Evidence has shown that ibuprofen and celecoxib are effective in improving depressive symptoms, but their mechanisms of action are unclear. In this study, we aimed to determine the relationship between these two drugs and depressive disorder (DD) and elucidate potential mechanisms of action.

Relevant targets for ibuprofen, celecoxib, and DD were obtained and screened from multiple online drug and disease public databases. A protein-protein interaction network was obtained. The Centiscape and CytoHubba plug-ins were applied to screen for core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. Molecular docking was performed to predict the binding of ibuprofen and celecoxib to core targets. Examined the differences in core target protein expression between DD patients (DDs, n = 18) and healthy controls (HCs, n = 16) as a further experimental validation of the network pharmacology results.

In total, 220 potential targets for ibuprofen and 316 potential targets for celecoxib were identified and associated with DD. The antidepressant effects of both drugs involve many key targets in pathways such as "pathways in cancer" and "neuroactive ligand-receptor interaction," including ALB, BCL2, MAPK3, SRC, STAT3, EGFR, and PPARG. The binding affinity of ALB with ibuprofen is the strongest, and it is connected only by hydrophobic interactions. Celecoxib exhibits higher affinity at multiple targets such as SRC, EGFR, and PPARG, with stronger and more specific intermolecular interactions, including salt bridges and halogen bonds. Clinical trials have found that serum ALB expression in DDs is significantly lower than that in HCs (t = 6.653, p < 0.001), further confirming the potential role of ibuprofen in DD.

Ibuprofen and celecoxib primarily exert their antidepressant effects through targets and pathways related to inflammation, neural signaling, and cancer, with celecoxib showing a stronger potential antidepressant effect. The expression difference of the core target ALB between depression and healthy individuals further supports the potential effect of the drug on DD. Our findings propose new treatment strategies, support the link between inflammation and depression, and encourage reassessing existing medications for depression.

To explore the association of remnant cholesterol (RC) and lipoprotein-associated phospholipase A2 (Lp-PLA2) with composite adverse events in a large-scale prospective study.

All data were collected from the Asymptomatic Polyvascular Abnormalities Community study between 2010 and 2022. Serum cholesterol levels and Lp-PLA2 were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their RC and Lp-PLA2 levels: low-RC/Lp-PLA2-, high-RC/Lp-PLA2-, low-RC/Lp-PLA2+ and high-RC/Lp-PLA2+. The composite endpoint was a combination of first-ever stroke, myocardial infarction or all-cause mortality. Cox regression analyses were performed to evaluate associations of RC and Lp-PLA2 with composite adverse events.

Of the 1864 eligible participants, the average age was 60.6 years, and 74.3% were male. Over a follow-up of 12 years, we identified 500 composite adverse events, including 210 major adverse cardiovascular events and 342 all-cause deaths. When compared with the group of low-RC/Lp-PLA2-, the hazard ratios with 95% confidence intervals in the group of high-RC/Lp-PLA2+ for stroke, myocardial infarction, major adverse cardiovascular event, all-cause death and composite endpoints were 1.37 (0.87-2.16), 0.72 (0.28-1.82), 1.29 (0.85-1.95), 1.61 (1.10-2.38) and 1.43 (1.07-1.91), respectively. A significant interaction between RC and Lp-PLA2 status has been found for all-cause death and composite endpoint (p for interaction <0.05). In addition, joint association of RC and Lp-PLA2 with all-cause death was modified by sex and age of <60 versus ≥60 years (p for interaction: 0.035 and 0.01, respectively).

Elevated RC and Lp-PLA2 levels were associated with an increased risk of composite adverse events, with these associations significantly influenced by sex and age. Our study highlights the synergistic effect of RC and Lp-PLA2 on the composite adverse events.

To develop a deep learning-based method for robust and rapid estimation of the fatty acid composition (FAC) in mammary adipose tissue.

A physics-based unsupervised deep learning network for estimation of fatty acid composition-network (FAC-Net) is proposed to estimate the number of double bonds and number of methylene-interrupted double bonds from multi-echo bipolar gradient-echo data, which are subsequently converted to saturated, mono-unsaturated, and poly-unsaturated fatty acids. The loss function was based on a 10 fat peak signal model. The proposed network was tested with a phantom containing eight oils with different FAC and on post-menopausal women scanned using a whole-body 3T MRI system between February 2022 and January 2024. The post-menopausal women included a control group (n = 8) with average risk for breast cancer and a cancer group (n = 7) with biopsy-proven breast cancer.

The FAC values of eight oils in the phantom showed strong correlations between the measured and reference values (R2 > 0.9 except chain length). The FAC values measured from scan and rescan data of the control group showed no significant difference between the two scans. The FAC measurements of the cancer group conducted before contrast and after contrast showed a significant difference in saturated fatty acid and mono-unsaturated fatty acid. The cancer group has higher saturated fatty acid than the control group, although not statistically significant.

The results in this study suggest that the proposed FAC-Net can be used to measure the FAC of mammary adipose tissue from gradient-echo MRI data of the breast.

The prognostic significance of the C-reactive protein-albumin-lymphocyte (CALLY) index in digestive system neoplasms (DSNs) has been investigated in several studies, but inconsistencies remain between the results of different studies. Therefore, the aim of this study was to confirm the prognostic significance of CALLY in patients with DSNs and its association with clinicopathological characteristics (CPCs).

The databases PubMed, Cochrane Library, Web of Science, Research Square and Embase were systematically searched for clinical trials with databases up to 1 November 2024. The value of CALLY in predicting overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) versus cancer-specific survival (CSS) in patients with DSNs was confirmed by calculating the combined hazard ratio (HR) and 95% CI. The combined OR and 95% CI were calculated to assess the association between CALLY and CPCs in patients with DSNs.

A total of 18 studies with 7916 patients with DSNs were included in this study. Pooled analysis showed that lower CALLY was associated with poor OS, DFS, RFS and CSS were significantly associated. In addition, low CALLY index was associated with male gender, T3-T4, lymph node metastasis, lymph vessel invasion, complications, stage III-IV and surgical approach were significantly associated. However, there was no association between low CALLY index and histological type, adjuvant chemotherapy, and neoadjuvant chemotherapy.

In this meta-analysis, a low CALLY index was significantly associated with poor OS, DFS, RFS and CSS in patients with DSNs and with several CPCs in patients with DSNs.

PROSPERO CRD42024622973.

Viewing the hallmarks as a sequence of adaptations captures the "why" behind the "how" of the molecular changes driving cancer. This eco-evolutionary view distils the complexity of cancer progression into logical steps, providing a framework for understanding all existing and emerging hallmarks of cancer and developing therapeutic interventions.

The ketogenic diet (KD) has attracted attention in recent years for its potential anticancer effects. KD is a dietary structure of high fat, moderate protein, and extremely low carbohydrate content. Originally introduced as a treatment for epilepsy, KD has been widely applied in weight loss programs and the management of metabolic diseases. Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells, thereby inhibiting tumor angiogenesis, reducing oxidative stress in normal cells, and affecting cancer cell signaling and other processes. Moreover, KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota, enhance the efficacy of standard cancer treatments, and mitigate the complications of chemotherapy. However, controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer. Therefore, this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.

Breast cancer (BC) is the leading cancer among women globally, which has the highest incidence and mortality rate in over a hundred countries. This study was intended to discover a new prognostic biomarker, facilitating personalized treatment approaches.

RNA sequencing data from The Cancer Genome Atlas database and Gene Expression Omnibus database were utilized to download to evaluate expression levels and prognostic significance of Keratin 14 (KRT14). Methylation of KRT14 was also assessed. The CIBERSORT and single-sample gene set enrichment analysis algorithms were applied to explore the connection between KRT14 and the tumor microenvironment. Primary drugs' sensitivity and potential small molecule therapeutic compounds were analyzed through the "pRRophetic" R package and the Connectivity Map. The prognostic value of KRT14 was additionally corroborated through a comparison of protein levels in peritumoral and cancerous tissues via immunohistochemistry. Moreover, an immune-related prognostic model based on KRT14 was designed to enhance the prediction accuracy for the prognosis of BC patients.

The study found that KRT14 expression was generally downregulated in BC, correlating strongly with poor prognosis. Compared to normal tissues, the methylation level of KRT14 was higher in BC tissues. Lower expression of KRT14 was linked to decreased anti-tumoral immune cells infiltration and increased immunosuppressive cells infiltration. Sensitivity to various key therapeutic drugs was lower in groups with diminished KRT14 expression. In addition, several potential anti-BC small molecule compounds were identified. The model designed in this study significantly enhanced the predictive capability for BC patients compared to predictions based solely on KRT14 expression levels.

Overall, KRT14 was closely correlated with the prognosis in BC, making it a reliable biomarker.

A systemic analysis was performed to evaluate the prognostic utility of the Glasgow prognostic score (GPS) and the modified (m)GPS in cancer patients treated with immune checkpoint inhibitors (ICI). The PubMed, Cochrane Library, EMBASE and Google Scholar databases were searched for entries added until May 1st, 2023, to obtain relevant articles for this study. The analysis examined several clinical outcomes, including overall survival (OS), progression-free survival (PFS), objective response rate and disease control rate (DCR). In this analysis, a total of 38 articles with 3,772 patients were included. The pooled results indicated that patients with high GPS levels had shorter OS [GPS 2 vs. 0, hazard ratio (HR): 4.35, P<0.001; GPS 1 vs. 0, HR: 2.00, P<0.001; GPS 2 vs. 1/0, HR: 2.62, P<0.001; GPS 2/1 vs. 0, HR: 2.60, P<0.001) and PFS (GPS 2 vs. 0, HR: 2.11, P=0.001; GPS 1 vs. 0, HR: 1.33, P=0.001; GPS 2 vs. 1/0, HR: 2.11, P<0.001; GPS 2/1 vs. 0, HR: 1.62, P<0.001], as well as a lower DCR [GPS 2 vs. 1/0, odds ratio (OR): 0.53, P<0.001, GPS 2/1 vs. 0, OR: 0.51, P<0.001]. It was also found that patients with high mGPS levels had poorer OS (mGPS 2 vs. 0, HR: 3.15, P<0.001; mGPS 1 vs. 0, HR: 1.70, P<0.001; mGPS 2 vs. 1/0, HR: 1.95, P=0.049; mGPS 2/1 vs. 0, HR: 3.14, P=0.041; continuous variables, HR: 1.52, P<0.001) and PFS (mGPS 2 vs. 0, HR: 2.70, P<0.001; mGPS 1 vs. 0, HR: 1.74, P=0.016; mGPS 2 vs. 1/0, HR: 1.91, P=0.044; continuous variables, HR: 1.29, P<0.001), and lower DCR (mGPS 2 vs. 1/0, HR: 0.46, P<0.001). In conclusion, the GPS and mGPS were reliable predictors of outcomes in cancer patients treated with ICIs.

Pancreatic cancer is an aggressive malignancy characterized by rapid progression, unfavorable outcomes, and a low early detection rate. Elucidating the mechanisms underlying the onset and progression of pancreatic tumors is essential for early detection and for developing preventive measures. Even though human rhomboid family-1 (RHBDF) acts as an oncogene in various tumors, the role of RHBDF in pancreatic cancer progression remains unexplored. Here, publicly available datasets, including samples of chronic pancreatitis associated with pancreatic cancer from our center, were used for bioinformatics analyses, including differential expression, survival, and enrichment studies. The findings were validated by immunohistochemical staining and in vitro experiments. We found that RHBDF1 was significantly upregulated in tumor samples relative to adjacent non-tumor and pancreatitis tissues, and its expression increased in correlation with the progression of pancreatitis to cancer. Furthermore, RHBDF1 promoted the proliferation, migration, and invasion of pancreatic cancer cells, and in vivo studies demonstrated that RHBDF1 promoted pancreatic cancer progression, tissue fibrosis, and the formation of new blood vessels. RNA-sequencing and cell functional experiments indicated that RHBDF1 promotes the progression of pancreatic cancer through the SRC-YAP signaling pathway. In summary, the pancreatitis-cancer transformation-related factor, RHBDF1, promotes pancreatic cancer progression by activating the SRC-YAP signaling cascade, indicating that RHBDF1 could be a viable target for the diagnosis and treatment of early-stage pancreatic cancer.

Chronic inflammation is a common hallmark of many chronic diseases. Although exercise holds paramount importance in preventing and managing chronic diseases, adherence to exercise programs can be challenging for some patients. Consequently, there is a pressing need to explore alternative strategies to emulate the anti-inflammatory effects of exercise for chronic diseases.

This review explores the emerging role of green tea bioactive components as potential mitigators of chronic inflammation, offering insights into their capacity to mimic the beneficial effects of exercise. We propose that bioactive components in green tea are promising agents for suppressing chronic inflammation, suggesting their unique capability to replicate the health benefits of exercise.

This review focuses on several key concepts, including chronic inflammation and its role in chronic diseases, the anti-inflammatory effects of regular exercise, and bioactive components in green tea responsible for its health benefits. It elaborates on scientific evidence supporting the anti-inflammatory properties of green tea bioactive components, such as epigallocatechin gallate (EGCG), and theorizes how these bioactive components might replicate the effects of exercise at a molecular level. Through a comprehensive analysis of current research, this review proposes a novel perspective on the application of green tea as a potential intervention strategy to suppress chronic inflammation, thereby extending the benefits akin to those achieved through exercise.

The very prevalent nature, genetic variability, and intricate tumor microenvironment (TUME) of colorectal cancer (COREC) are its defining features. In order to better understand the molecular and cellular make-up of COREC, this work used single-cell RNA sequencing (SRNAS) to isolate and characterize important cell types as well as their interactions within the TUME. Our analysis of 51,204 cells yielded six distinct types: epithelial, fibroblast, endothelial, T&NK, B, and myeloid. C3 B cells were shown to be the most active in immunological regulation, according to chemokine signaling study, which was one of seven clusters of B cells that were thoroughly subtyped. The examination of copy number variation (CONUV) revealed a great deal of genetic variability, especially in epithelial cells. We traced the activity of three key transcription factor clusters (M1, M2, and M3) across all B cell subtypes using transcription factor analysis. We created a predictive model that correctly sorts patients according to survival results by using marker genes from C3 B cells. In addition, the relationship between genetic changes and the immune system was better understood by tumor mutational burden (TUMUB) and immune infiltration studies. Our research sheds light on the genetic complexity and cellular variety of COREC, which in turn opens up new possibilities for targeted treatments and individualized approaches to patient care.

Mycobacterium tuberculosis (Mtb) causes 1.25 million deaths a year. However, tuberculosis (TB) pathogenesis remains poorly understood and is not fully recapitulated in standard mouse models. Here we find that gene signatures from three different Mtb-susceptible mouse models predict active TB disease in humans significantly better than a signature from resistant C57BL/6 (B6) mice. Conserved among susceptible mice, non-human primates, and humans, but largely absent from B6 mice, was Mtb-induced differentiation of macrophages into an Spp1+ differentiation state. Spp1+ macrophages expressed high levels of immunosuppressive molecules including IL-1 receptor antagonist (IL-1Ra). IL-1Ra was previously reported to cause Mtb susceptibility in one mouse model, but whether IL-1Ra is broadly important remains uncertain. Here we report that enhancement of IL-1 signaling via deletion of IL-Ra promoted bacterial control across three susceptible mouse models. We found IL-1 signaling amplified production of multiple cytokines by lymphoid and stromal cells, providing a multifactorial mechanism for how IL-1 promotes Mtb control. Our results indicate that myeloid cell expression of immunosuppressive molecules, in particular IL-1 receptor antagonist, is a conserved early mechanism limiting Mtb control in mice, non-human primates, and humans.

Multiple myeloma has become the second most common hematologic malignancy threatening human health with the increasing incidence in the population, and the emergence of drug resistance in its treatment has become a problem that needs to be solved urgently. Recent studies have shown that the immune system is closely related to the development of multiple myeloma, and immune senescence plays an extremely critical role in MM treatment resistance. In this paper, we review the connection between immune senescence and the development of MM and its possible role in the drug resistance of MM treatment, to provide new research ideas for the in-depth study of the mechanism of immune senescence and the search for new immunotherapeutic targets to overcome the phenomenon of drug resistance in the immunotherapy of MM patients.

Programmed necrosis, a controlled cell death method that bypasses resistance mechanisms that render apoptosis ineffective, is a potential cancer treatment target. Due to their diverse biological activities and low side effects, natural products are being explored as modulators of programmed necrosis pathways. This review highlights the potential of natural compounds to target cancer cells while preserving healthy tissues and their interaction with essential programmed necrosis mechanisms like ferroptosis and necroptosis. Recent developments have identified various types of programmable necrosis, including necroptosis, ferroptosis, pyroptosis, proptosis, mitochondrial permeability transition-driven necrosis, and oncosis. Natural compounds are increasingly being utilized as a primary source of anti-cancer medications, providing new cancer treatments. This review demonstrates the molecular mechanisms behind lipid peroxidation, mixed lineage kinase domain-like protein, and receptor-interacting protein kinases (RIPK1 and RIPK3) inducing cell death. Recent research has identified natural compounds like polyphenols, alkaloids, and terpenoids that can modulate pathways and benefit preclinical cancer models. The review underscores the potential of natural compounds in developing innovative cancer treatments by integrating pharmacology and cellular signaling knowledge. Integrating natural compound studies and programmed necrosis research presents a promising avenue for oncologists to overcome treatment resistance. Natural compounds have shown potential in developing programmed necrosis as a novel cancer treatment approach, enhancing therapeutic effectiveness and minimizing side effects through preclinical research, pharmacology, and molecular biology.

The human microbiome, an intricate ecosystem of trillions of microbes residing across various body sites, significantly influences cancer, a leading cause of morbidity and mortality worldwide. Recent studies have illuminated the microbiome's pivotal role in cancer development, either through direct cellular interactions or by secreting bioactive compounds such as metabolites. Microbial metabolites contribute to cancer initiation through mechanisms such as DNA damage, epithelial barrier dysfunction, and chronic inflammation. Furthermore, microbial metabolites exert dual roles on cancer progression and response to therapy by modulating cellular metabolism, gene expression, and signaling pathways. Understanding these complex interactions is vital for devising new therapeutic strategies. This review highlights microbial metabolites as promising targets for cancer prevention and treatment, emphasizing their impact on therapy responses and underscoring the need for further research into their roles in metastasis and therapy resistance.

This study intends to examine any possible correlation between monocyte-to-lymphocyte ratio (MLR) and cardiovascular diseases (CVD).

Data from the 1999-2020 National Health and Nutrition Examination Survey (NHANES) in the USA were analyzed. Heart attacks, angina pectoris, congestive heart failure (CHF), coronary heart disease (CHD), and stroke were all covered by CVD. The independent relationships between these cardiovascular events and MLR levels, as well as other inflammatory indices (system inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), and C-reactive protein-to-albumin ratio (CAR)), were investigated. Furthermore, interaction tests and subgroup analysis were performed. Diagnostic capacities were also predicted and compared using receiver operating characteristic (ROC) curves.

Males made up 49.63% of the 46,289 people who were recruited in this study. The prevalence of CVD and its events were as follows: CHF at 2.99%, CHD at 3.72%, angina pectoris at 2.57%, heart attacks at 3.94%, and stroke at 3.48%, with CVD itself at 7.98%. MLR and CVD were positively correlated. Specifically, smooth curve fittings also found a non-linear relationship between MLR and CVD. Moreover, higher MLR levels were linked to increased rates of CHF, CHD, and strokes. SIRI was also found to have a positive correlation with CVD. MLR outperformed other inflammatory indices (SIRI, AISI, and CAR) in terms of discriminative capacity and accuracy in predicting CVD, CHF, CHD, angina pectoris, heart attack, and stroke, according to ROC analysis.

Compared with other inflammatory indicators (SIRI, AISI, and CAR), MLR appears to be a better inflammatory index for predicting CVD, CHF, CHD, angina pectoris, heart attack, and stroke. American adults with elevated MLR and SIRI should be aware of the possible harm caused by CVD. Causal inference is, however, limited by the cross-sectional design and dependence on self-reported data. Further longitudinal studies are needed to validate these findings.

Obesity induces systemic perturbations of tissue homeostasis, leading to dyslipidemia, insulin resistance and chronic state of inflammation. Evidence from clinical and preclinical studies links excess of adiposity with increased cancer incidence and suggests that chronic inflammation may contribute to increased cancer risk in obese patients. Over the last decades of obesity research, multifaced and complicated effects of abnormal or excessive expansion of Adipose Tissue have been uncovered. In particular, it is widely described how obesity can exacerbate the tumorigenesis for instance by fueling soluble signals and adipokines and by enhancing tissue inflammation and altering the hormonal balance. Less is known about the paracrine effects of the cancer-associated adipocytes on the tumor cells and still poorly explored is the reciprocal communication between cancer cells and the adipose component of the tumor microenvironment (TME). In this review, we will address the mechanisms by which the peritumoral Adipose Tissue can influence the dynamics of tumoral cells. We will discuss how obesity-induced changes in the tumor microenvironment may enhance tumor growth and aggressive characteristics leading to increased invasiveness and metastatic progression of cancer that leads to a worsen cancer survival in obese subjects. We conclude that targeting the peritumoral adipose component of the TME would be a therapeutic option to prevent cancer development.

Multinucleated giant cells are commonly observed in various malignancies; however their clinical and biological significance remains largely unexplored and it has been hypothesised that the cells may play a role in vascular mimicry, tumour progression and tumour survival. This study aimed to investigate the expression of smooth muscle actin and CD31 in feline post-injection site fibrosarcomas, focusing on relationships between multinucleated giant cells presence, tumour grade, and vascular density to elucidate their potential role in tumour progression.

A total of 61 feline post-injection site fibrosarcomas, histologically graded into grades I, II, and III, were examined immunohistochemically. Smooth muscle actin immunoreactivity was detected in 57/61 (93.4%) cases. Multinucleated giant cells expressing CD31 were identified in 39/61 (63.9%) cases, predominantly in high-grade tumours, with a correlation observed between multinucleated giant cell presence, tumour grade, and mitotic index. Vascular density differed across tumour grades. A negative correlation between vascular density, tumour grade and necrosis score was identified. Additionally, a negative correlation was observed between multinucleated giant cells presence and vascular density.

The findings suggest a complex tumour microenvironment in which multinucleated giant cells and vascular mimicry may facilitate tumour survival under hypoxic conditions, potentially contributing to an aggressive tumour phenotype.

Cervical cancer is a prevalent form of cancer affecting women worldwide and it is the second most common cancer among women in Indonesia, accounting for 8.5% of all cancer-related deaths. Cervical cancer progression can be evaluated through laboratory tests to detect anaemia, an increased platelet count, and elevated inflammatory markers, therefore, effective laboratory examination is crucial for early detection and treatment of cervical cancer.

To evaluate the association between laboratory findings (haematology, haematology index, and inflammatory index) and the clinical stage of cervical cancer.

This cross-sectional study analyzed adult cervical cancer patients' data from medical records and laboratory results including sociodemographic status, histopathological finding, clinical stage, and complete haematology examination. Numerical data was analyzed by the one-way ANOVA (normal data distribution), while the Kruskal-Wallis test was used for non-parametric data (abnormal distribution), followed by appropriate post-hoc analysis. The categorical data was analyzed by the Chi-square or Fisher Exact tests. The significance level was established at a P value < 0.05.

This study involved the data of 208 adult cervical cancer patients and found no association between age, marital history, parity history, hormonal contraceptive use and cervical cancer stages. There were significant differences in the clinical laboratory test results based on the clinical stage of cervical cancer, including haemoglobin levels (P < 0.001), leucocytes (P < 0.001), neutrophils (P < 0.001), monocytes (P = 0.002), lymphocytes (P = 0.006), platelets (P < 0.001), neutrophil-lymphocyte ratio/NLR (P < 0.001), lymphocyte-monocyte ratio/LMR (P < 0.001), and platelet-lymphocyte ratio/PLR (P < 0.001). There were also significant differences in the systemic inflammatory index (SII) and systematic inflammatory response index (SIRI) between stage III + IV cervical cancer and stage II (SII P < 0.001; SIRI P = 0.001) and stage I (SII P < 0.001; SIRI P = 0.016), associated with the shifts in previously mentioned complete haematological values with cancer advancement.

The haematological parameters, inflammatory haematological ratios, and inflammatory indices exhibited significant differences between cervical cancer stages, therefore these tests can be utilized to evaluate cervical cancer progression.

The "Life's Essential 8" (LE8) is a comprehensive lifestyle assessment tool by the American Heart Association, designed to mitigate cardiovascular disease risk by optimizing lifestyle factors including diet, physical activity, and other health metrics. While individual components of LE8 have been linked to reduced cancer risks, comprehensive studies on LE8 score trajectories over time and their relation to cancer risk are lacking. This study employed the Kailuan cohort, involving 48,330 participants who underwent three health examinations from 2006 to 2010 to determine their LE8 scores. LE8 score trajectories were analyzed using latent mixture modeling, and their association with incident cancer risks was assessed through Cox proportional hazard models, adjusting for confounders such as age, biological sex, and lifestyle behaviors. Three distinct LE8 trajectory patterns were identified: low-stable (21.2%), moderate-stable (49.4%), and elevated-stable (29.4%). Participants with elevated-stable trajectories showed a 21% (HR = 0.79; 95% CI: 0.70-0.90), 27% (HR = 0.73, 95% CI: 0.57-0.92), 51% (HR = 0.49, 95% CI: 0.32-0.77), 31% (HR = 0.69, 95% CI: 0.50-0.97) and 39% (HR = 0.61, 95% CI: 0.39-0.95) reduction in overall, lung, breast, colorectal and liver cancer risk compared to those with low-stable scores. Notably, the protective effect of elevated-stable LE8 scores against breast cancer was pronounced in participants with elevated CRP levels, indicating an interaction between inflammation and LE8 trajectories. Maintaining high and stable LE8 scores significantly associated with reduced cancer risk, underscoring the importance of integrating LE8 into public health and clinical strategies for cancer prevention. Kailuan study, ChiCTR-TNRC-11,001,489. Registered August 24, 2011-Retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=8050 .

Chronic inflammation contributes to the development of colorectal cancer, partly through its regulation of the microenvironment and antitumor immunity. Interestingly, women have a lower incidence of colorectal cancer, and estrogen treatment has been shown to reduce the occurrence of colorectal tumors. While intestinal estrogen receptor beta (ERβ, Esr2) can protect against colitis and colitis-induced cancer in mice, its role in shaping the tumor microenvironment remains unknown. In this study, we performed RNA sequencing to analyze the transcriptome of colonic epithelia and tumors from azoxymethane/dextran sulfate sodium-treated wild-type and intestinal ERβ knockout (ERβKOVil) mice and vehicle-treated controls. This revealed significant differences in gene expression and enriched biological processes influenced by sex and genotype, with immune-related responses being overrepresented. Deconvolution supported differential immune cell abundance and immunostaining showed that tumors from ERβKOVil mice displayed significantly increased macrophage infiltration, decreased T cell infiltration, and impaired natural killer cell infiltration. Further, ERβ mRNA levels in clinical colorectal tumors correlated with immune signaling profiles and better survival. Our findings indicate that intestinal ERβ promotes an antitumor microenvironment and could potentially affect the effectiveness of immunotherapy. These insights highlight the importance of ERβ in modulating antitumor immunity and underscore its therapeutic potential in colorectal cancer.

Esophageal cancer is a major cause of cancer-related death, often preceded with chronic inflammation and injuries. The NFκB/IKKβ pathway plays a central role in inflammation, yet its role in early esophageal carcinogenesis remains unclear. This study investigated the role of epithelial IKKβ in early esophageal carcinogenesis. Mice were treated with the carcinogen 4-nitroquinoline-1-oxide (4-NQO) or a vehicle for one month to induce precancerous lesions. Esophagi were harvested and examined through histological, protein, flow cytometry, and RNA analyses. Histological analysis revealed that 4-NQO treatment led to increased inflammation, intraepithelial CD45+ immune cells, and elevated IKKβ phosphorylation levels. Mice with esophageal epithelial-specific Ikkβ deletion (4-NQO/ Ikkβ EEC-KO ) showed delayed progression to a precancerous state, with reduced immune cell recruitment compared to 4-NQO/controls. Immunophenotyping showed decreased recruitment of T cells, including CD4+, CD8+ and regulatory (Tregs) T cells, and increased recruitment of macrophages in 4-NQO/ Ikkβ EEC-KO mice compared to 4-NQO/controls. RNA sequencing data identified 262 differentially expressed genes in 4-NQO/ Ikkβ EEC-KO mice, implicating pathways related to inflammation and wound healing. Notably, the chemokine CXCL9, a T cell chemoattractant, was significantly upregulated in 4-NQO control mice, but not in 4-NQO/ Ikkβ EEC-KO mice. Further analysis identified IFNγ as an upstream regulator of Cxcl9 expression, and neutralization of IFNγ reduced Cxcl9 expression levels in 4-NQO treated mice. Additionally, in vitro studies demonstrated that IFNγ upregulates Cxcl9 in an NF-ĸB dependent manner in esophageal keratinocytes. These findings suggest that epithelial IKKβ regulates the immune microenvironment in early esophageal carcinogenesis through the IFNγ/CXCL9 axis and influencing T cell recruitment and inflammatory responses.

In a mouse model of early esophageal squamous cell carcinogenesis, loss of epithelial Ikkβ reduced inflammation and T cell recruitment, increased macrophage recruitment, inhibited IFNγ/CXCL9 signaling, and delayed the transition to a precancerous state.

Leukemia is a hematologic malignancy; acute lymphoblastic leukemia (ALL) is the most prevalent subtype among children rather than in adults. Orthoherpesviridae family members produce proteins during latent infection phases that may contribute to cancer development. One such protein, viral interleukin-10 (vIL-10), closely resembles human interleukin-10 (IL-10) in structure. Research has explored the involvement of human cytomegalovirus (hCMV) in the pathogenesis of ALL. However, the limited characterization of its latent-phase proteins restricts a full understanding of the relationship between hCMV infection and leukemia progression. Studies have shown that hCMV induces an inflammatory response during infection, marked by the release of cytokines and chemokines. Inflammation may, therefore, play a role in how hCMV contributes to oncogenesis in pediatric ALL, possibly mediated by latent viral proteins. The classification of a virus as oncogenic is based on its alignment with cancer's established hallmarks. Viruses can manipulate host cellular mechanisms, causing dysregulated cell proliferation, evasion of apoptosis, and genomic instability. These processes lead to mutations, chromosomal abnormalities, and chronic inflammation, all of which are vital for carcinogenesis. This study aims to investigate the role of vIL-10 during the latent phase of hCMV as a potential factor in leukemia development.

Only 15% to 20% of patients with pancreatic ductal adenocarcinoma (PDAC) have access to surgical resection, which represents the only chance of curative treatment. Current resection classifications are almost exclusively anatomic and do not correlate sufficiently with patient survival. It is essential to develop preoperative prognostic factors to distinguish patients at high risk of early postoperative recurrence from those who will have prolonged survival after surgery. In some cases, PDACs may present biomolecular differences reflecting their aggressiveness that are not yet assessable by the current clinical-biologic assessment. This study aimed to assess the preoperative prognostic factors that are already available and the future perspectives being developed.

This study reviewed the literature using the PubMed public database for preoperative prognostic factors for resectable PDAC.

Validated preoperative prognostic factors, whether clinical, biologic, radiologic, or histologic, are very important in anticipating the course of each patient's disease. The identification of potential new prognostic biomarkers such as genomic, transcriptomic, and proteomic analyses and the dosage of circulating tumor DNA are very serious avenues to be developed, but the extraction and analysis techniques as well as the interpretation of their results need to be standardized in prospective studies.

Cancer stands as a formidable malady profoundly impacting human health. Throughout history, plant-based therapies have remained pivotal in the arsenal against cancer, evolving alongside the epochs. Presently, challenges such as the arduous extraction of active components and potential safety concerns impede the progression of plant-based anticancer therapies. The isolation of plant-derived vesicle-like nanoparticles (PDVLNs), a kind of lipid bilayer capsules isolated from plants, has brought plant-based anticancer therapy into a novel realm and has led to decades of research on PDVLNs. Accumulating evidence indicates that PDVLNs can deliver plant-derived active substances to human cells and regulate cellular functions. Regulating immunity, inducing cell cycle arrest, and promoting apoptosis in cancer cells are the most commonly reported mechanisms of PDVLNs in tumor suppression. Low immunogenicity and lack of tumorigenicity make PDVLNs a good platform for drug delivery. The molecules within the PDVLNs are all from source plants, so the selection of source plants is crucial. In recent years, there has been a clear trend that the source plants have changed from vegetables or fruits to medicinal plants. This review highlights the mechanisms of medicinal plant-based cancer therapies to identify candidate source plants. More importantly, the current research on PDVLN-based cancer therapy and the applications of PDVLNs for drug delivery are systematically discussed.

Background/Objectives: Chronic inflammation has been implicated in cancer development, but the association between allergic rhinitis (AR) and head and neck cancer (HNC) remains unclear. This study aims to investigate this potential relationship using a population-based dataset. Methods: Utilizing the Taiwan Longitudinal Health Insurance Database 2010, we conducted a case-control study encompassing 14,913 HNC patients and 59,652 propensity-score matched controls. Multivariate logistic regression analyses were performed to quantitatively evaluate the association between HNC and prior AR, adjusting for demographic factors and medical comorbidities such as hyperlipidemia, diabetes, hypertension, tobacco use disorder, HPV infection, and alcohol-related disorders. Results: This study identified that 20.19% of the entire cohort had a prior diagnosis of AR, with a significantly higher prevalence in HNC patients relative to controls (26.2% vs. 18.70%). The adjusted odds ratio (OR) for previous AR in HNC patients was 1.559 (95% CI = 1.494-1.627). Furthermore, site-specific analysis revealed increased odds ratios for AR among patients with cancers of the larynx (OR = 1.537, 95% CI = 1.307-1.807), hypopharynx (OR = 1.220, 95% CI = 1.035-1.437), nasopharynx (OR = 2.933, 95% CI = 2.722-3.160), sinonasal (OR = 3.100, 95% CI = 2.424-3.964), salivary glands (OR = 1.470, 95% CI = 1.158-1.865), and thyroid (OR = 1.566, 95% CI = 1.447-1.693). Conclusions: The findings robustly support a significant link between AR and an elevated risk of developing HNC, notably affecting the nasopharynx, sinonasal cavities, larynx, salivary glands, and thyroid.

Many cancer patients develop resistance to immunotherapy, highlighting the urgent need for novel therapeutic strategies. Various factors contribute to tumor resistance to immunotherapy, among which tumor-associated macrophages (TAMs) are critical regulators of tumor sensitivity. Therefore, combining cancer immunotherapies with drug delivery systems (DDSs) targeting TAMs has become an intriguing treatment strategy. However, the target molecules used in DDSs are limited to a few receptors expressed on TAMs. Therefore, the identification of novel target molecules for TAM-specific DDS is urgently needed. The current study evaluated the ability of a cholesteryl pullulan (CHP) nanogel to target TAMs via mDC-SIGN (CD209b). This nanogel encapsulated the cytotoxic protein drug Pseudomonas exotoxin A and was injected into a tumor-bearing mouse model. This treatment significantly reduced the abundance of CD209b-positive M2 TAMs and enhanced antitumor immune responses. Ultimately, tumor growth was suppressed, even in a low-immunogenic tumor model. Hence, CD209b is an effective target molecule for M2 TAM-specific DDSs that can be used to develop novel cancer therapies.

The aim was to analyze the factors influencing the psychological status and cognitive function in postoperative head and neck tumor (HNT) patients. 170 patients, including 90 benign HNT (BHNT) patients and 80 malignant HNT (MHNT) patients, were included in this study. Psychological status was evaluated using the distress thermometer. Cognitive function was evaluated using the Multiple Ability Self-Reported Questionnaire. The psychological status and cognitive function were both statistically significantly better in BHNT patients than in MHNT patients (P < 0.001 and P < 0.001, respectively). MHNT patients in the moderate and severe appearance defect groups had a higher incidence of psychological distress than those in the no facial appearance defect group (P = 0.006 and P = 0.011, respectively). Both BHNT and MHNT patients in the group under the age of 60 had a higher incidence of psychological distress than those in the group over the age of 60 (P = 0.017 and P = 0.017, respectively). Educational level of both BHNT and MHNT patients was negatively correlated with the extent of cognitive impairment (P = 0.012 and P = 0.004, respectively). The influence of postoperative time on the psychological condition varied in different groups. Postoperative time of both BHNT and MHNT patients was negatively correlated with the extent of cognitive impairment (P = 0.027 and P < 0.001, respectively).

The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood. This trial tested the hypothesis that 12 wk of moderate-intensity aerobic exercise, when compared with a control group, would change inflammation, CTCs, and ctDNA in a manner consistent with an improved cancer prognosis.

This trial randomized Stages I-III colorectal cancer survivors to 12 wk of home-based moderate-intensity aerobic exercise or a waitlist control group. The co-primary endpoints were high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), secondary endpoints were soluble tumor necrosis factor-α receptor 2 (sTNFαR2) and circulating tumor cells (CTCs), and the exploratory endpoint was tumor fraction quantified from circulating tumor DNA.

Sixty subjects were randomized (age = 60.6 ± 10.8 years, mean ± SD; 39 (65%) females; 46 (77%) colonic primary tumor), and 59 (98%) subjects completed the study. Over 12 wk, exercise adherence was 92% (95% confidence interval (95%CI): 86‒99). Exercise improved submaximal fitness capacity (0.36 metabolic equivalents; 95%CI: 0.05‒0.67; p = 0.025) and objectively measured moderate-to-vigorous-intensity physical activity (34.8%, 95%CI: 11.3‒63.1; p = 0.002) compared to control. Exercise did not change hs-CRP (20.9%, 95%CI: -17.1 to 76.2; p = 0.32), IL-6 (11.4%, 95%CI: -7.5 to 34.0; p = 0.25), or sTNFαR2 (-3.6%, 95%CI: -13.7 to 7.7; p = 0.52) compared to control. In the subgroup of subjects with elevated baseline hs-CRP (n = 35, 58.3%), aerobic exercise reduced hs-CRP (-35.5%, 95%CI: -55.3 to -3.8; p = 0.031). Exercise did not change CTCs (0.59 cells/mL, 95%CI: -0.33 to 1.51; p = 0.21) or tumor fraction (0.0005, 95%CI: -0.0024 to 0.0034; p = 0.73). In exploratory analyses, higher aerobic exercise adherence correlated with a reduction in CTCs (ρ = -0.37, 95%CI: -0.66 to -0.08; p = 0.013).

Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.

Background: Colorectal cancer affects a large number of patients worldwide, with numerous factors being involved in its etiopathogenesis and chronic inflammation playing an essential role in tumor development. In this study, we analyzed and compared several markers of inflammation that are relatively easy to obtain for a rapid and accurate diagnosis and prognosis. Methods: This study included 219 patients diagnosed with colorectal cancer, analyzing the inflammation scores derived from their blood cells and inflammatory circulating proteins. These inflammatory markers are neutrophil-to-lymphocyte ratio-NLR; platelet-to-lymphocyte ratio-PLR; lymphocyte-to-monocyte ratio-LMR; systemic immune inflammation index-SII; systemic inflammatory response index-SIRI; aggregate index of systemic inflammation-AISI; derived neutrophil-to-lymphocyte ratio-dNLR; C-reactive protein-to-albumin ratio-CAR; and fibrinogen-to-albumin ratio-FAR. In the analysis of patients with colorectal cancer, we have also introduced two new recently developed inflammatory markers: the cumulative inflammatory index (IIC) and the ratio between the mean corpuscular volume and lymphocytes (MCVL). This study aimed to correlate the inflammatory markers' levels with the colorectal cancer diagnostic stage, the tumor and clinical characteristics of the colorectal cancer patients, and 36 months' survival time and to evaluate the diagnostic and prognostic capacity and accuracy of these inflammatory markers in this type of cancer. Results: We showed that the levels of the analyzed inflammation markers correlate with the TNM stage, the tumor pathological differentiation grade, the age and gender of the patients, and overall survival, with their increased levels being associated with a lower survival rate. Conclusions: The analyzed markers, which are easy to perform right from the patient's admission, can be helpful both in diagnosis and, mostly, in prognosis, sustaining the role of inflammation in cancer. By comparing them, we showed which one can be useful for increased sensitivity and specificity in the diagnosis and prognosis of colorectal cancer patients.

The stability of messenger RNA (mRNA) is controlled by proteins that bind to adenosine-uridine-rich sequences (AREs) in their 3' untranslated regions (3'UTR), known as AU-binding proteins. One of these proteins is tristetraprolin (TTP; encoded by Zfp36), which promotes degradation of mRNAs with AREs in their 3'UTR. TTP accelerates the decay of its target transcripts, many of which encode proinflammatory mediators that promote tumorigenesis. TTP underexpression has been reported in multiple cancer types. Oral squamous cell carcinoma is an aggressive disease characterized by high morbidity and few therapeutic options. The role of TTP has not been studied in oral epithelium homeostasis nor in its carcinogenesis. Herein, using tissue-specific TTP knockout mice (TTP-KO), we show that TTP expression is relevant for oral epithelium homeostasis. TTP-KO mice developed dysplastic lesions in the tongue along with inflammatory infiltrates in the connective tissue. Analysis of the inflammatory infiltrate revealed the presence of mast cells (MCs), CD45+ cells, and CD11b+ cells, with the MCs being the most abundant cell type and associated with cyclooxygenase-2 expression. Recruitment of MCs was dependent on tumor necrosis factor-α (TNFα) upon TTP ablation in the tongue. Although the infiltration of MCs was dependent on TNFα activity, this did not affect the development of tongue dysplasia. We analyzed the status of the NF-κB pathway, finding its activation. In addition, we demonstrate that K-ras activation combined with Zfp36 deletion leads to the rapid onset of the oral tongue phenotype and significantly reduces mouse survival. Our results support the notion that TTP expression protects against oral carcinogenesis, regulates the inflammatory infiltrate, and maintains the epithelial microenvironment, potentially serving as a barrier to tumorigenesis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a global public health and economic burden worldwide in the past few decades. Epidemiological studies have shown that MASLD is a multisystem disease that is associated not only with liver-related complications but also with an increased risk of developing extrahepatic cancers. MASLD is a sexually dimorphic disease with sex hormones playing an important role in the development and progression of MASLD, especially by the levels and ratios of circulating estrogens and androgens. MASLD is associated with hormone-sensitive cancers including breast and gynecological cancer. The risk of breast and gynecological cancer is elevated in individuals with MASLD driven by shared metabolic risk factors including obesity and insulin resistance. Multiple potential mechanisms underline these associations including metabolic dysfunction, gut dysbiosis, chronic inflammation and dysregulated release of hepatokines. However, the effect of hormone therapy including hormone replacement therapy and anti-estrogen treatment on MASLD and female-specific cancers remains debatable at this time. This synopsis will review the associations between MASLD and breast and gynecological cancer, their underlying mechanisms, implications of hormonal therapies, and their future directions.

We evaluated the prognostic significance of the Lactate Dehydrogenase-to-Serum Albumin Ratio (LAR), Fibrinogen-to-Albumin Ratio (FAR), and Platelet-to-Lymphocyte Ratio (PLR) in patients with high-grade urothelial carcinoma (HGUC) of the bladder who underwent radical cystectomy (RC). These markers have been reported to be associated with the prognosis of various cancers.

A retrospective analysis was conducted on HGUC patients who underwent RC at Guangxi Medical University Cancer Hospital between January 2013 and June 2021. Optimal cutoff values for LAR, FAR, and PLR were established. Kaplan-Meier survival analysis was used to evaluate survival outcomes, while univariate and multivariable Cox regression analyses identified independent prognostic factors. A nomogram was developed to predict survival, with validation through time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA).

A total of 180 patients were included, with a follow-up period ranging from 2 to 127 months (49.28 ± 37.87 months). The optimal cutoff values for LAR, PLR, and FAR were 4.46, 139.68, and 0.13, respectively. Multivariable Cox regression identified tumor stage, LAR, PLR, and FAR as independent prognostic factors. Specifically, Stage III (HR = 25.44, 95% CI: 5.20-124.35, p < 0.001) and Stage IV (HR = 11.28, 95% CI: 3.18-40.05, p < 0.001) were independent risk factors for poor survival. A low PLR (HR = 0.45, 95% CI: 0.27-0.76, p = 0.003), low FAR (HR = 0.51, 95% CI: 0.29-0.89, p = 0.018), and low LAR (HR = 0.39, 95% CI: 0.23-0.67, p < 0.001) were independently associated with improved survival. The nomogram demonstrated high accuracy in predicting 1-, 3-, and 5-year overall survival (OS), with area under the curve (AUC) values of 0.866, 0.84, and 0.831, respectively. Further validation confirmed the model's stability and clinical applicability.

LAR, PLR, and FAR are promising prognostic factors for HGUC of the bladder following RC, showing substantial potential for prognostic evaluation.

Non-coding RNAs (ncRNAs) have a significant role in gene regulation, especially in cancer and inflammatory diseases. ncRNAs, such as microRNA, long non-coding RNAs, and circular RNAs, alter the transcriptional, post-transcriptional, and epigenetic gene expression levels. These molecules act as biomarkers and possible therapeutic targets because aberrant ncRNA expression has been directly connected to tumor progression, metastasis, and response to therapy in cancer research. ncRNAs' interactions with multiple cellular pathways, including MAPK, Wnt, and PI3K/AKT/mTOR, impact cellular processes like proliferation, apoptosis, and immune responses. The potential of RNA-based therapeutics, such as anti-microRNA and microRNA mimics, to restore normal gene expression is being actively studied. Additionally, the tissue-specific expression patterns of ncRNAs offer unique opportunities for targeted therapy. Specificity, stability, and immune responses are obstacles to the therapeutic use of ncRNAs; however, novel strategies, such as modified oligonucleotides and targeted delivery systems, are being developed. ncRNA profiling may result in more individualized and successful treatments as precision medicine advances, improving patient outcomes and creating early diagnosis and monitoring opportunities. The current review aims to investigate the roles of ncRNAs as potential biomarkers and therapeutic targets in cancer and inflammatory diseases, focusing on their mechanisms in gene regulation and their implications for non-invasive diagnostics and targeted therapies. A comprehensive literature review was conducted using PubMed and Google Scholar, focusing on research published between 2014 and 2025. Studies were selected based on rigorous inclusion criteria, including peer-reviewed status and relevance to ncRNA roles in cancer and inflammatory diseases. Non-English, non-peer-reviewed, and inconclusive studies were excluded. This approach ensures that the findings presented are based on high-quality and relevant sources.

The microalga Aphanizomenon flos-aquae (AFA) has garnered attention for its potential therapeutic benefits in various health conditions, primarily through its use in nutraceutical formulations. While biological effects of AFA have been extensively studied in preclinical models, including murine systems, its nutrigenomic and epigenetic impacts remain underexplored. This study investigates the potential epigenetic mechanisms of AFA, focusing on its ability to modulate DNA methylation, a key regulatory process in gene expression. Specifically, we examined the influence of AFA on the methylation status of genes encoding pro-inflammatory interleukins, as these cytokines play a crucial role in immune response modulation and inflammation. Given the known impact of AFA on inflammatory markers, we aimed to determine whether the effects of AFA involve direct or indirect modulation of DNA methylation patterns in genes associated with inflammation. Our findings, presented here for the first time, reveal the capacity of AFA to influence DNA methylation, with implications for its role in cellular regulatory processes. These results warrant further investigation into precise mechanisms of action of AFA and its potential in clinical applications targeting inflammation-related pathways.

Background/Objectives: Renal cell carcinoma (RCC) accounts for 2-3% of all cancers, with approximately 25% of patients being detected at the metastatic stage. This study aimed to determine the prognostic significance of co-evaluating two risk parameters: one, the HALP score based on haemoglobin, albumin, lymphocyte, and platelet counts, and the other, albumin-to-alkaline phosphatase ratio (AAPR) in patients with metastatic RCC treated with targeted therapy. Methods: This retrospective cohort study included 147 patients with metastatic RCC. The HALP score and AAPR values were calculated from pre-treatment blood test results, and followingly, the cut-off value was determined by using ROC analysis. Patients were categorised into three groups with a low, moderate or high combined risk score based on this cut-off value. The effect of these risk groups on survival was evaluated. Results: The mean age of patients was 64.1 ± 11.9. The median follow-up time was 38.3 months, and the mortality rate was 53.7% in all groups. Kaplan-Meier survival analysis showed a statistically significant difference between the combined scores of the risk groups: the median survival time was 51.6 months in the low-risk group, 20.7 months in the medium-risk group, and 10.4 months in the high-risk group (p < 0.001), with 5-year survival rates being 38.8% in the low-risk group, 30% in the intermediate-risk group, and 19% in the high-risk group. When compared to the low-risk group, Cox regression analysis revealed that the mortality risk, i.e., HR (hazard ratio), was 2.42 times higher in the intermediate-risk group and 3.76 times higher in the high-risk group. A nephrectomy operation decreased the mortality risk (HR = 0.24) by 4.16 times. Conclusions: This new combined risk scoring, obtained from co-evaluating the HALP score and AAPR, was found to be an independent prognostic factor in metastatic RCC patients. This combined risk scoring is expected to help clinicians in treatment decisions.

Conservative anti-cancer treatment represented by chemotherapy and surgery lacks tumor-specificity and could hardly resolve the problems associated with multidrug resistance (MDR) in cancers. Novel therapeutic materials in cancer treatment, such as those with anti-MDR or controllable treatment features, represent a significant trend due to their advantages of high and specific efficacy and timely intervention of cancer progress. In addition to their excellent biocompatibility and specificity, they can be utilized in therapies that require ease of operation, provided they are designed with high detection sensitivity. In this review, we summarize a series of recently developed materials that exhibit these advantages, including immune-enhancing and tumor microenvironment (TME)- responsive materials, and those with integrated therapeutic and imaging capabilities. We also introduce advanced modification approaches that can impart essential targeting functionalities to these materials.

This study aimed to develop a prognostic model for colorectal cancer (CRC) patients using biomarkers from routine preoperative peripheral blood examinations combined with clinical factors.

This observational study comprised CRC patients (stages I-III) who underwent curative surgery between January 2011 and December 2019. Study variables included patient demographics, tumour characteristics, and immune/inflammatory markers from preoperative blood tests. Cut-off thresholds for continuous variables were determined using maximally selected rank statistics. Univariate and multivariate analyses identified variables associated with 3-year cancer-specific survival (CSS) and disease-free survival (DFS). Cox regression models were developed and validated using a random split-sample approach. Nomograms based on these models were constructed, and receiver operating characteristic (ROC) curves were generated for 12, 24 and 36 months.

A total of 764 patients were included. Independent factors for 3-year DFS included laparoscopic surgery, prognostic nutritional index (PNI), neutrophil count, lymphocyte count, and Charlson comorbidity index. The DFS prediction model showed AUC values of 66.6%, 64.8%, and 69% for years 1, 2, and 3, respectively. For CSS, independent factors included age, systemic immune-inflammation index (SII), serum albumin, and platelet count, with AUC values of 89.2%, 76.8%, and 71% for years 1, 2, and 3. The most significant contributors to the CSS model were SII and platelet cut-off values.

Inflammatory biomarkers combined with clinical parameters robustly predict 3-year survival outcomes in CRC patients undergoing curative resection. These findings highlight the importance of systemic inflammation in CRC prognosis and support its inclusion in preoperative risk stratification.

Choledocholithiasis has been reported to be associated with the occurrence of cholangiocarcinoma (CCA); however, the association has not yet been sufficiently demonstrated. This study aimed to evaluate the association between choledocholithiasis (common bile duct stones) and CCA.

This nationwide retrospective cohort study used the Health Insurance Review and Assessment database of individuals diagnosed with choledocholithiasis between 2008 and 2009 in South Korea. Individuals were stratified by age, and CCA was categorized into extrahepatic CCA (ECA) and intrahepatic CCA (ICA). The standardized incidence ratio (SIR) was calculated to compare CCA incidence between patients with choledocholithiasis and the general population.

The study enrolled 20,808 patients with choledocholithiasis (52.35% men and 47.65% women; male-to-female ratio: 1.09:1). Over a 10-year follow-up period, CCA occurred in 548 (2.64%) patients, comprising 238 (1.14%) ECA cases and 310 (1.48%) ICA cases. The SIR was 25.23 (95% confidence interval [CI]: 21.98-28.85) for ECA and 24.64 (95% CI: 21.87-27.73) for ICA. Statistical significance persisted even after excluding cases within the first 2 years from the index date, with an SIR of 18.63 (95% CI: 16.23-21.28) for ICA and 12.73 (95% CI: 10.50-15.30) for ECA. The SIRs peaked in patients diagnosed with choledocholithiasis at the age of 70-79 years (SIR 16.61, 95% CI: 11.83-22.69) for ECA and 60-69 years (SIR 29.27, 95% CI: 23.53-36.03) for ICA.

Our study demonstrated a significant association between choledocholithiasis and cholangiocarcinoma, particularly those in their 70s for ECA and 60s for ICA. However, causation cannot be established due to the retrospective design.

Inflammation is a multifaceted defense mechanism of the immune system against infection. Chronic inflammation is intricately linked to all stages of tumorigenesis and is therefore associated with an elevated risk of developing serious cancers. Epigenetic mechanisms have the capacity to trigger inflammation as well as facilitate tumor development and transformation within an inflammatory context. They achieve this by dynamically modulating the expression of both pro-inflammatory and anti-inflammatory cytokines, which in turn sustains chronic inflammation. The aberrant epigenetic landscape reconfigures the transcriptional programs of inflammatory and oncogenic genes. This reconfiguration is pivotal in dictating the biological functions of both tumor cells and immune cells. Aberrant histone H3 lysine 27 site (H3K27) methylation has been shown to be involved in biological behaviors such as inflammation development, tumor progression, and immune response. The establishment and maintenance of this repressive epigenetic mark is dependent on the involvement of the responsible histone modifying enzymes enhancer of zeste homologue 2 (EZH2), jumonji domain containing 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat gene X (UTX) as well as multiple cofactors. In addition, specific pharmacological agents have been shown to modulate H3K27 methylation levels, thereby modulating inflammation and carcinogenesis. This review comprehensively summarises the current characteristics and clinical significance of epigenetic regulation of H3K27 methylation in the context of inflammatory response and tumor progression.

Brain metastases are the most commonly diagnosed type of central nervous system tumor, yet the mechanisms of their occurrence are still widely unknown. Lung cancer, breast cancer, and melanoma are the most common etiologies, but renal and colorectal cancers have also been described as metastasizing to the brain. Regardless of their origin, there are common mechanisms for progression to all types of brain metastases, such as the creation of a suitable tumor microenvironment in the brain, priming of tumor cells, adaptations to survive spreading in lymphatic and blood vessels, and development of mechanisms to penetrate the blood-brain barrier. However, there are complex genetic and molecular interactions that are specific to every type of primary tumor, making the understanding of the metastatic progression of tumors to the brain a challenging field of study. In this review, we aim to summarize current knowledge on the pathophysiology of brain metastases, from specific genetic characteristics of commonly metastatic tumors to the molecular and cellular mechanisms involved in progression to the central nervous system. We also briefly discuss current challenges in targeted therapies for brain metastases and how there is still a gap in knowledge that needs to be overcome to improve patient outcomes.