Search Results (9,344)

Backgroud: Adjuvant chemotherapy is crucial for the treatment of advanced gastric cancer. However, various factors negatively impact chemoadherence, with malnutrition after gastrectomy being a critical determinant. This study aims to analyze the impact of malnutrition, assessed through the Global Leadership Initiative on Malnutrition (GLIM) and other immunonutritional indices, on chemoadherence and its subsequent effect on survival. Methods: This retrospective study included 116 patients who underwent curative gastrectomy and received oxaliplatin and capecitabine (XELOX). Preoperative nutritional status was assessed using the GLIM criteria along with other immunonutritional indices, such as the prognostic nutritional index (PNI), C-reactive protein-to-albumin ratio (CAR), neutrophil–lymphocyte ratio (NLR), controlling nutritional status (CONUT) score, and modified Glasgow Prognostic Score (mGPS). Chemotherapy adherence was measured using relative dose intensity (RDI). Statistical analyses included least absolute shrinkage and selection operator (LASSO) regression to identify the key predictors of RDI and Cox proportional hazards models and assess the impact on survival. Results: Overall, 116 patients were included in this analysis. In the multivariate analysis using LASSO regression, higher GLIM severity was independently associated with a lower RDI (coefficient = −0.0216; p < 0.01). Other significant factors influencing RDI included older age (p < 0.01), female sex (p = 0.02), higher mGPS (p = 0.03), higher CONUT score (p = 0.04), and higher CAR (p = 0.05), all of which were associated with a lower RDI. The Cox proportional hazards analysis revealed that higher RDI was significantly associated with better survival (hazard ratio [HR] = 0.06; p < 0.005). Conclusions: This study highlights the critical role of immunonutritional status, particularly as measured using the GLIM criteria, in maintaining adherence to chemotherapy and improving survival outcomes in patients with gastric cancer. Routine preoperative nutritional assessments using GLIM can help identify high-risk patients, and early nutritional interventions may improve chemotherapy adherence and outcomes. These findings support the integration of nutritional strategies, specifically targeting those identified by the GLIM, into standard care to enhance the efficacy and survival of chemotherapy. Full article

Background and Objectives: Head and neck squamous cell carcinomas (HNSCCs) vary significantly in terms of invasiveness, growth rate, and metastatic potential. This study aimed to investigate the expression of several prognostic biomarkers (Ki67, p53, EGFR, COX-2, Cx43, and p16) in HNSCC from various anatomical regions and to correlate these expressions with clinicopathological parameters. Materials and Methods: We performed immunohistochemistry on 91 histologically verified HNSCC cases from the County Emergency Hospital, Targu Mures. Biomarker expression for Ki67, COX-2, and Cx43 was assessed using a standard immunoexpression scoring system: S1: 0–10%, S2: 11–25%, S3: 26–50%, S4 > 50%; EGFR was scored based on membrane staining intensity: 0, 1+, 2+, 3+; we classified p16 as positive or negative; p53 was grouped into mutant and wild-type; and we compared these across histopathological types, tumor grades, anatomical locations, gender, and different age groups. We performed a comparative analysis of Cx43 expression levels in relation to the expression of the rest of the markers. Statistical analysis was conducted using GraphPad InStat 3 software, version 3.06 (GraphPad Software Inc., San Diego, USA). Results: The majority of tumors were in males (95.6%) aged 51–60 years. Mutant p53 expression was prevalent in most cases. Elevated Ki67 and EGFR expression were associated with more aggressive tumors. COX-2 levels varied, with a higher proportion of moderate and high immunoexpression (S3 + S4) observed in patients under 70 years old. Cx43 expression was generally low, especially in extralaryngeal tumors. Conclusions: HNSCC primarily affects older males, with the larynx being the most common site. High levels of Ki-67 and EGFR suggest more aggressive tumors, while low COX-2 levels reflect varying prognoses. Women may develop more aggressive tumors, and extralaryngeal tumors often present with more challenging prognoses. Low Cx43 expression may be more likely to coincide with higher Ki67 and COX-2 levels, possibly indicating a link with more aggressive tumor behavior. Full article

Lung inflammation caused by fine particulate matter (PM), particularly PM2.5, poses a significant public health challenge, with oxidative stress and inflammation playing central roles in its pathophysiology. This study evaluates the protective effects of phytosome-encapsulated extract of purple waxy corn tassel (PPT) against PM2.5-induced lung inflammation. Male Wistar rats received PPT at doses of 100, 200, and 400 mg/kg BW for 21 days prior to exposure and continued to receive the same doses for 27 days during PM2.5 exposure. Significant reductions in inflammatory markers, including cyclooxygenase-2 (COX-II), various interleukins (IL-1β, IL-6, IL-8), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB), were observed, indicating that PPT effectively regulates the inflammatory response. Additionally, PPT improved oxidative stress markers by reducing malondialdehyde (MDA) levels and enhancing antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby restoring lung antioxidant defenses. Notably, the study revealed that PPT modulates epigenetic mechanisms, as evidenced by decreased histone deacetylase (HDAC) activity and upregulation of sirtuins in lung tissue. These epigenetic modifications likely contribute to the reduction in inflammation and oxidative stress, suggesting a multifaceted protective role of PPT that involves both direct biochemical pathways and epigenetic regulation. The interplay between reduced inflammatory signaling, enhanced antioxidant capacity, and epigenetic modulation underscores PPT’s potential as a therapeutic agent for managing respiratory inflammation-related diseases and its promise for the development of future functional food products. Full article

Petunidin-3-O-(trans-p-coumaroylrutinoside)-5-O-glucoside (PtCG), the primary anthocyanin ingredient in Lycium ruthenicum Murr., possesses a range of biological activities, including antioxidative properties and melanin inhibition. This study aimed to investigate the protective effect of PtCG on D-galactose (D-gal)-induced aging in female mice and elucidate the underlying molecular pathways. Behavioral experiments, including the MWW and Y-maze tests, revealed that PtCG significantly ameliorated cognitive decline and enhanced learning and memory abilities in aging mice. Regarding biochemical indicators, PtCG considerably improved superoxide dismutase (SOD) and glutathione (GSH) activity while reducing malondialdehyde (MDA) and acetylcholinesterase (AChE) levels in the hippocampus and serum. Furthermore, PtCG ingestion alleviated liver injury by decreasing alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (AKP) levels, and attenuated renal damage by reducing blood urea nitrogen (BUN) and uric acid (UA) levels. Transmission electron microscopy (TEM) results demonstrated that PtCG restored the function and quantity of synapses in the hippocampus. Hematoxylin and eosin (H&E), Masson’s trichrome, and Nissl staining revealed that PtCG significantly improved the relevant pathological characteristics of liver and hippocampal tissues in aging mice. The molecular mechanism investigation showed that PtCG downregulated the protein expression of microglial marker ionized calcium-binding adapter molecule 1 (Iba1), astrocytic marker glial fibrillary acidic protein (GFAP), β-secretase 1 (BACE-1), and amyloid-beta_1–42 (Aβ_1–42) in the hippocampus of aging mice. The protein expression of inflammatory pathway components, including nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), and interleukin-1 beta (IL-1β), was also suppressed. These findings suggest that PtCG may possess anti-aging properties, with its mechanism of action potentially linked to the attenuation of neuroinflammation, oxidative stress, and liver and kidney damage. PtCG may have future applications as a functional food for the treatment of aging-related disorders. Full article

Pyrimidine derivatives exhibit a wide range of biological activities, including anti-inflammatory properties. The aim of this study was to investigate the effects of tested pyrimidine derivatives on the activity of cyclooxygenase isoenzymes (COX-1 and COX-2), antioxidant properties, and their ability to inhibit the growth of inflammatory cells. In vitro tests were conducted to assess the ability of pyrimidine derivatives L1–L4 to inhibit COX-1 and COX-2 activity using the TMPD oxidation assay (N,N,N',N'-tetramethyl-p-phenylenediamine). The compounds’ ability to inhibit the growth of lipopolysaccharide (LPS)-stimulated THP-1 (human leukemia monocytic) monocyte cells and their impact on reactive oxygen species (ROS) levels in an inflammatory model were also evaluated. The binding properties of human serum albumin (HSA) were assessed using UV–Vis spectroscopy, circular dichroism (CD), and isothermal titration calorimetry (ITC). Among the tested pyrimidine derivatives, L1 and L2 showed high selectivity towards COX-2, outperforming piroxicam and achieving results comparable to meloxicam. In the sulforhodamine B (SRB) assay, L1 and L2 demonstrated dose-dependent inhibition of LPS-stimulated THP-1 cell growth. Additionally, ROS assays indicated that these compounds reduced free radical levels, confirming their antioxidant properties. Binding studies with albumin revealed that L1 and L2 formed stable complexes with HSA. These results suggest that these compounds could serve as a basis for further research into anti-inflammatory and anticancer drugs with reduced toxicity. Full article

Background: Prostate cancer is the fourth most common cancer and eighth leading cause of cancer-related mortality worldwide. Its incidence is increasing in South Korea. This study aimed to investigate a predictive model for the 5-year survival probability of prostate cancer patients in a Korean primary care setting. Method: This retrospective study used data from the nationwide insurance claims database. The main outcome was survival probability 5 years after the initial diagnosis of prostate cancer. Potential confounding factors such as age, body mass index (BMI), blood pressure, laboratory results, lifestyle behaviors, household income, and comorbidity index were considered. These variables were available in the national health check-up information. A Cox proportional hazards regression model was used to develop the predictive model. The predictive performance was calculated based on the mean area under the receiver operating characteristic curve (AUC) after 10-fold cross-validation. Results: The mean 5-year survival probability was 82.0%. Age, fasting glucose and gamma-glutamyl transferase levels, current smoking, and multiple comorbidities were positively associated with mortality, whereas BMI, alkaline phosphatase levels, total cholesterol levels, alcohol intake, physical activity, and household income were inversely associated with mortality. The mean AUC after 10-fold cross-validation was 0.71. Conclusions: The 5-year survival probability model showed a moderately good predictive performance. This may be useful in predicting the survival probability of prostate cancer patients in primary care settings. When interpreting these results, potential limitations, such as selection or healthy user biases, should be considered. Full article

In this study, we investigated the protective effects of astaxanthin (AST) against oxidative stress induced by the combination of azoxymethane (AOM) and dextran sulfate sodium (DSS) in colitis-associated cancer (CAC) and TNF-α-induced human colorectal cancer cells (SW480), as well as the underlying mechanism. In vitro experiments revealed that astaxanthin reduced reactive oxygen species (ROS) generation and inhibited the expression of Phosphorylated JNK (P-JNK), Phosphorylated ERK (P-ERK), Phosphorylated p65 (P-p65), and the NF-κB downstream protein cyclooxygenase-2 (COX-2). In vivo experiments showed that astaxanthin ameliorated AOM/DSS-induced weight loss, shortened the colon length, and caused histomorphological changes. In addition, astaxanthin suppressed cellular inflammation by modulating the MAPK and NF-κB pathways and inhibiting the expression of the proinflammatory cytokines IL-6, IL-1β, and TNF-α. In conclusion, astaxanthin attenuates cellular inflammation and CAC through its antioxidant effects. Full article

Background/Objectives: This study investigates the prevalence and prognostic impact of concomitant anemia in unselected patients undergoing invasive coronary angiography (CA). The spectrum of patients undergoing CA has significantly changed during the past decades, related to ongoing demographic changes and improved treatment strategies for patients with cardiovascular disease. Methods: Consecutive patients undergoing invasive CA from 2016 to 2022 were retrospectively included at one institution. Patients with anemia (i.e., hemoglobin < 13.0 g/dL for males and <12.0 g/dL for females) were compared with patients without anemia (i.e., nonanemics). The primary endpoint was rehospitalization for heart failure (HF) at 36 months. Secondary endpoints comprised the risk of rehospitalization for acute myocardial infarction (AMI) and coronary revascularization. Statistical analyses included Kaplan–Meier, multivariable Cox proportional regression analyses, and propensity score matching. Results: From 2016 to 2022, 7645 patients undergoing CA were included with a median hemoglobin level of 13.2 g/dL. Anemics had a higher prevalence of coronary artery disease (CAD) (76.3% vs. 74.8%; p = 0.001), alongside an increased need for percutaneous coronary intervention (PCI) (45.3% vs. 41.5%; p = 0.001). At 36 months, the risk of rehospitalization for HF was higher in anemic patients (27.4% vs. 18.4%; p = 0.001; HR = 1.583; 95% CI 1.432–1.750; p = 0.001), which was still evident after multivariable adjustment (HR = 1.164; 95% CI 1.039–1.304; p = 0.009) and propensity score matching (HR = 1.137; 95% CI 1.006–1.286; p = 0.040). However, neither the risk of AMI (8.4% vs. 7.4%, p = 0.091) nor the risk of coronary revascularization at 36 months (8.0% vs. 8.5%, p = 0.447) was higher in anemic compared with nonanemic patients. Conclusions: In consecutive patients undergoing CA, concomitant anemia was independently associated with an increased risk of rehospitalization for HF, but not AMI or coronary revascularization. Patients with LVEF ≥ 35% and multivessel disease were especially susceptible to anemia-induced HF-related rehospitalization. Full article

Previous studies have focused on the impact of individual factors on lane departure warning (LDW) utility during driving. However, comprehensive analysis has not been considered based on multiple variables, such as driver characteristics. This paper aims to propose a methodology in exploring the utility of LDW under varied warning timing situations, focusing on changes in driving style and distraction level to obtain the optimal warning timing matching relationship. A driving simulator experiment with a mixed 4 × 3 factor design was conducted. The design matrix includes four level of secondary task (ST) conditions and three warning timings situations for drivers with various driving styles. To estimate the utility of the LDW system, lane departure duration (LDD) was selected as a time-based measure of utility. Both the Kaplan-Meier method and COX model were applied and compared. Combined with questionnaire results, the results indicate that both driving style and distraction state are significant influence factors. Generally, the results suggest that the more aggressive drivers lead to the more severe lane departure behavior and they preferred late warning. In terms of distraction state, the LDD increases with the level of ST remarkably. This implies that the earlier warning timing should be given for the higher-level distraction state condition. It was also observed that adaptive warning timing is needed based on the analysis of the interactive effect among multiple variables. The results provide empirical data for the optimization of LDW system design. Full article

Background/Objectives: The relationship between pathologic findings in soft tissue sarcoma (STS) after neoadjuvant treatment and oncological outcomes remains uncertain due to varying evaluation methods and cut-off values. This study aims to assess pathologic findings after neoadjuvant radiotherapy in STS using the EORTC-STBSG response score and evaluate its prognostic value. Methods: Clinical and outcome data from 44 patients were reviewed. Resected specimens were re-evaluated to measure viable cells, necrosis, fibrosis, and hyalinization. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan–Meier survival analysis. Cox proportional hazards regression was used for univariate and multivariate analyses to correlate outcomes with pathologic response. Results: The median percentages of viable cells, necrosis, and fibrosis/hyalinization were 20%, 11%, and 40%, respectively. A pathologic complete response (pCR), defined as ≤5% viable cells, was achieved in 25% of cases. Local recurrence occurred in 33% of cases, with a significantly higher rate of 64% after R1 resection compared to 22% after R0 resection. Distant metastases were observed in 42% of patients, primarily in the lungs. The 3-year rates for LRFS, DMFS, and OS were 65%, 54%, and 67%, respectively. A correlation between outcomes and tumor size, grade and histological subtype was observed. Classifying pathologic response by the EORTC-STBSG score failed to show an association with outcomes. Patients achieving pCR showed lower risk of LR and improved OS. Conclusions: While the EORTC-STBSG score did not show a prognostic value, resection specimens with ≤5% viable cells were linked to improved LRFS and OS. Full article

Background and Objectives: Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. Materials and Methods: A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan–Meier survival analysis and Cox regression models were used to identify significant prognostic factors. Results: The Kaplan–Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. Conclusions: The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies. Full article

Lipoxygenases (LOXs) from lower organisms have substrate flexibility and function versatility in fatty acid oxidation, but it is not clear how these LOXs acquired the ability to execute multiple functions within only one catalytic domain. This work studied a multifunctional LOX from red alga Pyropia haitanensis (PhLOX) which combined hydroperoxidelyase (HPL) and allene oxide synthase (AOS) activity in its active pocket. Molecular docking and site-directed mutagenesis revealed that Phe642 and Phe826 jointly regulated the double peroxidation of fatty acid, Gln777 and Asn575 were essential to the AOS function, and the HPL activity was improved when Asn575, Gln777, or Phe826 was replaced by leucine. Phylogenetic analysis indicated that Asn575 and Phe826 were unique amino acid sites in the separated clades clustered with PhLOX, whereas Phe642 and Gln777 were conserved in plant or animal LOXs. The N-terminal START/RHO_alpha_C/PITP/Bet_v1/CoxG/CalC (SRPBCC) domain of PhLOX was another key variable, as the absence of this domain disrupted the versatility of PhLOX. Moreover, the functions of two homologous LOXs from marine bacterium Shewanella violacea and red alga Chondrus crispus were examined. The HPL activity of PhLOX appeared to be inherited from a common ancestor, and the AOS function was likely acquired through mutations in some key residues in the active pocket. Taken together, our results suggested that some LOXs from red algae attained their versatility by amalgamating functional domains of ancestral origin and unique amino acid mutations. Full article

The species of Purpureocillium are cosmopolitan and multitrophic fungi that can infect a wide range of invertebrate hosts. This study reports the mitogenome of P. atypicola, a specialized spider pathogenic fungus. The 112,465 bp mitogenome encoded genes typically found in fungal mitogenomes, and a total of 52 introns inserted into seven genes. A comparison with three other Purpureocillium species revealed significant differences in length and intron number, primarily due to intron variation; however, there was no dynamic variation in the introns of the cox1 gene within the same species of the Purpureocillium genus. Different mitochondrial protein-coding genes showed variable degrees of genetic differentiation among these species, but they were all under purifying selection. Additionally, frequent intron loss or gain events were detected to have occurred during the evolution of the Ophiocordycipitaceae mitogenomes, yet the gene arrangement remains conserved. A phylogenetic analysis of the combined mitochondrial gene set gave identical and well-supported tree topologies. The estimated age of the crown of Ophiocordycipitaceae and Purpureocillium were around the Early Cretaceous period (127 Mya) and Late Cretaceous period (83 Mya), respectively. The results of this study advance our understanding of the genomics, evolution, and taxonomy of this important fungal group. Full article

Background: Refeeding syndrome (RFS) is a potentially life-threatening condition that can occur in preterm infants if nutritional support is initiated or increased after a period of starvation or malnutrition. Objectives: The current study aimed to examine the short-term clinical outcomes of RFS in preterm infants born at ≤32 weeks of gestation. Methods: Infants with a gestational age of ≤32 weeks and a birth weight of <1500 g who were born and admitted to the level III neonatal intensive care unit and received parenteral nutrition upon admission were retrospectively evaluated. The modified log Poisson regression with generalized linear models and a robust variance estimator was applied to adjust the outcomes of infants. Results: In total, 760 infants met this study’s inclusion criteria. Of them, 289 (38%) developed RFS. RFS was significantly associated with a composite outcome of mortality and intraventricular hemorrhage. Based on the multivariate Cox regression analysis adjusted for significant potential confounders, RFS was significantly associated with increased mortality risk, with a hazard ratio for death in infants with RFS being 1.74-fold higher compared to those without RFS. Conclusions: Preterm infants born at ≤32 weeks of gestation who develop RFS within the first week of life are at increased risk for both intraventricular hemorrhage and mortality. This study underscores the need for standardized clinical approaches for managing RFS in the neonatal intensive care unit to improve outcomes. Future research should establish a unified RFS definition and conduct clinical trials to optimize parenteral nutrition strategies for this vulnerable population. Full article

(1) Background: Comprehensive and timely lung cancer (LC) staging is essential for prognosis and management. The Lung Diagnostic Assessment Program (LDAP) in Southeastern (SE) Ontario aims to provide rapid, guideline-concordant care for suspected LC patients. We evaluated factors affecting the completeness and timeliness of staging for stage I–III LC patients in SE Ontario, including the impact of LDAP management. (2) Methods: This was a population-based retrospective cohort study using the LDAP database (January 2017–December 2019), linked with the Ontario Cancer Registry, to identify newly diagnosed LC patients. A Cox model approach identified variables associated with staging completeness and timeliness. (3) Results: Among 755 patients, 459 (60.8%) were managed through LDAP. Optimal staging was achieved in 596 patients (78.9%), 23 (3.0%) had alternative staging, and 136 (18.0%) had incomplete staging. In the adjusted analyses, LDAP management was associated with a higher likelihood of complete staging (OR 2.29, p < 0.0001) and faster staging completion (β = −18.53, p < 0.0001). Increased distance to PET centres was associated with a longer time to complete staging (β = 8.95 per 100 km, p = 0.0007), as was longer time to diagnosis (β = 21.63 per 30 days, p < 0.0001). (4) Conclusions: LDAP management in SE Ontario significantly improved staging completeness and shortened staging time for stage I–III LC patients. Full article