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Exploring the Cytotoxic Activity of Dillenia serrata Thunb. Leaf Extracts: An In Vitro and In Silico Investigation

Asian Pac J Cancer Prev. 2025 Mar 1;26(3):1043-1051. doi: 10.31557/APJCP.2025.26.3.1043.

ABSTRACT

OBJECTIVE: Dillenia serrata Thunb. an endemic plant from Sulawesi Island, has been used by the local community as medicine for some diseases. However, studies related to these plants are still limited to several diseases. This study intends to investigate the cytotoxic activity of Dillenia serrata Thunb. leaves extract as an anticancer.

METHODS: This study was preceded by gradual maceration and then subjected to phytochemical test to evaluate the contain of secondary metabolites such as alkaloid, flavonoid, tannin, steroid, terpenoid, and saponin, toxicity assay by BSLT method, cytotoxicity test against HeLa cell lines, further compound identification using GC-MS analysis and in silico analysis.

RESULTS: The phytochemical tests demonstrated the presence of tannins, steroids, alkaloids, flavonoids, and saponins. The toxicity test indicated that all three extracts were toxic for Artemia salina L. as the premier test before the cytotoxicity test using HeLa cell lines. The LC50 values for the n-hexane, ethyl acetate, and methanol extracts were 58.27±6.15, 11.06±1.70, and 9.30±1.13 μg/mL, respectively. After evaluating the extracts’ cytotoxicity activity, the ethyl acetate extract has the strongest activity with 91.08±0.23 μg/mL, then this extract was further identified using GC-MS analysis and reveals 51 chemicals which is Phytol as the main components in the extract with %area about 25.64%. Molecular docking analysis of Phytol against Epidermal Growth Factor Receptor (EGFR) showed a good binding energy of around -5.08 kcal/mol. The molecular dynamics simulation supports this result.

CONCLUSION: All extracts demonstrated intense toxicity levels. Out of all the extracts, ethyl acetate extract exhibited the strongest cytotoxic properties to HeLa cell lines with IC50 value 91.08±0.23 μg/mL. Ethyl acetate extract of D. serrata T. contains Phytol compounds which have a quite good affinity to the EGFR. According to this study, ethyl acetate extract has the potential to be used as an alternative to anticancer medication.

PMID:40156423 | DOI:10.31557/APJCP.2025.26.3.1043

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EMMPRIN Correlated with β-CATENIN in Various t Stages of Colorectal Adenocarcinoma

Asian Pac J Cancer Prev. 2025 Mar 1;26(3):1001-1007. doi: 10.31557/APJCP.2025.26.3.1001.

ABSTRACT

OBJECTIVE: Colorectal cancer is the third malignant tumor and the second cause of death in the world. There are several prognostic factors in colorectal adenocarcinoma, one of which is the TNM stage. The T stage is determined based on the depth of tumor invasion. Various proteins can be involved in the invasion process. EMMPRIN is expressed and functions on the surface of cancerous cells. as a mediator of tumor cell invasion. Increased β-Catenin accelerates the process of tumor cell proliferation, migration, and invasion. We aimed to analyze the correlation between EMMPRIN and β-Catenin expression in the T stages of colorectal adenocarcinoma.

METHODS: An observational analytic study was conducted using a cross-sectional approach on 47 paraffin blocks of colorectal adenocarcinoma at the Anatomic Pathology Laboratory of Dr. Soetomo Hospital Surabaya from January 2018 to December 2022. An immunohistochemical examination was performed using EMMPRIN and β-Catenin antibodies, and then the expression of both antibodies will be analyzed using statistical tests.

RESULT: There was a significant correlation between the expression of β-Catenin with various T stages of colorectal adenocarcinoma (p-value 0.0201). There was a significant correlation between the expression of EMMPRIN and β-Catenin in various T-stages of colorectal adenocarcinoma (p-value: 0.0209).

CONCLUSION: There is a positive correlation between EMMPRIN and β-Catenin expression and various T-stages of colorectal adenocarcinoma with weak strength. The existence of EMMPRIN and β-Catenin stimulates colorectal cancer cells to continue invasion.

PMID:40156418 | DOI:10.31557/APJCP.2025.26.3.1001

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Comparison Between Breath-Hold and the Inspiratory Phase of Free Breathing in Left Breast Cancer Radiotherapy: Target Volume Coverage and Organ Sparing

Asian Pac J Cancer Prev. 2025 Mar 1;26(3):969-975. doi: 10.31557/APJCP.2025.26.3.969.

ABSTRACT

BACKGROUND: Cardiac mortality and coronary events associated with left breast radiotherapy are correlated with the mean radiation dose to the heart.

METHODS: This prospective phase II study included left breast cancer patients receiving adjuvant locoregional radiotherapy with intensity-modulated radiation therapy (IMRT) following surgery. Patients were treated using the respiratory gating (RPM) technique (Varian Medical Systems, USA). Dosimetric outcomes were compared between deep inspiration breath-hold (DIBH) and the inspiratory phase of free breathing (FB) in the same patients, focusing on target volume coverage and sparing of critical organs (lungs, heart, and coronary arteries). The prescribed dose was 50 Gy in 25 fractions over five weeks to the chest wall or breast and/or lymph nodes, with an additional boost of 10 Gy in five fractions over one week to the tumor bed in breast-conserving surgery (BCS) cases. Two treatment plans were generated per patient: one for DIBH and another for the inspiratory phase of FB.

RESULTS: Between February 2020 and August 2022, 60 patients with a mean age of 50 years were enrolled in the study. The dosimetric analysis showed that the mean heart dose was lower in the DIBH group (4.8 Gy) compared to the FB group (6.4 Gy) with a statistically significant difference (p < 0.0001). Similarly, the mean dose to the left anterior descending artery (LAD) was significantly reduced in DIBH (14 Gy) compared to FB (20.5 Gy) (p < 0.0001). Regarding target volume coverage, the mean planning target volume (PTV) V95% was slightly higher in DIBH (97.3%) than in FB (96.5%) (p = 0.0062). The mean left lung V20 was comparable between the two techniques, with values of 14.4% in DIBH and 14.35% in FB (p = 0.85), indicating no significant difference in lung dose sparing. However, the mean left ventricular dose was significantly lower in DIBH (6 Gy) compared to FB (8.1 Gy) (p < 0.0001), further supporting the advantage of DIBH in reducing cardiac radiation exposure.

CONCLUSION: DIBH plans demonstrated superior target coverage and significantly improved cardiac and coronary sparing compared to FB inspiratory phase plans. However, FB plans remained within acceptable dose constraints. No significant differences were observed in lung dose sparing or beam-on time.

PMID:40156414 | DOI:10.31557/APJCP.2025.26.3.969

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Demographic and social determinants of the interval from symptom onset to diagnosis of pediatric brain tumors: a study of the Connecticut Tumor Registry

J Neurosurg Pediatr. 2025 Mar 28:1-9. doi: 10.3171/2024.12.PEDS24394. Online ahead of print.

ABSTRACT

OBJECTIVE: Pediatric patients frequently experience long intervals between the initial onset of symptoms and the diagnosis of a brain tumor. Understanding the determinants of the prediagnostic symptomatic interval (PSI) has the potential to facilitate earlier initiation of treatment. Here, the authors studied the impact of demographic factors and social determinants of health on the PSI among pediatric brain tumor patients.

METHODS: All pediatric patients with brain tumors included in the Connecticut Department of Public Health’s Tumor Registry from 2004 to 2018 were reviewed. Demographic, clinical, and outcomes data were collected. The primary outcome was the log transformation of the PSI (ln(PSI)), which was modeled as a continuous variable. Statistical analyses included multiple linear regression models with stepwise variable selection. The Akaike Information Criterion (AIC) was used to indicate model fit, and bootstrapping was performed to validate the findings.

RESULTS: Overall, 153 patients met the inclusion criteria with a median (IQR) PSI of 30 (14-60) days. Of the tumors, 91 (59.5%) were classified as malignant and 62 (40.5%) as benign. The multivariable linear regression analysis of ln(PSI) demonstrated that longer PSI was positively associated with older age (β = 0.06, p = 0.004) and was negatively associated with Black or African American race (β = -0.64, p = 0.023), the presence of hydrocephalus on presentation (β = -0.79, p = 0.011), fatigue (β = -0.61, p = 0.047) or hemiparesis (β = -0.82, p = 0.041) as presenting symptoms, and malignant tumor behavior (β = -0.45, p = 0.042). The multiple linear regression model was statistically significant overall (F(7,145) = 5.42, p < 0.001), explaining approximately 21% of the variance ln(PSI), and bootstrapping with 1000 resamples confirmed the reliability of the regression analysis.

CONCLUSIONS: Demographic factors, patterns of presentation, and tumor biology play a role in the interval between symptom onset and the diagnosis of pediatric brain tumors, with potential implications for quality of care and survival. Although this study did not identify a significant association between nondemographic social determinants of health and the PSI, additional studies are needed with more granular measures of economic stability, healthcare access and quality, education access and quality, neighborhood and built environment, and social and community context. Future efforts should target patient populations at increased risk of a prolonged PSI.

PMID:40153845 | DOI:10.3171/2024.12.PEDS24394

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Cost and operating room time savings with single-position prone lateral lumbar interbody circumferential fusion

J Neurosurg Spine. 2025 Mar 28:1-7. doi: 10.3171/2024.11.SPINE23706. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to determine efficiencies associated with dual-position versus single-position lateral lumbar interbody fusion (LLIF).

METHODS: Billing databases were queried for LLIF procedures performed by a single surgeon at a high-volume tertiary care center. Case-specific costs for each procedure were collected. Cases were matched by the number of levels treated. One-level and 2-level LLIFs with percutaneous pedicle screw (PPS) fixation (LLIF+PPS) using a single vendor system were included. Length of stay, operative time, and operative costs were compared for dual-position and single-position LLIF cases using continuous and categorical variable comparisons.

RESULTS: Among 9 patients with 1-level LLIF+PPS, dual-position LLIF+PPS (n = 3) compared with single-position LLIF+PPS (n = 6) was associated with similar mean lengths of stay (2.0 vs 2.2 days), longer operating room time (160.1 vs 149.7 minutes), and greater mean costs for operating room staff and supplies ($1347 vs $1263); however, the differences were not statistically significant. Time-based anesthesiology costs were higher for dual-position LLIF+PPS than for single-position LLIF+PPS ($741 vs $521, p = 0.03). Among 8 patients with 2-level LLIF+PPS, patients undergoing dual-position (n = 5) and single-position (n = 3) LLIF+PPS had similar mean lengths of stay (1.2 vs 1.5 days). However, dual-position surgery was associated with a longer mean operating room time (257.8 vs 182.3 minutes, p = 0.03), greater mean operating room cost ($2275 vs $1352, p = 0.02), and greater time-based cost of anesthesiology coverage ($864 vs $644, p = 0.01).

CONCLUSIONS: In this cohort of patients undergoing 1- and 2-level LLIF+PPS, single-position surgery was associated with shorter operating room time, lower operating room costs, and similar postoperative hospital length of stay when compared with dual-position surgery for a similar pathology.

PMID:40153840 | DOI:10.3171/2024.11.SPINE23706

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Nucleolin as a Potent Biomarker for Predicting Tumor Recurrence among Patients with Hepatocellular Carcinoma after Transplantation

J Gastrointestin Liver Dis. 2025 Mar 28;34(1):81-89. doi: 10.15403/jgld-5873.

ABSTRACT

BACKGROUND AND AIMS: Tumor recurrence poses a significant challenge post-liver transplantation (LT) for hepatocellular carcinoma (HCC), necessitating the development of more precise predictive tools. In this study we aimed to investigate nucleolin as a biomarker for predicting HCC recurrence after LT.

METHODS: A cohort of 241 HCC patients undergoing LT was enrolled from three medical facilities spanning January 1, 2015, to December 31, 2017. Utilizing tissue microarrays, we assessed the predictive potential of nucleolin. Survival analyses, including Kaplan-Meier and log-rank tests, were employed to scrutinize overall survival and recurrence-free survival. Based on univariate and multivariate Cox regression analyses of preoperative parameters, nomogram and risk score were designed to predict HCC recurrence and determine the effectiveness of the model.

RESULTS: The expression of nucleolin in HCC nucleus was increased. High nucleolin expression in tumor tissues correlated with poor overall survival and recurrence-free survival (5-year overall survival ratios: 34% vs. 64.8%, 5-year recurrence-free survival ratios: 36.1% vs.67.9%, all p<0.001). Multivariate Cox regression analysis identified nucleolin expression score, Hangzhou criteria, HBsAg, tumor differentiation and alpha-fetoprotein level as independent risk factors for tumor recurrence in HCC patients post- LT. A new nomogram is established based on the above risk factors with effective prediction efficiency (area under time-dependent receiver operating characteristic =0.742, concordance-index =0.7742).

CONCLUSIONS: Nucleolin can be combined with a nomogram as an effective tool to predict recurrence in HCC patients following LT.

PMID:40153827 | DOI:10.15403/jgld-5873

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Comparison of Effectiveness Between Protein and BCAA in Late Evening Snack on Vietnamese Liver Cirrhotic Outpatients: a Randomized Clinical Trial

J Gastrointestin Liver Dis. 2025 Mar 27;34(1):64-70. doi: 10.15403/jgld-5926.

ABSTRACT

BACKGROUND AND AIMS: Late-evening snacks bring multiple benefits to liver cirrhosis patients. However, a consensus on the nutrient composition of the snack is still not clear. This study showed a direct comparison between a protein snack and a a branched-chained amino acid (BCAA) snack.

METHODS: A randomized clinical trial with 32 Vietnamese liver cirrhosis outpatients (61.0, 57-63 years), allocated into two groups: Protein group (n=16) and BCAA group (n=16) took place. Both groups received a snack providing 270-300 kcal, 50g carbohydrates, <5g lipid, and 13g of protein with 8g being protein powder in Protein group and 4g protein powder and 4g BCAA powder in BCAA group. Serum biochemical parameters, anthropometric data, and Chronic Liver Disease Questionnaire scores were examined in both groups before and after the 3-week intervention.

RESULTS: After receiving the snacks for 3 weeks, albumin was significantly increased in the Protein group (p<0.01) while it was not in the BCAA group. Only the ALT liver enzyme was statistically decreased in the Protein group (p<0.01). After the intervention, the handgrip strength of the Protein group increased from 24.3kg (±9.1 SD) to 25.7kg (±9.2 SD) (p=0.012); while, in BCAA group, the mean also changed from 24.7kg (±6.6 SD) to 25.6kg (±7.4 SD) (p=0.237). The overall Chronic Liver Disease Questionnaire score was significantly increased from 6.0 to 6.7 and 6.6 in the Protein group and the BCAA group, respectively.

CONCLUSIONS: A protein snack is an effective dietary intervention in improving albumin, biochemical parameters, and nutritional status for compensated liver cirrhosis outpatients. Considering cost, availability, and taste, a BCAA snack might be unnecessary for liver cirrhosis outpatients.

PMID:40153825 | DOI:10.15403/jgld-5926

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Effect of Vegan Diet During Greek-Orthodox Religious Fasting on Symptoms of Disorders of Gut-Brain Interaction

J Gastrointestin Liver Dis. 2025 Mar 27;34(1):40-46. doi: 10.15403/jgld-6082.

ABSTRACT

BACKGROUND AND AIMS: Religious fasting observed in diverse populations may influence the reporting of digestive symptoms. Greek-Orthodox (Byzantine style) religious fasting is prolonged and similar to a vegan diet. We aimed to evaluate the association between functional gastrointestinal symptoms and disorders of gut-brain interaction (DGBI) with this religious fasting.

METHODS: We investigated Romanian participants in the Rome Foundation Global Epidemiology Study who observe Greek-Orthodox religious fasting, by adding specific questions on religious fasting to the study questionnaire. Data were analyzed in connection with the reported gastrointestinal symptoms.

RESULTS: 2015 Romanians were included in the analyses. Overall, 716 (35.5%) of the respondents practiced some fasting, of which 446 (62.3%) fasted on Easter and Christmas, 90 (12.6%) observed all fasts, and 625 (87.3%) practiced weekly fasting. Of the latter, 167 (23.3%) fasted every week and 90 (12.6%) reported symptoms during fasting. There were no statistically significant associations between Greek-Orthodox fasting, to any degree, with upper or lower DGBI or gastrointestinal symptoms.

CONCLUSIONS: The results from this representative sample show that a substantial proportion of the Romanian population adheres to Greek-Orthodox fasting. However, in contrast to the a priori hypothesis, we did not have sufficient evidence that religious fasting is associated with the prevalence of DGBI, or with functional gastrointestinal symptoms.

PMID:40153820 | DOI:10.15403/jgld-6082

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Constipation and Risk of Acute Myocardial Infarction: A Systematic Review and Meta-Analysis of Cohort Studies

J Gastrointestin Liver Dis. 2025 Mar 28;34(1):108-114. doi: 10.15403/jgld-5852.

ABSTRACT

BACKGROUND AND AIMS: Constipation is commonly seen among patients with cardiovascular diseases and is linked to adverse outcomes. However, the association between constipation and the risk of acute myocardial infarction (AMI) remains conflicting. Therefore, we aimed to conduct a systematic review and meta-analysis to summarize the available data on this topic.

METHOD: We identified potentially eligible studies from the MEDLINE and EMBASE databases, searching from inception to May 2024, to investigate the association between constipation and the risk of developing AMI. To be included, studies needed to compare incidence of AMI between cohorts with and without constipation. Effect size and 95% confidence intervals (CIs) were combined using the generic inverse variance method. All statistical analyses were performed by Review Manager 5.4.

RESULTS: Our meta-analysis included seven studies that met the eligibility criteria. There were 5,351,976 participants, with a mean age of 57.8 years and 74% were males. We found that patients with constipation had a 14% increased risk of AMI with a pooled risk ratio (RR) of 1.14 (95%CI: 1.08-1.14; I²=85%; p<0.001) compared to those without constipation.

CONCLUSIONS: Our study revealed that constipation is associated with a higher risk of AMI. Emphasizing and addressing gastrointestinal health, including constipation, as an important issue is essential for comprehensive cardiovascular care.

PMID:40153815 | DOI:10.15403/jgld-5852

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Factors Influencing Health Care Technology Acceptance in Older Adults Based on the Technology Acceptance Model and the Unified Theory of Acceptance and Use of Technology: Meta-Analysis

J Med Internet Res. 2025 Mar 28;27:e65269. doi: 10.2196/65269.

ABSTRACT

BACKGROUND: The technology acceptance model (TAM) and the unified theory of acceptance and use of technology (UTAUT) are widely used to examine health care technology acceptance among older adults. However, existing literature exhibits considerable heterogeneity, making it difficult to determine consistent predictors of acceptance and behavior.

OBJECTIVE: We aimed to (1) determine the influence of perceived usefulness (PU), perceived ease of use (PEOU), and social influence (SI) on the behavioral intention (BI) to use health care technology among older adults and (2) assess the moderating effects of age, gender, geographic region, type of health care technology, and presence of visual demonstrations.

METHODS: A systematic search was conducted across Google Scholar, Web of Science, Scopus, IEEE Xplore, and ProQuest databases on March 15, 2024, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Of the 1167 initially identified studies, 41 studies (11,574 participants; mean age 67.58, SD 4.76 years; and female:male ratio=2.00) met the inclusion criteria. The studies comprised 12 mobile health, 12 online or telemedicine, 9 wearable, and 8 home or institution hardware investigations, with 23 studies from Asia, 7 from Europe, 7 from African-Islamic regions, and 4 from the United States. Studies were eligible if they used the TAM or UTAUT, examined health care technology adoption among older adults, and reported zero-order correlations. Two independent reviewers screened studies, extracted data, and assessed methodological quality using the Newcastle-Ottawa Scale, evaluating selection, comparability, and outcome assessment with 34% (14/41) of studies rated as good quality and 66% (27/41) as satisfactory.

RESULTS: Random-effects meta-analysis revealed significant positive correlations for PU-BI (r=0.607, 95% CI 0.543-0.665; P<.001), PEOU-BI (r=0.525, 95% CI 0.462-0.583; P<.001), and SI-BI (r=0.551, 95% CI 0.468-0.624; P<.001). High heterogeneity was observed across studies (I²=95.9%, 93.6%, and 95.3% for PU-BI, PEOU-BI, and SI-BI, respectively). Moderator analyses revealed significant differences based on geographic region for PEOU-BI (Q=8.27; P=.04), with strongest effects in Europe (r=0.628) and weakest in African-Islamic regions (r=0.480). Technology type significantly moderated PU-BI (Q=8.08; P=.04) and SI-BI (Q=14.75; P=.002), with home or institutional hardware showing the strongest effects (PU-BI: r=0.736; SI-BI: r=0.690). Visual demonstrations significantly enhanced PU-BI (r=0.706 vs r=0.554; Q=4.24; P=.04) and SI-BI relationships (r=0.670 vs r=0.492; Q=4.38; P=.04). Age and gender showed no significant moderating effects.

CONCLUSIONS: The findings indicate that PU, PEOU, and SI significantly impact the acceptance of health care technology among older adults, with heterogeneity influenced by geographic region, type of technology, and presence of visual demonstrations. This suggests that tailored strategies for different types of technology and the use of visual demonstrations are important for enhancing adoption rates. Limitations include varying definitions of older adults across studies and the use of correlation coefficients rather than controlled effect sizes. Results should therefore be interpreted within specific contexts and populations.

PMID:40153796 | DOI:10.2196/65269