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Recent evidence suggests that EpCAM and CD44 could serve as diagnosis or prognosis markers in pancreatic cancer (PC). In this meta-analysis, we evaluated their associations with clinicopathologic features. Specifically, we compared immunohistochemical-positive and -negative PC patients for T stage (T3-T4 vs. T1-T2), N stage (N1 vs. N0), M stage (M1 vs. M0), tumor grade (well/moderately vs. poorly differentiated), UICC Stage (III, IV vs. I, II), and overall survival (OS). The diagnostic meta-analysis was performed analysing the pooled sensitivity and specificity and evaluating overall accuracy to indicate the diagnostic efficacy of the markers. The protocol of this systematic review and meta-analysis was registered on the PROSPERO website under the registration number of CRD42024568390. A systematic search of PubMed, Scopus, and ISI Web of Science was conducted on January 30th, 2025. The statistical analysis was performed using the Review Manager 5.4 software and R language (R package Mada and Metafor). The quality of the studies included was assessed using the Newcastle-Ottawa scale and the QUADAS-2 tool. Data from relevant studies were independently screened and extracted using Rayyan, by at least two authors. A total of 19 studies were eligible (9 studies for EpCAM, 9 studies for CD44, and 2 studies for both EpCAM and CD44), comprising a total of 1370 patients. The diagnostic meta-analysis demonstrated moderate accuracy for EpCAM (AUC, 95% CI of 0.802, 0.69–0.96). A statistically significant association was found for CD44 expression and T-status (OR = 2.04, 95%CI = 1.18–3.51), or N-stage (OR = 2.68, 95%CI = 1.86–3.85), or TNM stage (OR = 3.79, 95%CI = 2.14–6.71). CD44v6 overexpression predicted worse OS (HR = 2.33, p  < 0.00001), while EpCAM + CD44 + co-expression was prognostic (HR = 2.02, p  = 0.02). Heterogeneity was not observed among the studies included, but further research is warranted to better understand the clinical implications of these markers’ positivity in PC diagnosis and prognosis.

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.

Background: In the last few decades, it has been emphasized that dopamine, a well-known neurotransmitter with multiple roles in central nervous system, is also implicated in the activity of peripheral tissues and organs, more specifically influencing the gastrointestinal system (GI). Methods: We registered a protocol under the CRD42024547935 identifier in the Prospero register of systematic reviews. Furthermore, using the Population, Intervention, Comparison, Outcome, and Study Design strategy to guide our study rationale, and under the Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations, we conducted a qualitative systematic literature search based on the PubMed, Scopus, and Web of Science databases using the “gastric cancers AND dopamine” search criteria. We obtained 68 articles from PubMed, 142 articles from Scopus, and 99 articles from the Web of Science database. Results: Within gastric cancer biology, dopamine has notable effects on STAT-3 and DARPP-32. STAT-3, a transcription factor involved in cellular proliferation and invasion, plays a significant role in cancer progression. Conclusions: Understanding the roles of dopamine in cancer, beyond aspects such as cancer cell invasion, immune response modulation, or tumor growth, could guide the development of new cancer therapies by modulating its pathways, especially the DARPP-32/CXCR4/CXCL-12 complex axis, in order to improve the morbidity and mortality caused by this type of cancer.

Colorectal cancer (CRC) remains one of the most important global health problems, being in the top 3 neoplasms in terms of the number of cases worldwide. Although CRC develops predominantly from the adenoma–adenocarcinoma sequence through APC gene mutations, in recent years, studies have demonstrated the role of chronic inflammation in this neoplasia pathogenesis. Cytokines are important components of chronic inflammation, being some of the host regulators in response to inflammation. The pro-inflammatory cytokines IL-1β, IL-6, and TNF-α are involved in tumor cell proliferation, angiogenesis, and metastasis and seem to strengthen each other’s mode of action, these being stimulated by the same mediators. In our study, we collected data on 68 patients with CRC and 20 healthy patients from the Gastroenterology Department of Craiova County Emergency Clinical Hospital, who were assessed between January 2022 and February 2023. The main purpose of this study was to investigate the correlation between increased plasma levels of the cytokines and the extent of the tumor, lymph nodes, and metastasis—(TNM stage), as well as the patients’ prognoses. We also compared the plasma levels of cytokines and acute inflammatory markers, namely, the erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and fibrinogen, along with the tumor markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19.9), in CRC patients. We showed that all the pro-inflammatory cytokines studied had higher levels in patients with CRC in comparison with the control group. We also showed that the acute inflammatory markers of erythrocyte sedimentation rate, C-reactive protein, and fibrinogen, and the tumor markers of CEA and CA 19.9 can be useful in diagnosis and prognosis in patients with CRC. Considering the association between pro-inflammatory cytokines and CRC, the development of new targeted therapies against IL-1β, IL-6, and TNF-α can improve patient care and the CRC survival rate.

Systemic inflammation has an important role in the prognosis and progression of many chronic diseases, including diabetes (T2DM). This retrospective study aimed to evaluate inflammatory status by determining the serum inflammatory biomarkers (PTX3, hs-CRP, TNF-α, and IL-6) and new indices, like the mean corpuscular volume (MCV) to lymphocyte ratio (MCVL) and cumulative inflammatory index (IIC), in a cohort of patients with prediabetes (PreDM) and newly diagnosed T2DM. We also wanted to assess the association with clinical parameters and different obesity-related indices, to identify possible correlations and to evaluate the diagnostic accuracy of the biomarkers using ROC curve analysis. In this study, we included 60 patients diagnosed with T2DM and 30 patients with PreDM. The ELISA method was applied. Elevated PTX3, hs-CRP, TNF-α, and IL-6 levels were found in T2DM patients compared to preDM patients. An independent relationship was found between PTX3, hs-CRP, and different obesity-related indices in patients with preDM and T2DM. The MCVL index exhibited an inverse trend proportional to the rising levels of HbA1c in the T2DM group. Spearman’s analysis revealed in the T2DM group that the PTX3 values correlated much better with IIC (rho = 0.445, p-value = 0.014) and MCVL (rho = 0.338, p-value = 0.048). Hs-CRP values expressed moderate-to-weak correlations with IIC and MCVL in both groups. Additionally, ROC analysis showed that the PTX3 (AUC was 0.720; p = 0.003; cut-off value 1888.00 pg/mL, with 67.60% sensitivity and 73.30% specificity) and MCVL index (AUC was 0.677; p = 0.047; cut-off value 39.60, with 63.30% sensitivity and 66.70% specificity) have a good, accurate diagnosis compared with IL-6 (AUC was 0.866; p < 0.0001; cut-off value 40.30 pg/mL, with 100.00% sensitivity and 60.00% specificity). IIC showed 61.70% sensitivity and 60.00% specificity, with an AUC of 0.572, p = 0.027 and a cut-off value of 2.35. PTX3 and MCVL can serve as independent predictor factors in the inflammatory status in preDM and T2DM patients, supporting their potential as biomarkers for T2DM management and future research.

Prediabetes and early type 2 diabetes mellitus (T2D) are increasingly recognized as states of both metabolic and neurochemical dysregulation. This narrative review synthesizes emerging evidence of alterations in key neurotransmitter systems—dopamine, serotonin, norepinephrine, gamma-aminobutyric acid, and glutamate—in individuals with prediabetes and diabetes. Beyond peripheral insulin resistance and β-cell dysfunction, disturbances in the central nervous system, especially related to neurotransmitter signaling, may play a role in disease onset and progression. Neuroimaging studies reveal early imbalances in excitatory and inhibitory neurotransmitters, while biochemical and histological findings demonstrate altered receptor expression in both the brain and pancreatic islets. These changes affect metabolic control and are implicated in mood, cognition, and feeding behavior. We investigate the mechanistic links between neurotransmitter dysfunction and glucose metabolism, including the roles of brain insulin resistance, inflammation, mitochondrial stress, and gut–brain axis signaling. Finally, we discuss therapeutic strategies that target neurochemical pathways and highlight the need for longitudinal, sex-aware, and multi-omics studies to refine early interventions. Understanding the neurobiological roots of early T2D could revolutionize risk assessment and open doors for new neuro-metabolic treatments.

Neurotransmitters play a pivotal role not only in central nervous system signaling but also in the regulation of systemic energy metabolism, insulin sensitivity, and cardiovascular function. The contribution of neuroendocrine dysregulation to the development of type 2 diabetes mellitus (T2DM) is increasingly being recognized; however, the interplay between neurotransmitter levels and lipid/insulin resistance profiles in T2DM and prediabetes (PreDM) remains poorly characterized. We evaluated serum dopamine (DA), norepinephrine (NE), epinephrine (EPI), and serotonin (ST) in 110 individuals with PreDM (n = 40) or newly diagnosed T2DM (n = 70). Extended metabolic profiling included HbA1c, lipid panels, and insulin resistance indices (triglyceride-to-glucose index (TyG), TyG-derived indices). Neurotransmitter levels were compared across body mass index (BMI) categories, gender, and glycosylated hemoglobin A1c (HbA1c) quartiles. We applied multivariable linear regression (MLR) adjusted for body mass index (BMI), age, sex, lipids, penalized logistic regression (predicting T2DM status), and exploratory Spearman correlations with False Discovery Rate (FDR) correction. All four neurotransmitters were significantly higher in T2DM versus PreDM (p < 0.001). In T2DM patients, DA and NE levels increased across HbA1c quartiles, and NE levels were significantly higher in quartile 3 compared to quartile 2 (p = 0.045). In multivariable models, T2DM status was the only consistent predictor of neurotransmitter elevations. Logistic regression identified ST (OR = 8.70) and NE (OR = 3.76) as key discriminators of T2DM status, in addition to HbA1c. Exploratory correlation analyses in T2DM showed trends between EPI and insulin resistance indices (TyG adjusted for waist circumference (TyG-WC), TyG adjusted for waist-to-height ratio (TyG-WHtR)) and between DA and low-density lipoprotein cholesterol (LDL-C), although these did not survive to FDR correction. Neurotransmitter levels are elevated in T2DM and correlate with glycemic and metabolic profiles, suggesting early neuroendocrine involvement in the pathogenesis of diabetes. Serotonin and norepinephrine may serve as adjunctive biomarkers for disease stratification, meriting further prospective and mechanistic investigation.

We compared oxidative markers and their links to inflammation in diabetic nephropathy and hemodialysis to identify independent determinants. We studied 180 adults, 90 patients with type 2 diabetes and diabetic nephropathy and 90 patients on hemodialysis. We measured serum advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS) by enzyme-linked immunosorbent assay (ELISA). Partial correlations were adjusted for age, sex, and albumin with false discovery rate (FDR) control. Principal component analysis (PCA) summarized inflammatory indices and linear models tested predictors of AOPP and TBARS. Oxidative damage was higher in hemodialysis, with AOPP median 25.80 versus 5.06 and TBARS 8.49 versus 1.89, p less than 0.0001. C reactive protein (CRP) and mean corpuscular volume-to-lymphocyte ratio (MCVL) were higher in patients ongoing hemodialysis; systemic immune-inflammation index (SII) was higher in diabetic nephropathy. PCA yielded a dominant inflammation axis in both cohorts, 74.73 percent in hemodialysis and 85.20 percent in diabetic nephropathy. In regression, creatinine (β = 2.47, p = 0.026) predicted AOPP in hemodialysis. Dialysis vintage inversely predicted TBARS, β = −0.2305, p = 0.0209. In diabetic nephropathy, the PCA inflammation score predicted AOPP, β = 1.134, p = 0.0003. Protein oxidation tracked systemic inflammation in diabetic nephropathy, but not in hemodialysis. AOPP outperformed TBARS as an inflammatory partner and a practical monitoring candidate in diabetic kidney disease. Prospective studies should test for prognostic value and therapy sensitivity.

Neuroendocrine tumors are uncommon in the gastrointestinal system but can develop in the majority of the body’s epithelial organs. Our goal was to examine the presence and clinical application of serum dopamine (DA), serotonin (ST), norepinephrine (NE), and epinephrine (EPI), in addition to determining the significance of the Prognostic Nutritional Index (PNI), Glasgow Prognostic Score (GPS), and systemic inflammatory response (SIR) markers as a prognostic factor for patients with colorectal neuroendocrine tumors (CR-NETs), in various tumor–node–metastasis (TNM) stages. We also wanted to identify the possible connection between them. This study included 25 consecutive patients who were diagnosed with CR-NETs and a control group consisting of 60 patients with newly diagnosed colorectal cancer (CRC). We used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. This study revealed that CR-NET patients showed significantly higher serum levels of DA compared to CRC patients. We showed that serum DA was present in the early stages of CR-NETs, with increasing levels as we advanced through the TNM stages. Moreover, we found a close relationship between the levels of DA and the inflammation and nutritional status of the CR-NET patients in this study. CR-NET patients from the PNI < 47.00 subgroup had a higher level of DA than those from the PNI ≥ 47.00 subgroup. Pearson’s correlation analysis revealed correlations between DA, PNI, and the neutrophil/lymphocyte ratio (NLR) and the platelet/lymphocyte ratio (PLR). Both hematological indices were negatively correlated with albumin (ALB). Our investigation’s findings relating to the PNI, GPS, SIR, and DA indicate that these tools can be markers of nutritional and systemic inflammatory status, are simple to use, and are repeatable. Further research on this topic could provide valuable insights into which biomarkers to incorporate into clinical practice for the management of CR-NET patients.

Colorectal cancer is one of the most widespread types of cancer that still causes many deaths worldwide. The development of new diagnostic and prognostic markers, as well as new therapeutic methods, is necessary. The calcitonin gene-related peptide (CGRP) neuropeptide alongside its receptor calcitonin receptor-like receptor (CRLR) could represent future biomarkers and a potential therapeutic target. Increased levels of CGRP have been demonstrated in thyroid, prostate, lung, and breast cancers and may also have a role in colorectal cancer. At the tumor level, it acts through different mechanisms, such as the angiogenesis, migration, and proliferation of tumor cells. The aim of this study was to measure the level of CGRP in colorectal cancer patients’ serum by enzyme-linked immunosorbent assay (ELISA) and determine the level of CGRP and CRLR at the tumor level after histopathological (HP) and immunohistochemical (IHC) analysis, and then to correlate them with the TNM stage and with different tumoral characteristics. A total of 54 patients with newly diagnosed colorectal adenocarcinoma were evaluated. We showed that serum levels of CGRP, as well as CGRP and CRLR tumor level expression, correlate with the TNM stage, with local tumor extension, the presence of lymph node metastasis, and distant metastasis, and also with the tumor differentiation degree. CGRP is present in colorectal cancer from the incipient TNM stage, with levels increasing with the stage, and can be used as a diagnostic and prognostic marker and may also represent a potentially new therapeutic target.