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"Boldeanu, Mihail-Virgil"
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Correlation of the Pro-Inflammatory Cytokines IL-1β, IL-6, and TNF-α, Inflammatory Markers, and Tumor Markers with the Diagnosis and Prognosis of Colorectal Cancer
by
Boldeanu, Mihail-Virgil
,
Șerban, Robert-Emmanuel
,
Serbanescu, Mircea-Sebastian
in
Adenocarcinoma
,
Angiogenesis
,
Antigen-presenting cells
2023
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.
Journal Article
Expression of Calcitonin Gene-Related Peptide and Calcitonin Receptor-like Receptor in Colorectal Adenocarcinoma
by
Boldeanu, Mihail-Virgil
,
Șerban, Robert-Emmanuel
,
Constantin, Cristian
in
Adenocarcinoma
,
Adenocarcinoma - blood
,
Adenocarcinoma - metabolism
2024
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.
Journal Article
Systematic Review: Maternal Risk Factors, Socioeconomic Influences, Neonatal Biomarkers and Management of Early-Onset Sepsis in Late Preterm and Term Newborns—A Focus on European and Eastern European Contexts
by
Vulcănescu, Anca
,
Boldeanu, Mihail-Virgil
,
Siminel, Mirela-Anișoara
in
Antibiotic resistance
,
Antibiotics
,
At risk populations
2025
Early-onset sepsis (EOS) remains a major cause of neonatal morbidity and mortality worldwide, with significant differences in the incidence and outcome of the disease in Europe. Eastern European countries face particular challenges due to differences in access to healthcare, diagnostic facilities, and prevention strategies. This review summarizes the results of recent research to provide insights into maternal risk factors, regional inequalities in access to healthcare, diagnostic biomarkers, pathogen patterns, and treatment protocols for EOS. This review also examines how healthcare infrastructure and socioeconomic factors influence EOS outcomes in Eastern Europe. Introduction: Early-onset sepsis (EOS) presents a significant health challenge for newborns, characterized by sepsis occurring within the first 72 h of life, primarily caused by the vertical transmission of pathogens from mother to child. Despite advancements in medical care, EOS remains particularly burdensome in resource-poor settings, especially in Eastern Europe, where disparities in healthcare access and maternal health are pronounced. This systematic review aims to provide insights into maternal risk factors, regional inequalities in healthcare access, diagnostic biomarkers, pathogen patterns, and treatment protocols for EOS. Background/Objectives: EOS is increasingly recognized as a public health issue, with outcomes significantly influenced by maternal health, socioeconomic status, and healthcare infrastructure. The review seeks to summarize the existing literature on EOS, particularly focusing on differences between high-income Western and low-resource Eastern European countries. The influence of maternal access to antenatal care, pathogen prevalence, and antibiotic resistance on EOS outcomes across regions will also be examined. Methods: To achieve the review’s objectives, a comprehensive search was conducted across multiple databases including PubMed, Google Scholar, ScienceDirect, and Scopus, adhering to PRISMA guidelines for systematic reviews. The inclusion criteria encompassed studies published within the last 20 years (January 2004–August 2024) that addressed EOS in late preterm or term infants, emphasizing maternal health, risk factors, diagnostic approaches, and treatment protocols pertinent to European populations. Exclusion criteria included non-English publications and studies lacking a focus on maternal and neonatal health. A total of 29 peer-reviewed articles meeting the specified criteria were ultimately included in the analysis. Results: The findings highlight significant regional disparities in EOS management between Western and Eastern Europe. Key issues include maternal risk factors, socioeconomic barriers to healthcare, diagnostic biomarkers, and pathogen resistance trends. Limited access to prenatal screenings and healthcare infrastructure in Eastern European countries, especially in rural regions in Romania, exacerbate the challenges faced by expectant mothers. Financial burdens, such as high out-of-pocket expenses, were shown to further restrict access to necessary maternal care. Conclusions: This systematic review emphasizes the urgent need for targeted investments in maternal healthcare infrastructure in Eastern Europe to mitigate the impacts of EOS. Enhanced screening programs, standardized surveillance systems, and ensuring equitable health policies are essential to improving neonatal outcomes. Additionally, tailored education and awareness campaigns for disadvantaged groups and comprehensive health policy reforms, including universal antenatal care and Group B Streptococcus (GBS), are essential to bridging healthcare gaps.
Journal Article
The Diagnostic and Prognostic Role of Inflammatory Markers, Including the New Cumulative Inflammatory Index (IIC) and Mean Corpuscular Volume/Lymphocyte (MCVL), in Colorectal Adenocarcinoma
by
Boldeanu, Mihail-Virgil
,
Șandru, Vasile
,
Popescu, Dragoș-Marian
in
Adenocarcinoma
,
Blood platelets
,
Blood tests
2025
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.
Journal Article
Correction: Vulcănescu et al. Systematic Review: Maternal Risk Factors, Socioeconomic Influences, Neonatal Biomarkers and Management of Early-Onset Sepsis in Late Preterm and Term Newborns—A Focus on European and Eastern European Contexts. Life 2025, 15, 292
by
Vulcănescu, Anca
,
Boldeanu, Mihail-Virgil
,
Siminel, Mirela-Anișoara
in
Infants (Newborn)
,
Neonatology
2025
In the original publication [...]
Journal Article
Association between Serum 8-Iso-Prostaglandin F2α as an Oxidative Stress Marker and Immunological Markers in a Cohort of Preeclampsia Patients
by
Manolea, Maria Magdalena
,
Boldeanu, Mihail Virgil
,
Siloși, Isabela
in
8-iso-prostaglandin F2-alpha
,
Biomarkers
,
Blood pressure
2023
Background: We aimed to analyze the presence and clinical use of serum 8-iso-prostaglandin F2-alpha (8-iso-PGF2α) as an oxidative stress marker and some inflammatory status biomarkers (tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL-10, high-sensitivity C-reactive protein (hs-CRP), and pentraxin-3 (PTX3)) for patients with preeclampsia (PE). Methods: Sixty pregnant women, including thirty diagnosed with PE and thirty who were healthy (NP), were included in this study. For the assessment of serum levels of biomarkers, we used the Enzyme-Linked Immunosorbent Assay (ELISA) technique. Results: Our preliminary study showed that the expression level of serum 8-iso-PGF2α in the PE group was higher than in the PE after delivery (PE-AD) group (742.00 vs. 324.00 pg/mL, p < 0.0001). Groups of preeclamptic patients (PE + PE-AD) expressed significantly elevated levels for all of the assessed inflammatory mediators as compared to NP. Significant strong positive correlations with 8-iso-PGF2α levels were found for systolic blood pressure (SBP), and TNF-α (Spearman’s rho = 0.622, p-value = 0.020 and rho = 0.645, p-value = 0.002, respectively). Our study demonstrates that 8-iso-PGF2α and PTX3 have the greatest diagnostic value for pregnant women with PE. Conclusions: 8-iso-PGF2α and PTX3 can be used as independent predictor factors, along with already-known cytokines, that could represent a prophylactic way to help clinicians identify or predict which pregnant women will develop PE.
Journal Article
Intersecting Pathways of Inflammation, Oxidative Stress, and Atherogenesis in the Evaluation of CKD: Emerging Biomarkers PCSK9, EPHX2, AOPPs, and TBARSs
by
Assani, Mohamed-Zakaria
,
Boldeanu, Mihail Virgil
,
Stroe-Ionescu, Alexandra-Ștefania
in
Analysis
,
Arteriosclerosis
,
Atherogenesis
2025
Chronic kidney disease (CKD) is a multifactorial disorder increasingly recognized as a systemic condition marked by persistent inflammation, oxidative stress, dyslipidemia, and endothelial dysfunction. Diabetic nephropathy, a leading cause of CKD, amplifies cardiovascular risk through intertwined mechanisms beyond traditional risk factors. This review synthesizes current evidence on the interplay between inflammation, oxidative stress, and atherosclerosis in CKD, with a special focus on emerging molecular biomarkers—PCSK9, EPHX2, AOPPs, and TBARSs—and their integration with clinical indices. These markers illuminate pathophysiological networks underlying CKD progression and cardiovascular complications, offering novel insights into risk stratification, disease monitoring, and targeted therapy. By exploring molecular and clinical intersections, this review underscores the potential of a personalized, biomarker-driven approach to CKD management.
Journal Article
Pregnancy Under Pressure: Oxidative Stress as a Common Thread in Maternal Disorders
by
Assani, Mohamed-Zakaria
,
Boldeanu, Mihail Virgil
,
Siloși, Isabela
in
8-Hydroxydeoxyguanosine
,
Angiogenesis
,
Antioxidants
2025
Oxidative stress, defined as the imbalance between reactive oxygen species (ROS) and antioxidant defenses, plays a pivotal role in the pathogenesis of several pregnancy complications, notably preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and recurrent pregnancy loss (RPL). During normal pregnancy, low to moderate ROS levels support essential placental functions such as angiogenesis and trophoblast differentiation. However, excessive ROS production overwhelms antioxidant systems, leading to lipid peroxidation, protein and DNA damage, and impaired placental function. This review synthesizes current evidence linking oxidative stress to adverse pregnancy outcomes, highlighting key biomarkers such as malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-iso-prostaglandin F2α (8-iso-PGF2α). While antioxidant therapies—particularly vitamins C and E, selenium, and folic acid—have shown promise in reducing oxidative markers, their impact on clinical outcomes remains inconsistent. The variability in results underscores the need for standardized biomarker protocols and personalized treatment strategies based on genetic predispositions and baseline oxidative status. Future research may better harness antioxidant interventions to improve maternal–fetal health by addressing these gaps.
Journal Article
The Influence of Fixed Dental Prostheses on the Expression of Inflammatory Markers and Periodontal Status—Narrative Review
by
Boldeanu, Virgil Mihail
,
Boldeanu, Lidia
,
Gheorghe, Dorin Nicolae
in
Analysis
,
Dental crowns
,
Dental Prosthesis
2023
A dental prosthesis will only be successful if the restoration lasts for a long period and does not cause any illness. The presence of permanent prosthetic restorations has been linked to an increased risk of periodontal infections, according to a large body of research that has been gathered. When chronic inflammation is brought on by fixed prosthetic constructions, both cellular and noncellular immunity are activated as adaptive immune mechanisms. It has previously been stated that both clinically adequate and inadequate restorations might cause gingival inflammation. Areas surrounding the abutment teeth presented periodontal pockets, attachment loss, congestion, bleeding on probing, and gingival hyperplasia after fixed restorations were removed. The depth of pockets, bleeding on probing, and bone loss are all closely correlated with disease’s severity and IL-1β concentration in gingival crevicular fluid; IL-1β shows higher values in disease sites than in healthy ones. hs-CRP and TNF-α blood levels showed a considerable reduction one day after fixed restorations were applied, in comparison with the pre-treatment values. Collaboration between prosthodontists and periodontists is essential for a good treatment outcome since it will increase the restoration’s lifespan, enhance periodontal health, and improve the quality of life for dental patients.
Journal Article
Correlation Between Prognostic Nutritional Index, Glasgow Prognostic Score, and Different Obesity-Related Indices in People with Diabetes or Prediabetes
by
Vladu, Ionela Mihaela
,
Clenciu, Diana
,
Mitrea, Adina
in
body adiposity index
,
Body mass index
,
Care and treatment
2024
Background/Objectives: The prognostic nutritional index (PNI) and Glasgow Prognostic Score (GPS) are associated with patients’ nutritional and immune statuses. One important factor in the pathophysiology of type 2 diabetes mellitus (T2DM) is inflammation. Being present in insulin-target tissues, chronic tissue inflammation has become recognized as a crucial aspect of obesity and type 2 diabetes. This study aimed to compare the PNI and GPS levels of the subjects with T2DM to those of prediabetes (preDM) individuals. Furthermore, the goal was to investigate how these inflammatory markers relate to different types of obesity and whether the combination of PNI, GPS, and obesity-related indices was associated with any particular prognostic variables. Methods: In this study, we enrolled one-hundred patients with newly diagnosed T2DM and one-hundred patients with preDM. Results: Four findings emerged from this observational study. As a first observation, 28% of patients with preDM and 15% of patients with T2DM had a normal weight, while up to 43% of patients with preDM and 60% of patients with T2DM were obese. The second important observation was that the PNI of the T2DM patients was significantly lower than the PNI of the patients with preDM (p < 0.0001). The PNI showed that patients with T2DM had a moderate-to-severe malnutrition status (median value of 38.00). Patients with preDM had a mild-to-moderate malnutrition status (median value of 61.00) at diagnosis. Third, observed in the current study, preDM patients with PNI < 61.00 and T2DM patients with a PNI < 38.00 were associated with significantly higher median values of the waist-to-height ratio (WHtR) (p = 0.041, and p = 0.034, respectively) and body mass index (BMI) (p = 0.016, and p = 0.041, respectively). Fourth, this study also revealed, in the T2DM group, a moderate and statistically significant negative correlation between PNI and weight (rho = −0.322, p = 0.035), waist circumference (WC) (rho = −0.308, p = 0.042), hip circumference (HC) (rho = −0.338, p = 0.039), WHtR (rho = −0.341, p = 0.022), body adiposity index (BAI) (rho = −0.312, p = 0.032), and fasting plasma glucose (FPG) (rho = −0.318, p = 0.029). Additionally, the PNI values expressed a weak negative correlation with BMI (rho = −0.279, p = 0.015), and glycated hemoglobin A1c (HbA1c) (rho = −0.245, p = 0.025). The PNI levels exhibited a single positive correlation, weak but statistically significant, with estimated glomerular filtration rate (eGFR-CKD-EPI) values (rho = 0.263, p = 0.018). Conclusions: The findings of this study regarding the correlations between PNI, GPS, and different obesity-related indices in people with diabetes or prediabetes suggest that these indices, which assess nutritional and inflammatory status, can be used as independent predictor factors associated with the four pillars of DM management (glucose, blood pressure, lipids, and weight control) recommended by the American Diabetes Association (ADA).
Journal Article