Background Apigenin, a flavonoid predominantly found in citrus fruits, particularly grapefruit, has attracted significant attention in ethnopharmacology for its diverse therapeutic properties. Method This systematic review focuses on the potential therapeutic impact of Apigenin on sepsis complications. Google Scholar, Scopus, Web of Science, PubMed and Embase databases were searched for relevant keywords up to August 2025. Results A total of 421 articles were screened in the databases. Finally, only 30 studies remain. Evidence from in vivo and in vitro studies indicates that Apigenin modulates key signalling pathways, such as Rho-associated coiled-coil containing protein kinase (ROCK)/Ras homolog family member A (RhoA)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Peroxisome Proliferator-activated receptor gamma (PPARγ)/microRNA-21 (miR-21) and Kelch-like eCH-associated protein 1 (KEAP1)/Nuclear factor erythroid 2-related factor 2 (Nrf2), to alleviate sepsis-induced damage in organs such as the lungs, intestines, heart and kidneys. Additionally, Apigenin promotes macrophage polarization towards the M2 macrophage phenotype (M2) phenotype and reduces proinflammatory cytokines (Interleukin-6 (IL-6), Tumour necrosis factor alpha (TNF-α), Interleukin-1 beta (IL-1β), Conclusion Despite its promising effects, further clinical trials are needed to confirm its efficacy and safety in septic patients.

Background Early-stage breast cancer (BC) shows heterogeneous recurrence risk. Circulating tumor DNA (ctDNA) is promising non-invasive biomarker for minimal residual disease and recurrence prediction, though prognostic performance varies by assay and context. Methods Eligible studies on ctDNA-based recurrence and survival were identified through comprehensive searches, quality assessed, and analyzed using random-effects meta-analysis to estimate pooled hazard ratios for clinical outcomes. Heterogeneity (I2, τ2, Cochran’s Q), subgroup (detection method or assay type), and sensitivity analyses were performed to examine the consistency and robustness of results. Results For recurrence-free survival endpoints, the pooled HR was 3.28 [95% CI: 1.81; 5.93], indicating a high risk of recurrence-related events among ctDNA-positive patients, though substantial heterogeneity was observed (I2 = 93.3%). Pooled effect sized for overall survival (8.92 HR [0.45; 177.87], I2 = 74.7%) and recurrence/relapse (5.21 [0.98; 27.69], I2 = 84.4%) indicating substantial heterogeneity. Subgroup analysis showed lower heterogeneity with digital PCR and personalized ctDNA assays, and sensitivity testing confirmed result stability (2.47 [1.89; 3.23], I2 = 0%). Conclusion CtDNA positivity, detected through mutation-based assays strongly associated with increased risk for early recurrence in early-stage BC. Digital PCR and personalized assays demonstrated superior consistency; however, prospective trials are needed to establish its clinical utility.

Background Clear cell renal cell carcinoma (ccRCC) accounts for over 75% of all renal cancer and contributes significantly to cancer-associated mortality. This study aims to identify a new ccRCC biomarker. Methods Univariate and multivariate Cox regression models were performed for prognostic analysis. Differentially expressed genes (DEGs) were identified based on high and low expression AFAP1L1 groups. Functional enrichment analysis was conducted on the DEGs. Immunoassays were conducted on immune checkpoints, immune cells, and other components. Single-cell expression of AFAP1L1, along with associated pseudo-temporal trajectory analyses, was evaluated. The Connectivity Map was employed to identify potentially small-molecules. AFAP1L1 mRNA expression was measured via quantitative real-time PCR (qRT-PCR) experiment. Results AFAP1L1 was significantly upregulated in training cohort and qRT-PCR, and lower expression level was correlated with shorter overall survival, which was also confirmed in E-MTAB-1980 and CPTAC validation cohorts. The upregulated DEGs were primarily involved in signaling pathways, nephron development, and transporter activity. AFAP1L1 was positively related with neutrophils and macrophages. AFAP1L1 exhibited a relatively higher expression level in endothelial cells at the single-cell level. Five potential therapeutic agents targeting ccRCC were identified. Conclusions AFAP1L1 may impact the ccRCC development and progression, acting as an immune-related prognostic marker for ccRCC.

Background Gastric cancer (GC) is the fifth leading cause of cancer‐related death worldwide, with a median overall survival of approximately 12 months. The proto‐oncogene c-MYC is among the most frequently activated oncogenes, implicated in roughly 20% of all malignancies. Methods PubMed, Embase, and Web of Science were systematically searched for studies evaluating the association between c-MYC expression and (1) disease-specific survival (DSS) and (2) overall survival (OS). Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using a fixed-effects model. A two-sided p ≤ 0.05 was considered statistically significant. Results Across 15 studies encompassing 2,372 gastric cancer patients (802 c-MYC–positive; 410 male), male gender was strongly associated with c-MYC positivity (OR 8.83; 95% CI 5.74–13.56; p < 0.00001), as were deeper invasion (T3–T4 vs T1–T2: OR 0.38; 95% CI 0.24–0.60; p < 0.00001) and advanced stage (III–IV vs I–II: OR 2.69; 95% CI 1.71–4.23; p < 0.00001). Patients with c-MYC–negative tumors exhibited a markedly higher DSS compared to those with c-MYC–positive tumors (HR 3.73; 95% CI, 2.22–6.26; p < 0.0001). Conclusion Our findings identify c-MYC as a significant prognostic biomarker for disease‐specific survival in gastric cancer.

Background Pancreatic Stone Protein (PSP) has been proposed as a sepsis biomarker, but its role in severity stratification in pediatric intensive care and its relation to infectious source have not been explored. Methods We conducted a retrospective analysis of 97 pediatric patients admitted to the PICU with new-onset sepsis (within 24h from diagnosis). Blood samples were collected within 24h to measure PSP levels and compared with microbiological culture results. Results Among 97 patients, PSP levels were significantly higher in those with positive blood cultures (n = 24; median 108 ng/mL) compared with negatives (n = 73; 82 ng/mL, p = 0.008). When combining blood molecular testing with cultures, PSP remained higher in positives (n = 31; 111 ng/mL) than negatives (n = 66; 85 ng/mL, p = 0.026). PSP levels also correlated with sepsis severity: Non-septic (n = 55, median 72 ng/mL), sepsis (n = 22, median 238 ng/mL), septic shock (n = 20, 375 ng/mL) (p = 0.001). Receiver operating characteristic (ROC) curve analysis showed that PSP had superior accuracy in predicting sepsis severity (AUC 0.75, 95% CI 0.64-0.87) compared with C-reactive protein (C-RP, AUC 0.54, 95% 0.37-0.64) and procalcitonin (PCT, AUC 0.60, 95% CI 0.35-0.67). Conclusions PSP is a promising biomarker for sepsis detection and severity prediction in critically ill pediatric patients. Further studies are required to validate its integration into diagnostic protocols.

Objective The aim of this study is to see the association of P-selectin, E-selectin, Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intercellular Adhesion Molecule-1 (ICAM-1) with Vaso-occlusive crisis (VOC) in sickle cell disease patients. Methods In this longitudinal study, a total of 140 SCD patients admitted into a Government Medical College, Jabalpur, were recruited. Plasma levels of soluble P-selectin, E-Selectin, ICAM-1, and VCAM-1 were measured at three different time points, that is, (i) at the time of admission (n = 140), (ii) at discharge (n = 139), and (iii) during steady state (n = 118). Results The most common presenting symptoms at the time of VOC were severe joint pain (65.7%) and back pain (49.3%). All the cell adhesion molecule levels were similar in males and females except sVCAM-1. The plasma P-selectin, E-Selectin, ICAM-1 and VCAM-1 levels were significantly higher during crisis than at the discharge and steady state. No statistically significant association of any of the CAM levels with the severity of pain was observed. High plasma VCAM-1 levels (≥1676 ng/mL) were associated with longer duration of hospital stay. Conclusions Significant association of soluble CAMs with VOC in SCD suggests that soluble CAMs play a crucial role in the pathophysiology of the VOC.

Objective To examine the role and diagnostic potential of miR-421 in prostate cancer (PCa). Methods Expression data and clinical information for miR-421 were obtained from the TCGA and Genotype-Tissue Expression (GTEx) databases. Experimental validation was performed at the cellular, blood, and tissue levels to confirm miR-421 expression and its association with clinicopathological features. ROC curves were drawn on the bioinformatic study using TCGA data. The target genes of miR-421 were predicted via four online databases, and protein interaction associations were analyzed for intersecting targets. Gene Ontology (GO) analysis was subsequently conducted to assess functional relevance. Results MiR-421 was significantly overexpressed in prostate cancer (PCa) patients, a finding validated in cell, blood, and tissue samples. ROC analysis on the bioinformatic study using TCGA data revealed that miR-421 reliably differentiated PCa tissues from normal tissues. Higher miR-421 expression was associated with an elevated Gleason score, advanced TNM stage, and metastasis. GO enrichment analysis indicated that the target genes of miR-421 were significantly related to diverse molecular functions. Conclusions MiR-421 is a promising biomarker for diagnosing and predicting PCa.

Objective The current study aimed to determine the roles of pivotal and novel lncRNAs associated with the cell cycle in the occurrence and development of Colorectal cancer (CRC). Methods The TCGA-COAD project related to CRC was downloaded, and differential expression analysis was performed to identify differentially expressed lncRNAs, miRNAs, and mRNAs. A cell cycle-associated lncRNA-miRNA-mRNA regulatory network was constructed, and two novel lncRNAs were selected. Two subnetworks were constructed for selected lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were illustrated for the genes in each sub-network. qPCR analysis was used to validate the expression levels of the selected lncRNAs in CRC tissues compared to those adjacent normal tissues. Results The differential expression analysis identified 416 lncRNAs, 317 miRNAs, and 117 mRNAs. The ceRNA subnetwork genes were associated with different pathways, including cellular senescence, DNA replication, human T-cell leukemia virus 1 infection, and oocyte meiosis. The bioinformatic results based on the TCGA project indicated the dysregulation of two novel lncRNAs, MIR29B2CHG and HELLPAR, in CRC tissues compared to adjacent normal tissues. Moreover, qPCR confirmed the dysregulation of lncRNAs in the CRC tissues. ROC curves revealed that both selected lncRNAs had acceptable specificity and sensitivity as biomarkers. Conclusion In conclusion, novel cell cycle-associated lncRNAs have the potential to be understood as the underlying molecular mechanisms that influence CRC. Therefore, these lncRNAs can be considered as promising biomarkers for the diagnosis and treatment of CRC.

Background Gastric cancer (GC) is a major global cause of cancer mortality, with a median overall survival of just 12 months. CLDN18.2, a specific isoform of Claudin18 normally expressed in the gastric mucosa, has emerged as a potential therapeutic target and prognostic biomarker due to its exposure on the surface of tumor cells following malignant transformation. This exposure allows CLDN18.2’s extracellular loops to bind monoclonal antibodies, presenting new opportunities for targeted therapy and improved prognostic assessment. Methods A comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Science databases was conducted for studies that addressed the correlation of CLDN18.2 with: (1) Progression-free survival (PFS) and (2) Overall Survival (OS). Hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs) were calculated using a fixed-effects model. Heterogeneity was examined with I 2 statistics. P values of ≤ 0.05 were considered statistically significant. Statistical analyses were performed using RStudio, version 4.2.3. Results A total of 15 studies encompassing a total of 4,085 patients were included. There were 2,691 (65.8%) male and 1,394 (34.2%) female patients. In the histologic GC analysis, there were 1,582 (38.7%) patients that had intestinal type and 1,280 (31.3%) with diffuse type. Patients with CLDN18.2 negative status exhibited a non-significant trend towards prolonged PFS (HR: 1.25; 95% CI: 0.98–1.61; p = 0.07; I 2 = 18%) and a significant prolonged OS (HR: 1.20; 95% CI: 1.07–1.34; p < 0.01; I 2 = 37%) when compared to CLDN18.2-positive patients. Conclusion Our findings establish CLDN18.2 as a robust negative prognostic indicator for overall survival in GC patients. While its impact on PFS was not statistically significant, the association with OS suggests CLDN18.2 may serve as a marker for complex biological processes underlying tumor advancement.

Objective The objective of this study was to compare the levels of cathepsin B and pentraxin 3 in maternal serum of pregnant women with preeclampsia in the second trimester, to ascertain the impact of these levels on maternal and fetal outcomes, and to present a comprehensive analysis of the combined effects of cathepsin B and pentraxin 3 levels. Methods This prospective case-control study was conducted at Bursa Yuksek Ihtisas Training and Research Hospital between 1 January 2022 and 31 December 2022. The study included 78 pregnant women diagnosed with preeclampsia and 78 healthy pregnant women in the second trimester, between the ages of 18 and 45. Once a diagnosis of preeclampsia was established, maternal serum samples were obtained from the pregnant women prior to the initiation of any therapeutic intervention. Once all samples had been collected, the values for cathepsin B and pentraxin 3 were determined using the ELISA method. Results The results demonstrated a statistically significant elevation in the levels of pentraxin 3 (p = 0.008) and cathepsin B (p = 0.005) in pregnancies affected by preeclampsia when compared to those deemed healthy. Moreover, pentraxin-3 (p = 0.007) and cathepsin B (p = 0.002) were found to be significantly elevated in severe preeclampsia compared to mild preeclampsia. A comparison of the groups with and without HELLP syndrome revealed no statistically significant difference between the two groups. The ROC analysis revealed that the Cathepsin B 7.04 cut-off value was statistically significantly associated with the prediction of preeclampsia in all cases, with a sensitivity of 78.2% and a specificity of 47.4% (p = 0.005, AUC = 0.631). Conclusion The levels of CB and PTX3 may be employed as biomarkers to facilitate the early diagnosis of PE during the second trimester. Furthermore, these biomarkers may prove to be promising for the prediction of PE severity.