Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review.

Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers-circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood tumor mutational burden (bTMB)-enhanced by next-generation sequencing (NGS) to improve the diagnostic accuracy, prognostic evaluation, and treatment strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients from 2020 to 2024, the review highlights how biomarkers like ctDNA and PD-L1 expression critically inform the selection of personalized therapies, particularly beneficial in the advanced stages of NSCLC. These biomarkers are critical for prognostic assessments and in dynamically adapting treatment plans, where high PD-L1 expression and specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide the use of targeted therapies and immunotherapies. The findings recommend integrating these biomarkers into standardized clinical pathways to maximize their potential in enhancing the treatment precision, ultimately fostering significant advancements in oncology and improving patient outcomes and quality of life. This review substantiates the prognostic and predictive value of these biomarkers and emphasizes the need for ongoing innovation in biomarker research.

Scientific Output by Latin American Women in Pediatric Surgical Sciences Over the Past 11 Years: A Bibliometric and Visual Analysis.

INTRODUCTION: This academic article discusses the historical underrepresentation of female in science, with a focus on Latin America. It highlights the importance of both technical and non-technical skills in the medical-surgical field, particularly the role of research skills. The study aims to quantify and characterize the scientific output of Latin American female researchers over the past decade, providing insights into the challenges and opportunities in low and middle-income countries. MATERIAL AND METHODS: A retrospective cross-sectional bibliometric study was conducted in 2023, focusing on pediatric surgical science journals in Scopus and PubMed. It assessed Latin American female participation, journal details, and interaction networks, using SPSS and Gephi software. The period analyzed was from January 2012 to December 2022. RESULTS: Between 2012 and 2022, 727 articles with Latin authorship in pediatric surgery were analyzed across 304 journals. Of these, 63.69% had female co-authors. The majority were original articles (53.13%), with contributions from Brazil, Mexico, and Chile. Notable journals included the Journal of Pediatric Surgery and Child's Nervous System. Keywords like Laparoscopy and Cardiac surgery were common. A growth trend in female Latin American publications was observed, despite temporary declines. CONCLUSIONS: This study highlights a growing trend in Latin American females' scientific contributions to pediatric surgery from 2012 to 2022, although a gender gap persists. The research mainly consists of primary data studies, with a focus on Brazil and Mexico from public institutions. The Journal of Pediatric Surgery featured prominently, and common topics included Laparoscopy, Cardiac surgery, Liver transplant, Congenital heart defects, and COVID-19. LEVEL OF EVIDENCE: IV.

Characterization and Classification In Silico of Peptides with Dual Activity (Antimicrobial and Wound Healing).

The growing challenge of chronic wounds and antibiotic resistance has spotlighted the potential of dual-function peptides (antimicrobial and wound healing) as novel therapeutic strategies. The investigation aimed to characterize and correlate in silico the physicochemical attributes of these peptides with their biological activity. We sourced a dataset of 207 such peptides from various peptide databases, followed by a detailed analysis of their physicochemical properties using bioinformatic tools. Utilizing statistical tools like clustering, correlation, and principal component analysis (PCA), patterns and relationships were discerned among these properties. Furthermore, we analyzed the peptides' functional domains for insights into their potential mechanisms of action. Our findings spotlight peptides in Cluster 2 as efficacious in wound healing, whereas Cluster 1 peptides exhibited pronounced antimicrobial potential. In our study, we identified specific amino acid patterns and peptide families associated with their biological activities, such as the cecropin antimicrobial domain. Additionally, we found the presence of polar amino acids like arginine, cysteine, and lysine, as well as apolar amino acids like glycine, isoleucine, and leucine. These characteristics are crucial for interactions with bacterial membranes and receptors involved in migration, proliferation, angiogenesis, and immunomodulation. While this study provides a groundwork for therapeutic development, translating these findings into practical applications necessitates additional experimental and clinical research.

CEA-delta could be a biomarker of tumor phenotype, clinical stage, and chemotherapeutic response in rectal cancer with OCT4-positive cancer stem cells.

Background: There is very limited evidence on biomarkers for evaluating the clinical behavior and therapeutic response in rectal cancer (RC) with positive expression of cancer stem cells (CSCs). Methods: An exploratory prospective study was conducted, which included fresh samples of tumor tissue from 109 patients diagnosed with primary RC. Sociodemographic, pathological and clinical characteristics were collected from medical records and survey. The OCT4 protein was isolated using the Western Blot technique. It was calculated the ΔCEA, ΔOCT4, and ΔOCT4/GUSB values by assessing the changes before and after chemotherapy, aiming to evaluate the therapeutic response. Results: Patients had an average age of 69.9 years, with 55% (n=60) being male. Approximately 63.3% of the tumors were undifferentiated, and the most frequent staging classification was pathological stage III (n=64; 58.7%). Initial positive expression was observed in 77.1% of the patients (n=84), and the median ΔCEA was -1.03 (-3.82 - 0.84) ng/ml, with elevated levels (< -0.94 ng/ml) found in 51.4% of the subjects (n=56). Being OCT4 positive and having an elevated ΔCEA value were significantly associated with undifferentiated tumor phenotype (p=0.002), advanced tumor progression stage (p <0.001), and negative values of ΔOCT4 (p <0.001) (suggestive of poor therapeutic response) compared to those without this status. Conclusion: This study identified a significant and directly proportional association among the values of ΔCEA, ΔOCT4, and ΔOCT4/GUSB. These findings suggest that ΔCEA holds potential as a clinical biomarker for determining the undifferentiated tumor phenotype, advanced clinical stage, and poor therapeutic response in RC with CSCs positive expression.

High OCT4 Expression Might Be Associated with an Aggressive Phenotype in Rectal Cancer.

Rectal cancer (RC) is one of the most common malignant neoplasms, and cancer stem cells (CSCs) of the intestinal tract have been implicated in its origin. The oncofetal protein OCT4 has been linked to neoplastic processes, but its role and clinical significance in RC are unknown. This study investigates the expression of the stem cell marker OCT4 related to clinical-pathological characteristics and its clinical significance in RC patients. The expression level of stem cell marker OCT4 was analyzed in 22 primary rectal tumors by western blot. The association between OCT4 protein expression and the clinical-pathological features of tumors was evaluated by χ2 test and Fisher's exact test. We demonstrated that the expression of the stem cell marker OCT4 was observed in tumor tissue but not adjacent non-tumor tissue. High expression of the stem cell marker OCT4 was significantly associated with histological differentiation grade (p = 0.039), tumor invasion level (p = 0.004), lymph node involvement (p = 0.044), tumor-node-metastasis (TNM) stage (p = 0.002), and clinical stage (p = 0.021). These findings suggest that high OCT4 expression is associated with a more aggressive RC phenotype, with a greater likelihood of progression and metastasis. These results shed light on the importance of targeting this CSC marker to attenuate RC progression.

Advances in Genomic Data and Biomarkers: Revolutionizing NSCLC Diagnosis and Treatment.

Non-small cell lung cancer (NSCLC) is a significant public health concern with high mortality rates. Recent advancements in genomic data, bioinformatics tools, and the utilization of biomarkers have improved the possibilities for early diagnosis, effective treatment, and follow-up in NSCLC. Biomarkers play a crucial role in precision medicine by providing measurable indicators of disease characteristics, enabling tailored treatment strategies. The integration of big data and artificial intelligence (AI) further enhances the potential for personalized medicine through advanced biomarker analysis. However, challenges remain in the impact of new biomarkers on mortality and treatment efficacy due to limited evidence. Data analysis, interpretation, and the adoption of precision medicine approaches in clinical practice pose additional challenges and emphasize the integration of biomarkers with advanced technologies such as genomic data analysis and artificial intelligence (AI), which enhance the potential of precision medicine in NSCLC. Despite these obstacles, the integration of biomarkers into precision medicine has shown promising results in NSCLC, improving patient outcomes and enabling targeted therapies. Continued research and advancements in biomarker discovery, utilization, and evidence generation are necessary to overcome these challenges and further enhance the efficacy of precision medicine. Addressing these obstacles will contribute to the continued improvement of patient outcomes in non-small cell lung cancer.

In Vitro Evaluation of the Potential Pharmacological Activity and Molecular Targets of New Benzimidazole-Based Schiff Base Metal Complexes.

Metal-based drugs, including lanthanide complexes, have been extremely effective in clinical treatments against various diseases and have raised major interest in recent decades. Hence, in this work, a series of lanthanum (III) and cerium (III) complexes, including Schiff base ligands derived from (1H-benzimidazol-2-yl)aniline, salicylaldehyde, and 2,4-dihydroxybenzaldehyde were synthesized and characterized using different spectroscopic methods. Besides their cytotoxic activities, they were examined in human U-937 cells, primate kidney non-cancerous COS-7, and six other, different human tumor cell lines: U251, PC-3, K562, HCT-15, MCF-7, and SK-LU-1. In addition, the synthesized compounds were screened for in vitro antiparasitic activity against Leishmania braziliensis, Plasmodium falciparum, and Trypanosoma cruzi. Additionally, antibacterial activities were examined against two Gram-positive strains (S. aureus ATCC® 25923, L. monocytogenes ATCC® 19115) and two Gram-negative strains (E. coli ATCC® 25922, P. aeruginosa ATCC® 27583) using the microdilution method. The lanthanide complexes generally exhibited increased biological activity compared with the free Schiff base ligands. Interactions between the tested compounds and model membranes were examined using differential scanning calorimetry (DSC), and interactions with calf thymus DNA (CT-DNA) were investigated by ultraviolet (UV) absorption. Molecular docking studies were performed using leishmanin (1LML), cruzain (4PI3), P. falciparum alpha-tubulin (GenBank sequence CAA34101 [453 aa]), and S.aureus penicillin-binding protein 2a (PBP2A; 5M18) as the protein receptors. The results lead to the conclusion that the synthesized compounds exhibited a notable effect on model membranes imitating mammalian and bacterial membranes and rolled along DNA strands through groove interactions. Interactions between the compounds and studied receptors depended primarily on ligand structures in the molecular docking study.

In Silico Selection and Evaluation of Pugnins with Antibacterial and Anticancer Activity Using Skin Transcriptome of Treefrog (Boana pugnax).

In order to combat bacterial and cancer resistance, we identified peptides (pugnins) with dual antibacterial l-anticancer activity from the Boana pugnax (B. pugnax) skin transcriptome through in silico analysis. Pugnins A and B were selected owing to their high similarity to the DS4.3 peptide, which served as a template for their alignment to the B. pugnax transcriptome, as well as their function as part of a voltage-dependent potassium channel protein. The secondary peptide structure stability in aqueous medium was evaluated as well, and after interaction with the Escherichia coli (E. coli) membrane model using molecular dynamics. These pugnins were synthesized via solid-phase synthesis strategy and verified by Reverse phase high-performance liquid chromatography (RP-HPLC) and mass spectrometry. Subsequently, their alpha-helix structure was determined by circular dichroism, after which antibacterial tests were then performed to evaluate their antimicrobial activity. Cytotoxicity tests against cancer cells also showed selectivity of pugnin A toward breast cancer (MFC7) cells, and pugnin B toward prostate cancer (PC3) cells. Alternatively, flow cytometry revealed necrotic cell damage with a major cytotoxic effect on human keratinocytes (HaCaT) control cells. Therefore, the pugnins found in the transcriptome of B. pugnax present dual antibacterial-anticancer activity with reduced selectivity to normal eukaryotic cells.

Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking.

Multidrug resistance to chemotherapy is a critical health problem associated with mutation of the therapeutic target. Therefore, the development of anticancer agents remains a challenge to overcome cancer cell resistance. Herein, a new series of quinazoline-based pyrimidodiazepines 16a-g were synthesized by the cyclocondensation reaction of 2-chloro-4-anilinoquinazoline-chalcones 14a-g with 2,4,5,6-tetraaminopyrimidine. All quinazoline derivatives 14a-g and 16a-g were selected by the U.S. National Cancer Institute (NCI) for testing their anticancer activity against 60 cancer cell lines of different panels of human tumors. Among the tested compounds, quinazoline-chalcone 14g displayed high antiproliferative activity with GI50 values between 0.622-1.81 µM against K-562 (leukemia), RPMI-8226 (leukemia), HCT-116 (colon cancer) LOX IMVI (melanoma), and MCF7 (breast cancer) cancer cell lines. Additionally, the pyrimidodiazepines 16a and 16c exhibited high cytostatic (TGI) and cytotoxic activity (LC50), where 16c showed high cytotoxic activity, which was 10.0-fold higher than the standard anticancer agent adriamycin/doxorubicin against ten cancer cell lines. COMPARE analysis revealed that 16c may possess a mechanism of action through DNA binding that is similar to that of CCNU (lomustine). DNA binding studies indicated that 14g and 16c interact with the calf thymus DNA by intercalation and groove binding, respectively. Compounds 14g, 16c and 16a displayed strong binding affinities to DNA, EGFR and VEGFR-2 receptors. None of the active compounds showed cytotoxicity against human red blood cells.

In Silico Discovery of Antimicrobial Peptides as an Alternative to Control SARS-CoV-2.

A serious pandemic has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The interaction between spike surface viral protein (Sgp) and the angiotensin-converting enzyme 2 (ACE2) cellular receptor is essential to understand the SARS-CoV-2 infectivity and pathogenicity. Currently, no drugs are available to treat the infection caused by this coronavirus and the use of antimicrobial peptides (AMPs) may be a promising alternative therapeutic strategy to control SARS-CoV-2. In this study, we investigated the in silico interaction of AMPs with viral structural proteins and host cell receptors. We screened the antimicrobial peptide database (APD3) and selected 15 peptides based on their physicochemical and antiviral properties. The interactions of AMPs with Sgp and ACE2 were performed by docking analysis. The results revealed that two amphibian AMPs, caerin 1.6 and caerin 1.10, had the highest affinity for Sgp proteins while interaction with the ACE2 receptor was reduced. The effective AMPs interacted particularly with Arg995 located in the S2 subunits of Sgp, which is key subunit that plays an essential role in viral fusion and entry into the host cell through ACE2. Given these computational findings, new potentially effective AMPs with antiviral properties for SARS-CoV-2 were identified, but they need experimental validation for their therapeutic effectiveness.

Peptides with Dual Antimicrobial-Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides.

Peptides are naturally produced by all organisms and exhibit a wide range of physiological, immunomodulatory, and wound healing functions. Furthermore, they can provide with protection against microorganisms and tumor cells. Their multifaceted performance, high selectivity, and reduced toxicity have positioned them as effective therapeutic agents, representing a positive economic impact for pharmaceutical companies. Currently, efforts have been made to invest in the development of new peptides with antimicrobial and anticancer properties, but the poor stability of these molecules in physiological environments has triggered a bottleneck. Therefore, some tools, such as nanotechnology and in silico approaches can be applied as alternatives to try to overcome these obstacles. In silico studies provide a priori knowledge that can lead to the development of new anticancer peptides with enhanced biological activity and improved stability. This review focuses on the current status of research in peptides with dual antimicrobial-anticancer activity, including advances in computational biology using in silico analyses as a powerful tool for the study and rational design of these types of peptides.