Search Results (2,629)

Combination chemotherapy regimens are commonly employed to treat advanced gastric adenocarcinoma (GAC), yet median survival remains less than one year. Nab-paclitaxel has demonstrated significant antitumor activity in preclinical GAC models. Overexpression of growth factors and their receptors is prevalent in GAC and contributes to its pathophysiology, with aberrant activation of the HGF/c-Met pathway reported in up to 50% of patients. We hypothesized that merestinib, a small-molecule inhibitor of c-Met, Axl, and DDR1/2, would enhance the therapeutic response to nab-paclitaxel in GAC. In high c-Met–expressing MKN-45 peritoneal dissemination xenografts in female NOD/SCID mouse models, animal survival was 17 days in controls, 37 days with nab-paclitaxel (118% increase), 24 days with merestinib (41% increase), and 43 days with the combination (153% increase), demonstrating significantly enhanced survival compared with either monotherapy. In MKN-45 subcutaneous xenografts, tumor volumes in the control, nab-paclitaxel, merestinib, and combination groups were 503 mm³, 115 mm³, 91 mm³, and −9.7 mm³ (indicating tumor regression), respectively. In low c-Met-expressing SNU-1 xenografts, tumor volumes were 219 mm³, 105 mm³, 131 mm³, and 57 mm³, respectively. IHC analysis of tumor cell proliferation and microvessel density in MKN-45 tumors supported these findings. In vitro, nab-paclitaxel and merestinib each reduced cell proliferation in GAC-associated cells, with enhanced inhibitory effects when used in combination. In MKN-45 cells, merestinib increased the expression of pro-apoptotic proteins and decreased phosphorylation of c-Met, EGFR, IGF-1R, ERK, and AKT. These results indicate that combining merestinib with nab-paclitaxel may represent a promising therapeutic strategy to improve outcomes for patients with GAC. Full article

To effectively manage and conserve ecosystems, it is crucial to understand how vegetation changes over time and space and what drives these changes. The Normalized Difference Vegetation Index (NDVI) is a key measure of plant growth that is highly sensitive to climate variations. Despite its importance, there has been limited research on vegetation changes in the upper sections of the Irtysh River. In our study, we combined various datasets, including NDVI, temperature, precipitation, soil moisture, elevation, and land cover. We conducted several analyses, such as Theil–Sen median trend analysis, Mann–Kendall trend and mutation tests, partial correlation analysis, the geographical detector model, and wavelet analysis, to reveal the region’s pronounced warming and moistening trend in recent years, the response relationship between NDVI and the climate, and the primary drivers influencing NDVI variations. We also delved into the spatiotemporal evolution of NDVI and identified key factors driving these changes by analyzing atmospheric circulation patterns. Our main findings are as follows: (1) Between 1901 and 2022, the area’s temperature rose by 0.018 °C/a, with a noticeable increase in the rate of warming around 1990; precipitation increased by 0.292 mm/a. From 1950 to 2022, soil moisture exhibited a steady increase of 0.0002 m³ m⁻³/a. Spatial trend distributions indicated that increasing trends in temperature and precipitation were evident across the entire region, while trends in soil moisture showed significant spatial variation. (2) During 1982 to 2022, the vegetation greening trend was 0.002/10a, indicating a gradual improvement in vegetation growth in the study area. The spatial distribution of monthly average NDVI values revealed that the main growing season of vegetation spanned April to November, with peak NDVI values occurring in June–August. Combined with serial partial correlation and spatial partial correlation analysis, temperatures during April to May effectively promoted the germination and growth of vegetation, while soil moisture accumulation from June to August (or January to August) effectively met the water demand of vegetation during its growth process, with a significant promoting effect. Geographical detector results demonstrate that temperature exhibits the strongest explanatory power for NDVI variation, whereas land cover has the weakest. The synergistic promotional effect of multiple climatic factors is highly pronounced. (3) Wavelet analysis revealed that the periodic characteristics of NDVI and climate variables over a 2–15-year timescale may have been associated with the impacts of atmospheric circulation. Taking NDVI and climatic factors from June to August as an example, before 2000, temperature was the dominant influencing factor, followed by precipitation and soil moisture; after 2000, precipitation and soil moisture became the primary drivers. The North Atlantic Oscillation (NAO) and Arctic Oscillation (AO) were the primary atmospheric circulation patterns influencing vegetation variability in the region. Their effects were reflected in the inverse relationship observed between NAO/AO indices and NDVI, with typical phases of high and low NDVI closely corresponding to shifts in NAO and AO activity. This study helps us to understand how plants have been changing in the upper parts of the Irtysh River. These insights are critical for guiding efforts to develop the area in a way that is sustainable and beneficial for the environment. Full article

Background and Objectives: Dysglycemia is a major determinant of adverse outcomes in COVID-19, yet the separate contributions of poor glycemic control and glycemic variability (GV) remain incompletely defined. We conducted a systematic review and meta-analysis of observational cohort studies (both prospective and retrospective) to quantify the impact of chronic hyperglycemia and glucose instability on disease severity, intensive care requirements, and mortality in patients with COVID-19. Materials and Methods: We searched PubMed, Scopus, and Web of Science from January 2020 to October 2024 for observational cohort studies reporting clinically relevant COVID-19 outcomes stratified by glycemic control or GV. Dysglycemia definitions varied across studies (HbA1c-based chronic hyperglycemia, fasting glucose, or admission/in-hospital hyperglycemia). GV was assessed using metrics including mean amplitude of glycemic excursions (MAGE), standard deviation (SD), coefficient of variation (CV), or maximum daily glucose difference. Twelve studies met inclusion criteria and were included in qualitative synthesis; five studies were eligible for quantitative synthesis of clinical outcomes. Random-effects DerSimonian–Laird models were applied due to anticipated clinical heterogeneity. Heterogeneity was evaluated using Cochran’s Q, τ², and I² statistics. Results: Overall, 12 observational studies (9 prospective and 3 retrospective cohorts; n = 1,008,310 patients) were included. In quantitative analyses of five eligible cohorts, poor glycemic control was associated with a significantly increased risk of severe or critical COVID-19 (pooled RR = 1.75, 95% CI: 1.45–2.11; I² = 29%), ICU admission (RR = 1.54, 95% CI: 1.18–2.01), and mechanical ventilation (RR = 1.72, 95% CI: 1.31–2.26). Three studies evaluating GV demonstrated a strong association with adverse outcomes (pooled RR = 2.07, 95% CI: 1.71–2.50; I² = 0%); this low heterogeneity should be interpreted cautiously given the limited number of studies. GV remained associated with mortality in multivariable models, indicating that glycemic variability is separately associated with mortality as a clinically relevant prognostic risk marker in hospitalized COVID-19 patients. Conclusions: Both chronic hyperglycemia and elevated glycemic variability are each associated with increased risk of severe COVID-19 outcomes. Glycemic variability appeared to be a consistent, low-heterogeneity prognostic marker of mortality, being separately associated with higher death risk in hospitalized COVID-19 patients, highlighting its potential utility as a dynamic metabolic biomarker. Early identification and targeted management of dysglycemia—especially glucose instability—may improve prognosis in hospitalized COVID-19 patients. PROSPERO: CRD420251250718. Full article

Background: Metabolic syndrome (MetS) is a pathological condition characterized by the co-occurrence of multiple metabolic abnormalities. The affected population is increasingly shifting toward younger age groups. Emerging digital health technologies, arising from advances in digital society, offer novel methodological tools for lifestyle-based interventions targeting metabolic risk. This systematic review aims to evaluate the effectiveness of emerging digital health technologies based on dietary and physical activity regulation in improving MetS-related outcomes among adolescents, including school-aged children. Methods: This review followed the PRISMA guidelines, systematically searched PubMed, Web of Science, Embase, MEDLINE, and Scopus, and screened eligible studies based on the PICO framework. Results: A total of 12 randomized controlled trials published between 2012 and 2025 were included in the analysis. Single device interventions (5/12) and dual device combinations (5/12) were the predominant approaches used in current digital health technology applications. Intervention content primarily focused on either physical activity alone (5/12) or combined exercise and nutrition interventions (7/12), with most programs lasting 3–6 months (7/12). Across the included digital health interventions, 13 MetS-related measures were assessed, including anthropometric/body composition measures (BMI, BMI z-score, WC, WHR, WHtR, and VFA), blood pressure measures (SBP/DBP), and biochemical markers (BG, HOMA-IR, TG, TC, HDL-C, and LDL-C). Conclusions: The available evidence supports the potential of digital health technologies to improve MetS-related outcomes. Although the selection of biochemical markers varied across studies, the findings highlight the importance of combined exercise and nutrition interventions or physical activity of moderate to high intensity in improving MetS. These results underscore the value of digital health technologies in elucidating the complex interactions among diet, physical activity, and metabolic responses. Overall, these findings support integrating digital health technologies into adolescent lifestyle interventions to facilitate more personalized monitoring and behavior support, and to potentially improve MetS-related outcomes. By promoting timely improvements in these outcome measures, such digital health interventions may have potential longer term implications for chronic disease prevention. Full article

SATB2 (special AT-rich binding protein 2) functions as a chromatin-associated epigenetic regulator that modulates gene expression, in part by serving as a transcriptional cofactor. This study assessed whether SATB2 overexpression is sufficient to promote in vitro transformation of human mesothelial cells and whether SATB2 suppression in mesothelioma cancer stem cell (CSC)–enriched populations is associated with altered chemoresistance. SATB2 expression was high in human malignant pleural mesothelioma (MPM) cell lines but absent in Met5A mesothelial cells. Ectopic SATB2 expression in Met5A cells was associated with acquisition of malignant and stem cell–like phenotypes, including increased expression of stem cell markers and pluripotency-associated factors, as well as anchorage-independent growth in soft agar and spheroid formation in suspension culture. In contrast, Met5A cells transduced with an empty vector did not form colonies or mesospheres. SATB2 overexpression in Met5A cells was also associated with increased motility, migration, and invasion, accompanied by induction of epithelial–mesenchymal transition (EMT)–related transcription factors relative to empty vector controls. Conversely, shRNA-mediated SATB2 knockdown in an MPM cell line attenuated proliferation, EMT-associated features, and CSC-like characteristics. Chromatin immunoprecipitation assays identified SATB2 occupancy at promoter regions of Bcl2, XIAP, KLF4, c-Myc, NANOG, and SOX2, consistent with a role in transcriptional regulation of genes linked to transformation, pluripotency, cell survival, proliferation, and EMT. In CSC-enriched cells, SATB2 inhibition was associated with increased sensitivity to cisplatin and pemetrexed, concomitant with reduced OCT4 and SOX2 expression. Collectively, these findings support SATB2 as a candidate therapeutic target in MPM and suggest that SATB2 suppression may enhance chemotherapy response when combined with standard agents. Full article

Background/Objectives: Motor vehicle collision (MVC) cervical acceleration–deceleration (CAD) spine injuries are prevalent, costly, and complicated conditions. CAD injuries, or whiplash-associated disorders (WAD), present with neuromusculoskeletal signs and symptoms. In total, 50% of MVC WAD/CAD injuries result in chronic neck-related disability, of which 30% are moderate-to-severe. Poor recovery is associated with little-to-no recovery after 3 months. This study reports on health outcomes of patients with MVC/CAD injuries treated with Chiropractic BioPhysics^® (CBP^®) spinal rehabilitation beyond little-to-no recovery in neck pain (NP) and disability after 3-to-4 months. Methods: This multicenter retrospective consecutive series reports on patients who met inclusion/exclusion criteria from a records review from two private practices with advanced training in CBP^®. Results: In total, 51 patients (26 males), 18–74 years-of-age (mean age 42.8 ± 3.6 years), presented with post-MVC NP and disability. Pre-treatment radiographs revealed decreased cervical curvature (ARA C2-C7) measuring −10.3 ± 2.0° (ideal is −42.0°) and anterior head translation (Tz C2-C7) measuring 28.5 ± 2.0 mm (ideal is 0 mm). The pre-treatment NP numeric rating scale (NRS) scored 6.0 ± 1.0, and the neck disability index (NDI) scored 54.3 ± 9.3% (severe). Patients were treated using CBP^® for 64.5 ± 4.7 visits over 31.6 ± 3.7 weeks. Post-treatment radiographs revealed an improved ARA C2-C7 to −22.5 ± 2.3° and Tz C2-C7 to 15.9 ± 1.6 mm (p < 0.001). Subsequent 3-to-4-month re-exam showed little-to-no change in NP and disability outcomes. Post-treatment outcomes at a mean 18.5 weeks after the 3-to-4-month re-exam showed significant (p < 0.001) improvements in NP NRS to 1.1 ± 0.7 and NDI to 6.8 ± 5.5 (minimal). Conclusions: CBP^® improves cervical lordosis and posture, which may help improve moderate-to-severe WAD/CAD spine injuries beyond 3-to-4 months of little-to-no recovery. Full article

Background/Objective: Type 2 Diabetes Mellitus (T2DM) represents a major increasing burden for primary care systems worldwide. Digital health interventions (DHIs) have been proposed as scalable tools to improve glycemic control, yet uncertainty remains regarding which intervention characteristics yield the greatest benefit. To evaluate the effectiveness of DHIs on HbA1c levels in adults with T2DM and to examine whether intervention duration, engagement intensity, glucometer integration, and healthcare provider involvement modify glycemic outcomes. Data Sources: PubMed, Embase, Cochrane Library, and JMIR databases were systematically searched for relevant studies published between January 2020 and May 2025. Study Eligibility Criteria: Randomized controlled trials comparing DHIs plus usual care versus usual care alone in adults with T2DM and reporting HbA1c as the primary outcome. Methods: Data were extracted using the Jadad scale and TIDieR framework. Random-effects meta-analysis estimated pooled mean differences (MD) in HbA1c with 95% CIs. Subgroup analyses examined effects by intervention characteristics. Heterogeneity and sources of variance were assessed through Cochran’s Q, I², meta-regression, and sensitivity analyses (leave-one-out and trim-and-fill). Results: Thirteen RCTs (n ≈ 20,000) met inclusion criteria. DHIs achieved significant HbA1c reductions (range 0.01% to 1.57%; pooled MD −1.08%; 95% CI −1.18 to −0.99; p = 0.001). Short-term (≤6 months), low-intensity interventions showed the largest effect sizes (MD −1.16%, 95% CI 0.94 to 1.39). Glucometer integration and healthcare provider involvement contributed minimally to additional benefit. Meta-regression confirmed substantial heterogeneity, but no single factor explained variance across studies. Limitations: Considerable heterogeneity across interventions and variability in engagement measurement may limit the generalizability of findings. Conclusions: Short-term, low-intensity DHIs significantly improve glycemic control in primary care populations with T2DM. Advanced meta-analytic techniques confirm the robustness of these effects, providing practical guidance for selecting and implementing effective digital interventions in routine diabetes care. Full article

Pancreatic β-cell dysfunction is the key driver of type 2 diabetes, and anthocyanins have been proposed as dietary compounds that may help preserve β-cell health. This systematic review aimed to synthesise evidence on the direct effects of anthocyanins on β-cell viability, apoptosis, oxidative stress, and insulin secretion across in vitro models. Four databases were searched in March–April 2025, and eighteen studies met the inclusion criteria. Purified anthocyanins—including cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), malvidin-3-glucoside (M3G), and delphinidin-3-glucoside (D3G)—as well as anthocyanin-rich berry extracts, were tested in INS-1, MIN6, RIN-m5F cells and primary mouse or human islets under glucotoxic, lipotoxic, oxidative, cytokine, and amyloidogenic stress. Anthocyanins consistently improved β-cell viability, reduced apoptosis, and lowered reactive oxygen species (ROS), nitric oxide (NO), and thiobarbituric acid reactive substances (TBARSs) levels while enhancing antioxidant enzyme activities. Multiple studies showed upregulation of insulin secretion-related genes and proteins, and both acute and chronic treatments increased glucose-stimulated insulin secretion under normal and stressed conditions. Mechanistic pathways involved modulation of mitogen-activated protein kinase (MAPK) signalling, endoplasmic reticulum (ER) stress responses, inflammatory mediators, and mitophagy (PINK1/PARKIN). While effective in vitro concentrations were higher than typical circulating levels, the collective evidence highlights anthocyanins as promising β-cell protective agents and underscores the need for studies examining their metabolites and physiologically relevant exposure. Full article

Epithelial-mesenchymal transition (EMT) is a key driver of invasion, metastasis, and treatment resistance in gastric cancer, yet its post-transcriptional regulation by microRNAs (miRNAs) is not fully delineated. We performed a structured literature search in PubMed, Web of Science, and Scopus for studies evaluating miRNAs in relation to EMT in gastric cancer and synthesised tumor-intrinsic, microenvironmental, and circulating EMT-related miRNA networks. Downregulated, predominantly tumor-suppressive miRNAs, including miR-34a, miR-200 family, miR-148a, miR-204, miR-30a, miR-101, miR-218, miR-26a, miR-375, miR-506, and others, converge on EMT transcription factors and pathways such as ZEB1/2, Snail, TGF-β/SMAD, Wnt/β-catenin, c-Met, and PI3K/AKT, and their restoration reverses EMT phenotypes in preclinical models. Upregulated oncomiRs, such as miR-21, miR-17-5p, miR-106b-5p, miR-23a, miR-130a-3p, miR-196a-5p, miR-181a, miR-616-3p, miR-301a-3p, miR-150, miR-27a-3p and miR-192/215, target tumor suppressors and reinforce these pathways. Cancer-associated fibroblast, macrophage, neutrophil, and natural killer cell-derived miRNAs, together with systemic indices such as the neutrophil-to-lymphocyte ratio and mediators like FAM3C, add microenvironmental layers of EMT regulation. Several EMT-related miRNAs show consistent associations with invasion, metastasis, peritoneal dissemination, prognosis, and chemoresistance, and many are detectable in circulation. Overall, EMT-related miRNAs orchestrate gastric cancer cell plasticity and tumor-microenvironment crosstalk and represent promising biomarker and therapeutic candidates that warrant validation in prospective, subtype-stratified, and translational studies. Full article

Zearalenone (ZEA) is a common estrogenic mycotoxin in rabbit breeding that causes various toxic effects. Selenomethionine (SeMet) is a feed additive with potent anti-inflammatory and antioxidant properties. To evaluate the protective role and action mechanism of SeMet against ZEA-induced liver injury, 90-day-old rabbits were randomized into five groups: control, ZEA-alone, and SeMet pretreatment at 0.2, 0.35, and 0.5 mg/kg. SeMet was administered for 21 days, followed by continuous intragastric ZEA (1.2 mg/kg B.W.) for 7 days starting on day 15. As a result, ZEA exposure significantly elevated liver function parameters, disrupted lobular architecture, and impaired glycogen synthesis. It also induced liver oxidative stress, thus upregulating expressions of Bax, Cyt C, Caspase-3, and Caspase-9, triggering hepatocyte apoptosis, mitochondrial damage, and mitophagy. SeMet pretreatment activated SIRT1, reduced the acetylated FOXO1/P53 levels, and enhanced CAT and SOD2 expression, mitigating ZEA-induced oxidative stress, apoptosis, and mitophagy. Based on the above findings, SeMet’s alleviating effect might be mediated via the SIRT1-FOXO1/P53 pathway, with 0.35 mg/kg of SeMet exerting the optimal efficacy, highlighting its therapeutic potential for mitigating ZEA-induced hepatotoxicity in rabbits. Full article

Background: Vancomycin is a critically important antimicrobial in human medicine, and vancomycin-non-susceptible enterococci represent a One Health concern when animal reservoirs contribute to the wider resistance ecology. We aimed to characterize vancomycin non-susceptibility among poultry-derived Enterococcus spp. from Hungary, using a combined phenotypic–genomic approach. Methods: Following a phenotypic pre-screen with antimicrobials authorized for poultry, 218 isolates with elevated minimum inhibitory concentrations (MICs) were selected for extended broth microdilution testing including vancomycin. Vancomycin susceptibility was interpreted using Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints and European Committee on Antimicrobial Susceptibility Testing (EUCAST) epidemiological cut-off values (ECOFFs). Whole-genome sequencing was performed on a targeted multidrug resistant (MDR) subset (n = 42), enriched for elevated or borderline vancomycin MICs and stratified by region and host species (chicken, turkey), and resistance determinants were annotated against the Comprehensive Antibiotic Resistance Database (CARD) using stringent similarity/coverage thresholds. Results: Among the 218 pre-screened isolates (126 from chickens; 92 from turkeys), 196 (89.9%) met MDR criteria. For vancomycin, 15.6% of isolates were resistant and 9.2% intermediate by CLSI, while EUCAST ECOFF classification placed 34.9% in the non-wild-type group. The vancomycin MIC distribution was right shifted, with high-end MICs observed. In the sequenced subset, vancomycin-associated determinants consistent with the vanC pathway (including regulatory and auxiliary components) were detected in five isolates. Beyond vancomycin-related determinants, the WGS subset harbored common resistance genes consistent with the observed multidrug-resistant phenotypes. Conclusions: Vancomycin non-susceptibility was detected among pre-screened poultry-derived Enterococcus isolates in Hungary, and genomic analysis revealed vanC-associated and other peptide antibiotic resistance signatures. These findings support targeted One Health surveillance integrating MIC distributions with genomic resistance determinants in food animal reservoirs. Full article

Sophora tonkinensis is a valuable medicinal plant whose cultivation is constrained by drought and cadmium (Cd) contamination. DNA methylation, mediated by cytosine-5 DNA methyltransferases (C5-MTases) and DNA demethylases (dMTases), contributes to plant stress response; however, these gene families have remained uncharacterized in S. tonkinensis. Here, we identified 12 methylation-related genes (four StC5-MTases and eight StdMTases) and analyzed their phylogeny, duplication, promoter cis-elements, and expression patterns under Cd exposure and drought/rehydration. Most duplicated pairs showed Ka/Ks < 1, consistent with purifying selection. StCMT1 and StMET2 were induced by both Cd and drought stress but declined after rehydration, whereas StROS1b and StROSlike3 responded rapidly to both stresses. Heterologous overexpression in Nicotiana benthamiana improved growth under Cd stress for StCMT1 lines and under PEG-induced osmotic stress for StROSlike3 lines, as reflected by plant height and whole-plant fresh weight. Together, these findings establish a genome-wide resource for DNA methylation machinery in S. tonkinensis and provide candidate genes for investigating epigenetic regulation of abiotic stress adaptation. Full article

Progressive climate change and building morphology influence the specific microclimate of built-up areas. This has a fundamental role in research on energy use and thermal comfort inside buildings. Most studies using data for dynamic energy simulation are based on information collected at meteorological stations in rural areas. This can lead to erroneous predictions. The main goal of the study was to combine two simulation tools—ENVI-met for microclimate predictions around historical building layouts, and DesignBuilder for assessing indoor comfort. Illustrating the impact of input data on simulation results was conducted using three types of weather data: (1) from a field campaign, (2) from a suburban station, and (3) from the typical meteorological year. The obtained results confirm that the highest precision was achieved in analyses where information obtained at a real scale in the city centre was used as boundary conditions (field measurements: MAPE = 0.6 °C, RMSE = 0.7 °C). The next step was to estimate the thermal sensations inside the living room of the existing residential building. Thermal comfort was determined using the operative temperature as an indicator. Incorporating realistic urban weather inputs enhanced the reliability of indoor comfort modelling and provided a more accurate basis for planning thermal resilience in historic residential buildings. Full article

Poorly differentiated gastric carcinoma (PGC) is aggressive, yet subtype-specific genomics are under-characterized. We queried AACR Project GENIE^® (cBioPortal v18.0-public; 12 August 2025) for PGC and analyzed somatic alterations from targeted panels (depth ≥ 100×; variant allele frequency ≥ 5%). Mutation and copy number frequencies were summarized, co-occurrence and exclusivity were tested, and primary versus metastatic tumors were compared using chi-square with Benjamini–Hochberg correction. The cohort included 189 tumors from 188 patients (71% primary; 25% metastatic), with primary and metastatic tumor samples being collected from different patients. Recurrently mutated genes were TP53 (48.7%), CDH1 (31.2%), ARID1A (21.2%), KMT2C (8.5%), and POLD1 (7.4%); additional alterations involved ERBB3, KMT2D, KEL, CDKN2A, and FAT1 (≈1–7%). Amplifications in CCNE1 (8.2%) and FGFR2 (7.6%) were common, alongside gains in MET, MYC, KRAS, and ERBB2 and losses in CDKN2A/CDKN2B, CDH1, and PTEN. Significant co-occurrence was observed for POLD1–KMT2D (p < 0.001), POLD1–ARID1A (p < 0.001), and ARID1A–KMT2D (p < 0.001), while TP53 was mutually exclusive with ARID1A (p = 0.029) and CDH1 (p = 0.041). CDH1 (48.9% vs. 29.6%; p = 0.021) and MLH1 (8.5% vs. 1.5%; p = 0.040) were enriched in metastases, and CCNE1 alterations showed female predominance (p = 2.83 × 10⁻⁴). Several “primary-only” findings likely reflect small denominators and require replication. PGC demonstrates a mutational framework dominated by TP53, CDH1, ARID1A, and recurrent CCNE1/FGFR2 amplifications, underscoring dysregulation of cell cycle and chromatin-remodeling pathways as key drivers. Co-occurrence of POLD1, ARID1A, and KMT2D suggests coordinated disruption of DNA repair and epigenetic regulation, whereas mutual exclusivity of TP53, ARID1A, and CDH1 indicates distinct tumorigenic routes. Metastatic enrichment of CDH1 and MLH1 supports their roles in invasion and therapeutic resistance. Together, these findings highlight candidate biomarkers and actionable pathways warranting validation in larger, multi-omic cohorts to refine precision treatment strategies for this aggressive gastric cancer subtype. Full article

Background: Parthenocissus quinquefolia (Virginia creeper), widely distributed and used in Chile, lacks a systematic characterization of its bioactive components. This study synthesizes the evidence on the phytochemical composition and biological activities of P. quinquefolia, with emphasis on metabolites involved in redox regulation and inflammation. Methods: A systematic review was conducted following PRISMA 2020 guidelines. Searches were performed across four electronic databases, including original studies reporting antioxidant and anti-inflammatory effects. Results: Of 665 records identified, 14 studies met the inclusion criteria. Phytochemical analyses revealed phenolic compounds, particularly flavonoids (e.g., catechin, epicatechin, gallocatechin, epigallocatechin, quercetin, rutin, isoquercitrin, myricetin, luteolin, naringin) and stilbenes (e.g., ε-viniferin, miyabenol C). These metabolites exhibit antioxidant activity through ROS scavenging, metal chelation, and Nrf2/ARE activation. Anti-inflammatory effects were attributed to the downregulation of NF-κB, AP-1, and MAPK signaling, inhibition of NLRP3 inflammasome activation, and suppression of COX-2/iNOS expression. Conclusions: P. quinquefolia is a rich source of phenolic metabolites with robust antioxidant and anti-inflammatory mechanisms. The consistency of molecular responses across studies highlights its potential as a promising candidate for phytotherapeutic development targeting oxidative stress and inflammatory pathways. Full article