably, the D-leucine substitution in [D-Leu²]B2OS(1-22)-NH₂ displayed a superior HC₅₀ value of 118.1 µM, representing a more than ten-fold improvement compared to its parent peptide (HC₅₀ of 10.44 µM). This optimised analogue also demonstrated faster bactericidal kinetics and enhanced membrane permeabilisation, leading to a greater than 22-fold improvement in its therapeutic index against Gram-positive bacteria. Conclusions: The C-terminal rana box is a primary determinant of toxicity rather than a requirement for activity in the B2OS scaffold. The engineered peptide [D-Leu²]B2OS(1-22)-NH₂ emerges as a promising lead compound, and this dual-modification strategy provides a powerful design principle for developing safer, more effective peptide-based therapeutics. Full article

Background: Angiosarcomas (ASs) represent a heterogeneous and highly aggressive subset of tumors that respond poorly to systemic treatments and are associated with short progression-free survival (PFS) and overall survival (OS). The aim of this study was to develop and validate an immune-related prognostic model—termed the AS score—using data from two independent sarcoma cohorts. Methods: A prognostic model was developed using a previously characterized cohort of 25 angiosarcoma samples. Candidate genes were identified via the Maxstat algorithm (Maxstat v0.7-25 for R), combined with log-rank testing. The AS score was then computed by weighing normalized gene expression levels according to Cox regression coefficients. For external validation, transcriptomic data from TCGA Sarcoma cohort (n = 253) were analyzed. The Immunoscore—which reflects the tumor immune microenvironment—was inferred using the ESTIMATE package (v1.0.13) in R. All statistical analyses were performed in RStudio (v 4.0.3). Results: Four genes—IGF1R, MAP2K1, SERPINE1, and TCF12—were ultimately selected to construct the prognostic model. The resulting AS score enabled the classification of angiosarcoma cases into two prognostically distinct groups (p = 0.00012). Cases with high AS score values, which included both cutaneous and non-cutaneous forms, exhibited significantly poorer outcomes, whereas cases with low AS scores were predominantly cutaneous. A significant association was observed between the AS score and the Immunoscore (p = 0.025), with higher Immunoscore values found in high-AS score tumors. Validation using TCGA sarcoma cohort confirmed the prognostic value of both the AS score (p = 0.0066) and the Immunoscore (p = 0.0029), with a strong correlation between their continuous values (p = 2.9 × 10⁻⁸). Further survival analysis, integrating categorized scores into four groups, demonstrated robust prognostic significance (p = 0.00021). Notably, in tumors with a low Immunoscore, AS score stratification was not prognostic. In contrast, among cases with a high Immunoscore, the AS score effectively distinguished outcomes (p < 0.0001), identifying a subgroup with poor prognosis but potential sensitivity to immunotherapy. Conclusions: This combined classification using the AS score and Immunoscore has prognostic relevance in sarcoma, suggesting that angiosarcomas with an immunologically active microenvironment (high Immunoscore) and poor prognosis (high AS score) may be prime candidates for immunotherapy and this approach warrants prospective validation. Full article

Background: Nigella sativa, known as black cumin, is traditionally used to treat various illnesses. Objective: The current study aims to investigate the potential hepatoprotective and nephroprotective effect of black cumin fractions via per os route in CCl₄-intoxicated Wistar rats. This study used a computational approach to assess the interaction of bioactive compounds with key proteins (CYP P450 3E1, TNF-α, and Cox-2). Methods: Wistar rats were treated with CCl₄ to induce liver injury and with different Nigella sativa fractions (250 mg/Kg) or Sylimarin (50 mg/Kg). Liver and kidney functions were assessed through biochemical markers, hepatic glycogen, malondialdehyde levels, molecular docking, and ADMET analysis to evaluate drug-likeliness. Results: The results revealed that intoxication with CCl₄ induced an elevation in different liver and kidney biochemical parameters such as (ALT, AST, creatinine, urea...) indicating kidney and hepatic toxicity. However, treatment with different Nigella sativa fractions showed a significant improvement in animal body weight and significant amelioration of biochemical markers indicating a protective potential of these fractions against CCl₄-induced intoxication. Furthermore, the molecular docking approach demonstrated high binding affinity with the target proteins. Conclusions: These current findings shed light on the therapeutic potential of Nigella sativa fractions as a promising protective agent of the liver and kidney against CCl₄ intoxication. Full article

Pediatric high-grade glioma (pHGG) is a devastating group of childhood cancers associated with poor outcomes. Traditionally, diagnosis was based on histologic and immunohistochemical characteristics, including high mitotic activity, presence of necrosis, and presence of glial cell markers (e.g., GFAP). With advances in molecular tumor profiling, these tumors have been recategorized based on specific molecular findings that better lend themselves to prediction of treatment response and prognosis. pHGG is now categorized into four subtypes: H3K27-altered, H3G34-mutant, H3/IDH-WT, and infant-type high-grade glioma (iHGG). Molecular profiling has not only increased the specificity of diagnosis but also improved prognostication. Additionally, these molecular findings provide novel targets for individual tumor-directed therapy. While these therapies are largely still under investigation, continued investigation of distinct molecular markers in these tumors is imperative to extending event-free survival (EFS) and overall survival (OS) for patients with pHGG. Full article

Stress granule formation is a type of liquid–liquid phase separation in the cytoplasm, leading to RNA–protein condensates that are associated with various cellular stress responses and implicated in numerous pathologies, including cancer, neurodegeneration, inflammation, and cellular senescence. One of the key components of mammalian stress granules is the DEAD-box RNA helicase DDX3, which unwinds RNA in an ATP-dependent manner. DDX3 is involved in multiple steps of RNA metabolism, facilitating gene transcription, splicing, and nuclear export and regulating cytoplasmic translation. In this study, we investigate the role of the RNA helicase DDX3’s enzymatic activity in shaping the RNA content of ribonucleoprotein (RNP) condensates formed during arsenite-induced stress by inhibiting DDX3 activity with RK-33, a small molecule previously shown to be effective in cancer clinical studies. Using the human osteosarcoma U2OS cell line, we purified the RNP granule fraction and performed RNA sequencing to assess changes in the RNA pool. Our results reveal that RK-33 treatment alters the composition of non-coding RNAs within the RNP granule fraction. We observed a DDX3-dependent increase in circular RNA (circRNA) content and alterations in the granule-associated intronic RNAs, suggesting a novel role for DDX3 in regulating the cytoplasmic redistribution of non-coding RNAs. Full article

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of cases. This study investigates genetic mutations and their associations with overall survival (OS), complete cytoreduction (R0), and platinum response in patients undergoing either primary debulking surgery followed by adjuvant chemotherapy (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT). Genetic analysis was performed on 43 primary HGSOC tumor samples using targeted massive parallel sequencing via next-generation sequencing (NGS). Clinical and molecular data were evaluated collectively and through subgroup comparisons between PDS and NACT cohorts. All analyzed samples harbored genetic alterations. Univariate survival analysis revealed that the total number of mutations (p = 0.0035), as well as mutations in HRAS (p = 0.044), FLT3 (p = 0.023), TP53 (p = 0.03), and ERBB4 (p = 0.007), were significantly associated with poorer OS. Multivariate Cox regression integrating clinical and molecular data confirmed that ERBB4 mutations are independently associated with adverse outcomes. These findings reveal a distinctive mutational landscape between the PDS and NACT groups and suggest that ERBB4 alterations may define a particularly aggressive tumor phenotype. This study contributes to a deeper understanding of HGSOC biology and may support the development of novel therapeutic targets and personalized treatment strategies in the context of precision oncology. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. Methods: A systematic literature search was carried out for the period between October 2016 to September 2024. Phase II and III randomized trials evaluating ICI monotherapy, ICI–chemotherapy combinations, and dual ICI regimens in patients with advanced NSCLC were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). Results: PD-1-targeted therapies demonstrated superior OS compared to PD-L1-based regimens, with cemiplimab monotherapyranking highest for OS benefit (posterior probability: 90%), followed by sintilimab plus platinum-based chemotherapy (PBC) and pemetrexed—PBC. PFS atezolizumab plus bevacizumab and PBC, and camrelizumab plus PBC were the most effective regimens. ICI–chemotherapy combinations achieved higher ORRs but were associated with greater toxicity. The most favorable safety profiles were observed with cemiplimab, nivolumab, and avelumab monotherapy, while atezolizumab plus PBC and sugemalimab plus PBC carried the highest toxicity burdens. Conclusions: In PD-L1-unselected advanced NSCLC, PD-1 blockade—particularly cemiplimab monotherapy—and rationally designed ICI–chemotherapy combinations represent the most efficacious treatment strategies. Balancing efficacy with safety remains critical, especially in the absence of predictive biomarkers. These findings support a patient-tailored approach to immunotherapy and highlight the need for further biomarker-driven and real-world investigations to optimize treatment selection. Full article

Background/Objective: Accurately identifying women at high risk for preterm birth among those with threatened preterm labor (PTL) is crucial for effective interventions or tocolytic management to reduce preterm birth and its complications. This study aimed to determine the predictive value of cervical elastography for preterm delivery before 37 weeks of gestation in patients with threatened PTL and a cervical length greater than 15 mm. Methods: This prospective cohort study included pregnant women presenting with threatened PTL at between 24 and 34 weeks gestation. All participants underwent cervical elastography at diagnosis. We compared cervical elastography parameters between women who delivered spontaneously preterm (<37 weeks) and those who delivered at full term and assessed the ability of these parameters to predict spontaneous preterm delivery. Results: Among the 107 enrolled individuals with threatened PTL and a cervical length of ≥15 mm, 55 (42%) experienced preterm birth (<37 weeks). Internal os stiffness (IOS), internal-to-external os stiffness ratio (IOS/EOS ratio), and elasticity contrast index (ECI) were significantly associated with a risk of preterm birth compared to full-term birth. The IOS/EOS ratio was associated with 10-fold higher odds of preterm birth at < 37 weeks (95% confidence interval [CI], 1.82–59.98), and ECI was associated with 1.5-fold higher odds (95% CI, 1.01–2.37). The IOS/EOS ratio demonstrated good predictive value (area under the curve (AUC) = 0.678) and the combination of CL ≤ 25 mm and the IOS/EOS ratio had good diagnostic performance for predicting preterm birth (AUC = 0.708). Conclusions: Cervical elastography using the E-Cervix™ system appears to improve the ability to predict preterm birth in pregnant women with threatened PTL and a cervical length greater than 15 mm. Full article

Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058. Full article

CAPOX and FOLFOX are widely used chemotherapy regimens for colorectal cancer (CRC). The superiority of one regimen over the other in a real-world setting (RWE) could have significant clinical implications given their common use, but such RWE is limited. This study analyzed provincial database records of 13,461 Canadian patients treated from 2005 to 2017. The primary outcomes were rates of Emergency Department visits and/or hospitalizations (ED/H) and overall survival (OS). CAPOX was used less frequently (8.4%) than FOLFOX (91.6%), often in older patients (p < 0.003 for Stage I–III; p < 0.001 for Stage IV). CAPOX recipients had shorter treatment durations (median 15 vs. 20 weeks, p = 0.002) and higher unadjusted ED/H rates (60.8% vs. 50.9%, p < 0.001), though this difference was nonsignificant on multivariate analysis (MVA) (HR 1.05 (0.92, 1.20), p = 0.466). Patients receiving CAPOX had worse OS than those on FOLFOX, (5-year OS 70.1% vs. 77.2% (p < 0.001) non-metastatic; 16.6% vs. 33.2% (p < 0.001) metastatic). MVA confirmed inferior OS with CAPOX (HR 1.42, p < 0.001). Other predictors of shorter OS included older age, male sex, comorbidities, rural residence, and lower income. This administrative data is at risk of bias but highlights the need for careful patient selection and informed treatment decision making. Full article