Browsing by Author "Liscano, Yamil"
Now showing 1 - 20 of 28
Results Per Page
Sort Options
Item A Vitiligo-like Cutaneous Reaction Induced by Ribociclib in Advanced Breast Cancer: An Unusual Case Report from Colombia(Multidisciplinary Digital Publishing Institute (MDPI), 2025-05-19) Montenegro, John Fernando; Rivas Tafurt, Giovanna Patricia; Vidal Cañas, Sinthia; Diaz Diaz, Miguel Ángel; Bermudez, Cesar Eduardo; Florez, Daniel; Bravo Gustin, Andres Felipe; Liscano, YamilBackground: Cutaneous toxicities associated with CDK4/6 inhibitors are uncommon but may affect treatment adherence. We present the case of a patient with advanced breast cancer who developed vitiligo-like lesions after initiating ribociclib, contributing to the growing evidence of this under-recognized adverse effect. Methods: We present the case of a 72-year-old woman diagnosed in 2007 with early-stage, luminal A, HER2-negative breast cancer, initially treated with surgery and tamoxifen. In 2022, she experienced locoregional recurrence with bone metastases. In January 2023, she began treatment with ribociclib plus letrozole. Two months later, she developed intense pruritus, xerosis, and paresthesia, followed by hypopigmented lesions on her face and upper extremities. Clinical evaluation, supported by photographs and a skin biopsy (led to a diagnosis of ribociclib-induced vitiligo. Management included dose adjustments to the ribociclib and dermatologic treatments, including topical corticosteroids, antihistamines, and short courses of oral prednisone. Results: By September 2024, her skin lesions had stabilized and her pruritus improved with a reduced dose of ribociclib (one tablet per day). However, the hypopigmented patches persisted, mainly on her face and extremities. Despite these cutaneous effects, she maintained an acceptable quality of life and continued effective oncologic treatment.Item Actinomycosis: Mimicking Malignancies in Multiple Anatomical Sites—A Three-Patient Case Series(Multidisciplinary Digital Publishing Institute (MDPI), 2025-02-02) Montenegro, John Fernando; Correa Forero, Vanessa; Liscano, Yamil; Grueso Pineda, Andres; Bonilla Bonilla, Diana Marcela; Ruiz Jimenez, Paola AndreaBackground and Objectives: Actinomycosis is a rare chronic contagion caused by Actinomyces spp. known for its ability to mimic malignant processes across various anatomical locations. Its clinical presentation can often resemble malignancies, Mycobacterium tuberculosis infections, nocardiosis, fungal infections, or other granulomatous diseases. This case series presents three patients diagnosed with Actinomyces spp., highlighting the diagnostic challenges and diverse clinical manifestations of the disease. Materials and Methods: We reviewed the clinical course, diagnostic procedures, and treatment outcomes of three patients with confirmed Actinomyces spp. The first case involved a 51-year-old male with a history of rhabdomyosarcoma in remission who presented with dysphagia. Magnetic resonance imaging identified an irregularly enhancing mass in the tonsil, and subsequent tonsillectomy confirmed Actinomyces spp. The second patient, an 80-year-old female, presented with dysphagia and a sublingual mass initially suspected to be diffuse large B-cell non-Hodgkin lymphoma; however, a histopathological analysis confirmed Actinomyces spp. The third case involved a 72-year-old male with abdominal pain and an ulcerated gastric lesion, where subtotal gastrectomy and histopathological examination confirmed the diagnosis of Actinomyces spp. Results: These three cases highlight the ability of Actinomyces spp. to closely mimic malignant lesions, which significantly complicates the diagnostic process. Although personalized interventions were required for each patient, diagnoses were ultimately confirmed through histopathology. Despite these challenges, timely recognition and appropriate treatment were achieved, underscoring the need to consider Actinomyces spp. in the differential diagnosis of similar presentations. Conclusions: Actinomyces spp. remains a diagnostic challenge due to its ability to mimic a variety of malignant and contagion conditions. This case series emphasizes the need for a thorough histopathological examination and a high index of suspicion when encountering lesions with atypical presentations. Given the potential for misdiagnosis, awareness and consideration of Actinomyces spp. are crucial in the differential diagnosis of chronic contagion and mass lesions. Further studies are warranted to refine diagnostic and therapeutic approaches.Item Antibacterial activity and molecular studies of non-symmetric POCOP-Pd(II) pincer complexes derived from 2,4-dihydroxybenzaldehyde (2,4-DHBA)(2022-11-15) Aragón Muriel, Alberto; Aguilar Castillo, Bethsy A.; Rufino Felipe, Ernesto; Valdés, Hugo; González Sebastián, Lucero; Osorio Yáñez, Rebeca Nayely; Liscano, Yamil; Gómez Benítez, Valente; Polo Cerón, Dorian; Morales Morales, DavidA series of non-symmetric POCOP-Pd(II) pincer complexes including an aldehyde group in the meta-position of the aromatic pincer-backbone were prepared and characterized. The molecular structure of complex 1-Pd was unambiguously determined by single crystal X-ray diffraction analysis, showing a square-planar geometry around the metal fragment and the presence of the aldehyde functionality at the pincer ligand backbone. The evaluation of the antibacterial activities of complexes 2-Pd and 3-Pd against gram-positive and gram-negative strains was performed. Complex 3-Pd was the most active against S. aureus ATCC 25923 strain with a MIC value of 8 µg∙mL−1. We also determined by molecular docking studies, that pincer complexes 2-Pd and 3-Pd may interact with some key bacterial enzymes such as KPC-2 and PBP2A.Item Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking(2021) Cuartas, Viviana; Aragón Muriel, Alberto; Liscano, Yamil; Polo Cerón, Dorian; Crespo Ortiz, Maria del Pilar; Quiroga, Jairo; Abonia, Rodrigo; Insuasty, BraulioMultidrug 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 pyrimidodiazepines16a-gwere synthesized by the cyclocondensation reaction of 2-chloro-4-anilinoquinazoline-chalcones14a-gwith 2,4,5,6-tetraaminopyrimidine. All quinazoline derivatives14a-gand16a-gwere 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-chalcone14gdisplayed high antiproliferative activity with GI50values 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 pyrimidodiazepines16aand16cexhibited high cytostatic (TGI) and cytotoxic activity (LC50), where16cshowed high cytotoxic activity, which was 10.0-fold higher than the standard anticancer agent adriamycin/doxorubicin against ten cancer cell lines. COMPARE analysis revealed that16cmay possess a mechanism of action through DNA binding that is similar to that of CCNU (lomustine). DNA binding studies indicated that14gand16cinteract with the calf thymus DNA by intercalation and groove binding, respectively. Compounds14g,16cand16adisplayed strong binding affinities to DNA, EGFR and VEGFR-2 receptors. None of the active compounds showed cytotoxicity against human red blood cells.Item Antimicrobial contribution of chitosan surface-modified nanoliposomes combined with colistin against sensitive and colistin-resistant clinical Pseudomonas aeruginosa(2021) Laverde Rojas, Valentina; Liscano, Yamil; Rivera Sánchez, Sandra Patricia; Ocampo Ibáñez, Ivan Darío; Betancourt, Yeiston; Alhajj, Maria José; Yarce, Cristhian J.; Salamanca, Constain H.; Oñate Garzón, JoseColistin is a re-emergent antibiotic peptide used as a last resort in clinical practice to overcome multi-drug resistant (MDR) Gram-negative bacterial infections. Unfortunately, the dissemination of colistin-resistant strains has increased in recent years and is considered a public health problem worldwide. Strategies to reduce resistance to antibiotics such as nanotechnology have been applied successfully. In this work, colistin was characterized physicochemically by surface tension measurements. Subsequently, nanoliposomes coated with highly deacetylated chitosan were prepared with and without colistin. The nanoliposomes were characterized using dynamic light scattering and zeta potential measurements. Both physicochemical parameters fluctuated relatively to the addition of colistin and/or polymer. The antimicrobial activity of formulations increased by four-fold against clinical isolates of susceptible Pseudomona aeruginosa but did not have antimicrobial activity against multidrug-resistant (MDR) bacteria. Interestingly, the free coated nanoliposomes exhibited the same antibacterial activity in both sensitive and MDR strains. Finally, the interaction of colistin with phospholipids was characterized using molecular dynamics (MD) simulations and determined that colistin is weakly associated with micelles constituted by zwitterionic phospholipidsItem Association of CETP, APOA5, IL6, and PON1 Gene Variants with Dyslipidemia and Cardiovascular Risk in a Population from Cauca Department, Colombia(Multidisciplinary Digital Publishing Institute (MDPI), 2025-04-30) Urbano Cano, Astrid Lorena; Álvarez Rosero, Rosa Elvira; Liscano, YamilBackground: Cardiovascular disease remains the leading cause of death worldwide, and dyslipidemia is a critical, modifiable risk factor. Aim: We sought to evaluate the relationship between polymorphisms in CETP (rs3764261), APOA5 (rs662799), IL6 (rs1800796), and PON1 (Q192R) and lipid parameters, and to assess their contribution to dyslipidemia and overall cardiovascular risk in an urban cohort from Cauca, Colombia. Methods: In this cross-sectional observational study, 304 participants aged 40–69 years were enrolled. Clinical, anthropometric, and biochemical data were collected, and genotyping was performed for the four target polymorphisms. We used descriptive statistics to characterize the sample, non-parametric tests to compare lipid levels by genotype, and multivariable logistic regression to identify independent predictors of dyslipidemia. Results: Individuals with dyslipidemia exhibited significantly higher total cholesterol and VLDL levels, lower HDL levels, and an elevated Castelli II index compared with the non-dyslipidemia group. Although CETP genotype frequencies differed between groups, only the APOA5 rs662799 variant was significantly associated with increased VLDL levels, suggesting its potential role as a genetic biomarker of cardiovascular risk.Item Bilateral Congenital Knee Dislocation in Colombia: Case Report and Literature Review(Multidisciplinary Digital Publishing Institute (MDPI), 2023-01) Salguero Sánchez, Jefferson Augusto; Sánchez Duque, Santiago Andrés; Lozada Martínez, Ivan David; Liscano, Yamil; Díaz Vallejo, Jhony AlejandroCongenital knee dislocation (CKD) is a rare disease with an estimated incidence of 1 per 100,000 live births, characterized by a rare musculoskeletal malformation in genu recurvatum deformity present at birth, affecting one or both lower limbs. The diagnosis may be suspected during ultrasound when observing that the situation of the extremities is not correct, and is confirmed by physical examination at birth, with plain radiography being helpful to establish the degree of severity. At present there are controversies regarding treatment and there is no definitive protocol. We present a new case of CKD, observed in the city of Manizales, diagnosed immediately after birth.Item Biopolymers as a Potential Alternative for the Retention of Pollutants from Vinasse: An In Silico Approach(MDPI, 2024) Aristizabal, Yesid; Ciro, Yhors; Liscano, Yamil; Salamanca, Constain H.; Oñate Garzón, JoseVinasse, a waste from the bioethanol industry, presents a crucial environmental challenge due to its high organic matter content, which is difficult to biodegrade. Currently, no sustainable alternatives are available for treating the amount of vinasse generated. Conversely, biopolymers such as cellulose, carboxymethylcellulose, and chitosan are emerging as an interesting alternative for vinasse control due to their flocculating capacity against several organic compounds. This study seeks to determine the thermodynamic behavior of in silico interactions among three biopolymers (cellulose, carboxymethylcellulose, and chitosan) regarding 15 organic compounds found in vinasse. For this, the Particle Mesh Ewald (PME) method was used in association with the Verlet cutoff scheme, wherein the Gibbs free energy (ΔG) was calculated over a 50 ns simulation period. The findings revealed that cellulose showed a strong affinity for flavonoids like cyanidin, with a maximum free energy of −84 kJ/mol and a minimum of −55 kJ/mol observed with phenolic acids and other flavonoids. In contrast, chitosan displayed the highest interactions with phenolic acids, such as gallic acid, reaching −590 kJ/mol. However, with 3-methoxy-4-hydroxyphenyl glycol (MHPG), it reached an energy of −70 kJ/mol. The interaction energy for flavonoid ranged from −105 to −96 kJ/mol. Finally, carboxymethylcellulose (CMC) demonstrated an interaction energy with isoquercetin of −238 kJ/mol, while interactions with other flavonoids were almost negligible. Alternatively, CMC exhibited an interaction energy of −124 kJ/mol with MHPG, while it was less favorable with other phenolic acids with minimal interactions. These results suggest that there are favorable interactions for the interfacial sorption of vinasse contaminants onto biopolymers, indicating their potential for use in the removal of contaminants from the effluents of the bioethanol industry.Item CEA-delta could be a biomarker of tumor phenotype, clinical stage, and chemotherapeutic response in rectal cancer with OCT4-positive cancer stem cells(Frontiers Media SA, 2023) Lozada Martinez, Ivan David; Bolaño Romero, Maria Paz; Lambis Anaya, Lina; Liscano, Yamil; Suarez Causado, AmilethBackground: 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.Item Characterization and Classification In Silico of Peptides with Dual Activity (Antimicrobial and Wound Healing)(2023-09) Trejos, María; Aristizabal, Yesid; Aragón Muriel, Alberto; Oñate Garzón, José; Liscano, YamilThe 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.Item Design, Synthesis and Antimicrobial Potential of Conjugated Metallopeptides Targeting DNA(MDPI, 2024) Moreno Ramirez, Maria Camila; Arias Bravo, Adriana Stefania; Aragón Muriel, Alberto; Godoy, César Alonso; Liscano, Yamil; Oñate Garzón, Jose; Polo Cerón, DorianAntimicrobial resistance threatens the effective prevention and treatment of an increasingly broad spectrum of infections caused by pathogenic microorganisms. This pressing challenge has intensified the search for alternative antibiotics with new pharmacological properties. Due to the chemical synergy between the biological activity of antimicrobial peptides (AMPs) and the different modes of action, catalytic properties, and redox chemistry of metal complexes, metallopeptides have emerged in recent years as an alternative to conventional antibiotics. In the present investigation, peptide ligands conjugated with 5-carboxy-1,10-phenanthroline (Phen) were prepared by solid-phase peptide synthesis (SPPS), and the corresponding copper(II) metallopeptides, Cu-PhenKG and Cu-PhenRG (where K = lysine, R = arginine, and G = glycine), were synthesized and characterized. The antimicrobial activities of these compounds toward Gram-positive and Gram-negative bacteria, evaluated by the broth microdilution technique, indicate that the metal center in the metallopeptides increases the antimicrobial activity of the complexes against the conjugated peptide ligands. Minimum inhibitory concentration (MIC) values of 0.5 μg/mL for S. aureus with the Cu-PhenKG complex and 0.63 μg/mL for S. typhimurium with the Cu-PhenRG complex were obtained. The MIC values found for the conjugated peptides in all microorganisms tested were greater than 1.5 μg/mL. The interactions of the conjugated peptides and their metallopeptides with plasmid DNA were evaluated by agarose gel electrophoresis. Alterations on the replication machinery were also studied by polymerase chain reaction (PCR). The results indicate that the complexes interact efficiently with pBR322 DNA from E. coli, delaying the band shift. Furthermore, the resulting DNA–metallopeptide complex is not a useful template DNA because it inhibits PCR, since no PCR product was detected. Finally, molecular dynamics and molecular docking simulations were performed to better understand the interactions of the obtained compounds with DNA. The Cu-PhenRG complex shows a significantly higher number of polar interactions with DNA, suggesting a higher binding affinity with the biopolymer.Item Diabetic Ketoacidosis as a Debut and Immune-Mediated Complication Caused by Pembrolizumab: Case Report(MDPI, 2024) Pacichana, Julian Andrés; Osorio, Luis Miguel; Restrepo, Katherine; García, Andres Felipe; Rivas, Giovanna; Liscano, YamilBackground/Objectives: Diabetic ketoacidosis (DKA) is an acute and potentially life-threatening complication characterized by the accumulation of ketone bodies in the blood, primarily occurring in patients with type 1 diabetes and occasionally in those with type 2 diabetes under certain conditions. DKA presents with symptoms such as polyuria, polydipsia, polyphagia, and, in severe cases, mental status changes. Identifying the triggering factor is crucial to prevent complications and effectively manage this medical emergency. Methods: This report describes the case of a 58-year-old male patient with stage IIIb nodular melanoma, diagnosed in November 2022. Results: After receiving five cycles of pembrolizumab, the patient developed de novo DKA, presenting with blurred vision, asthenia, adynamia, polyuria, and polydipsia. He was admitted to the emergency department with a blood glucose level of 764 mg/dL, confirming hyperglycemia and metabolic acidosis. He was transferred to the intensive care unit for fluid resuscitation and insulin infusion. After adequate clinical evolution and meeting the criteria for DKA resolution, possible autoimmune endocrinopathies secondary to immunotherapy were considered. Due to this complication, the oncological treatment was changed. Finally, the patient was discharged with the need to continue insulin therapy and oral hypoglycemic agents, along with thyroid hormone supplementation. Conclusions: The novelty of this case lies in the presentation of DKA as an immune-mediated complication induced by pembrolizumab, highlighting the importance of closely monitoring patients receiving immune checkpoint inhibitors to detect and manage emerging autoimmune endocrinopathies. It is essential to adjust oncological treatment according to the patient’s response and promptly manage autoimmune endocrinopathies to improve clinical outcomes and the patient’s quality of life.Item Electroencephalography-Based Brain-Computer Interfaces in Rehabilitation: A Bibliometric Analysis (2013–2023)(MDPI, 2024) Angulo Medina, Ana Sophia; Aguilar Bonilla, Maria Isabel; Rodríguez Giraldo, Ingrid Daniela; Montenegro Palacios, John Fernando; Cáceres Gutiérrez, Danilo Andrés; Liscano, YamilEEG-based Brain-Computer Interfaces (BCIs) have gained significant attention in rehabilitation due to their non-invasive, accessible ability to capture brain activity and restore neurological functions in patients with conditions such as stroke and spinal cord injuries. This study offers a comprehensive bibliometric analysis of global EEG-based BCI research in rehabilitation from 2013 to 2023. It focuses on primary research and review articles addressing technological innovations, effectiveness, and system advancements in clinical rehabilitation. Data were sourced from databases like Web of Science, and bibliometric tools (bibliometrix R) were used to analyze publication trends, geographic distribution, keyword co-occurrences, and collaboration networks. The results reveal a rapid increase in EEG-BCI research, peaking in 2022, with a primary focus on motor and sensory rehabilitation. EEG remains the most commonly used method, with significant contributions from Asia, Europe, and North America. Additionally, there is growing interest in applying BCIs to mental health, as well as integrating artificial intelligence (AI), particularly machine learning, to enhance system accuracy and adaptability. However, challenges remain, such as system inefficiencies and slow learning curves. These could be addressed by incorporating multi-modal approaches and advanced neuroimaging technologies. Further research is needed to validate the applicability of EEG-BCI advancements in both cognitive and motor rehabilitation, especially considering the high global prevalence of cerebrovascular diseases. To advance the field, expanding global participation, particularly in underrepresented regions like Latin America, is essential. Improving system efficiency through multi-modal approaches and AI integration is also critical. Ethical considerations, including data privacy, transparency, and equitable access to BCI technologies, must be prioritized to ensure the inclusive development and use of these technologies across diverse socioeconomic groups.Item High OCT4 Expression Might Be Associated with an Aggressive Phenotype in Rectal Cancer(2023-07) Lambis Anaya, Lina; Fernández Ruiz, Mashiel; Liscano, Yamil; Suarez Causado, AmilethRectal 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.Item Impact of Central Line-Associated Bloodstream Infections on Mortality and Hospital Stay in Adult Patients at a Tertiary Care Institution in Cali, Colombia, 2015–2018(American Institute of Physics, 2024) Mosquera, Jorge Mario Angulo; Assis Reveiz, Jorge Karim; Barrera, Lena; Liscano, YamilBackground: Central line-associated bloodstream infections (CLABSIs) are a significant healthcare challenge globally, increasing mortality risk and complicating central vascular catheter use. In Colombia, few studies have assessed the impact of CLABSIs on hospital stay and mortality. Objective: To determine the association between CLABSIs and discharge outcomes and hospital stay duration in adult patients at a tertiary care institution in Cali, Colombia, from 1 January 2015 to 31 December 2018. Methods: A nested case–control study was conducted. The odds of mortality associated with CLABSIs were estimated using conditional logistic regression. Non-conditional logistic regression was used to determine the odds of mortality when CLABSIs were caused by resistant microorganisms. Hospital stay duration, catheter duration, and time from catheter insertion to discharge were compared between patients with and without CLABSIs. The most frequent etiological agents were identified. Results: Patients with CLABSIs had 3.89 times the odds of mortality (95% CI [1.33–11.31], p = 0.013) compared to those without CLABSIs. The odds of mortality for patients with resistant microorganism CLABSIs were 4.04 times (95% CI [1.17–13.96], p = 0.027) higher than those with sensitive microorganism CLABSIs. Hospital stay duration (median = 51 days vs. 17 days; p = 0.000), catheter duration (median = 19 days vs. 7 days; p < 0.001), and time from catheter insertion to discharge (median = 40 days vs. 9 days; p < 0.001) were significantly longer in CLABSI patients. Klebsiella pneumoniae was the most isolated pathogen (20.2%), followed by Staphylococcus aureus (14.9%). Implications: CLABSI patients have longer catheter and hospitalization durations and higher mortality risk. Resistant microorganism CLABSIs are associated with elevated mortality risk. Conclusions: This study corroborates the positive relation between CLABSI and the mortality risk, which is influenced by resistant bacteria, though causality is not established. CLABSI is also linked to longer hospital stays, underscoring the need for improving infection control strategies.Item In silico characterization of the interaction between the pbp2a “decoy” protein of resistant staphylococcus aureus and the monomeric units of eudragit e-100 and poly(Maleic acid-alt-octadecene) polymers(2021) Liscano, Yamil; Amú, Ana; González, Astrid; Oñate Garzón, Jose; Salamanca, Constain H.Antimicrobial treatment alternatives for methicillin-resistant Staphylococcus aureus (MRSA) are increasingly limited. MRSA strains are resistant to methicillin due to the formation of β-lactamase enzymes, as well as the acquisition of the mecA gene, which encodes the penicillin-binding protein (PBP2a) that reduces the affinity for β-lactam drugs. Previous studies have shown that the use of ampicillin-loaded nanoparticles can improve antimicrobial activity on resistant S. aureus strains. However, the biological mechanism of this effect has not yet been properly elucidated. Therefore, this short communication focused on characterizing the in silico interactions of the PBP2a membrane receptor protein from S. aureus against the monomeric units of two polymeric materials previously used in the development of different nanoparticles loaded with ampicillin. Such polymers correspond to Eudragit E-100 chloride (EuCl) and the sodium salt of poly(maleic acid-alt-octadecene) (PAM-18Na). For this, molecular coupling studies were carried out in the active site of the PBP2a protein with the monomeric units of both polymers in neutral and ionized form, as well as with ampicillin antibiotic (model β-lactam drug). The results showed that ampicillin, as well as the monomeric units of EuCl and PAM18Na, described a slight binding free energy to the PBPa2 protein. In addition, it was found that the amino acids of the active site of the PBPa2 protein have interactions of different types and intensities, suggesting, in turn, different forms of protein–substrate coupling.Item In silico selection and evaluation of pugnins with antibacterial and anticancer activity using skin transcriptome of treefrog (Boana pugnax)(2021) Liscano, Yamil; Medina, Laura; Oñate-Garzón, Jose; Gúzman, Fanny; Pickholz, Monica; Delgado, Jean PaulIn 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 cellsItem In vitro evaluation of the potential pharmacological activity and molecular targets of new benzimidazole-based schiff base metal complexes(2021) Aragón Muriel, Alberto; Liscano, Yamil; Upegui, Yulieth; Robledo, Sara M.; Ramírez-Apan, María Teresa; Morales Morales, David; Oñate Garzón, Jose; Polo Cerón, DorianMetal-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.Item Increases in hydrophilicity and charge on the polar face of alyteserin 1c helix change its selectivity towards gram-positive bacteria(MDPI AG, 2019-11-27) Liscano, Yamil; Salamanca, Constain H.; Vargas, Lina; Cantor, Stefania; Laverde Rojas, Valentina; Oñate Garzón, JoséRecently, resistance of pathogens towards conventional antibiotics has increased, representing a threat to public health globally. As part of the fight against this, studies on alternative antibiotics such as antimicrobial peptides have been performed, and it has been shown that their sequence and structure are closely related to their antimicrobial activity. Against this background, we here evaluated the antibacterial activity of two peptides developed by solid-phase synthesis, Alyteserin 1c (WT) and its mutant derivative (ΔM), which shows increased net charge and reduced hydrophobicity. These structural characteristics were modified as a result of amino acid substitutions on the polar face of the WT helix. The minimum inhibitory concentration (MIC) of both peptides was obtained in Gram-positive and Gram-negative bacteria. The results showed that the rational substitutions of the amino acids increased the activity in Gram-positive bacteria, especially against Staphylococcus aureus, for which the MIC was one-third of that for the WT analog. In contrast to the case for Gram-positive bacteria, these substitutions decreased activity against Gram-negative bacteria, especially in Escherichia coli, for which the MIC was eight-fold higher than that exhibited by the WT peptide. To understand this, models of the peptide behavior upon interacting with membranes of E. coli and S. aureus created using molecular dynamics were studied and it was determined that the helical stability of the peptide is indispensable for antimicrobial activity. The hydrogen bonds between the His20 of the peptides and the phospholipids of the membranes should modulate the selectivity associated with structural stability at the carboxy-terminal region of the peptides.Item Integrating In Vitro and In Silico Analysis of a Cationic Antimicrobial Peptide Interaction with Model Membranes of Colistin-Resistant Pseudomonas aeruginosa Strains(MDPI, 2022-06) Rivera Sanchez, Sandra Patricia; Ocampo Ibáñez, Iván Darío; Liscano, Yamil; Martínez, Natalia; Muñoz, Isamar; Manrique Moreno, Marcela; Martinez Martinez, Luis; Oñate Garzon, JoséBacterial antibiotic resistance is a serious global public health concern. Infections caused by colistin-resistant Pseudomonas aeruginosa (CRPa) strains represent a serious threat due to their considerable morbidity and mortality rates, since most of the current empirical antibiotic therapies are ineffective against these strains. Accordingly, cationic antimicrobial peptides (CAMPs) have emerged as promising alternatives to control resistant bacteria. In this study, the interaction of a CAMP derived from cecropin D-like (∆M2) with model membranes mimicking bacterial biomembranes of wild-type (WTPa) strains of P. aeruginosa and CRPa was evaluated through in vitro and in silico approaches. In vitro interaction was determined by infrared spectroscopy, whereas in silico molecular dynamics was performed to predict specific interactions between amino acids of ∆M2 and lipids of model membrane systems. Experimental analysis showed this peptide interacted with the lipids of bacteriallike model membranes of WTPa and CRPa. In both cases, an increase in the concentration of peptides induced an increase in the phase transition temperature of the lipid systems. On the other hand, the peptides in solution underwent a transition from a random to a helical secondary structure after interacting with the membranes mostly favored in the CRPa system. The α-helix structure percentage for ∆M2 interacting with WTPa and CRPa lipid systems was 6.4 and 33.2%, respectively. Finally, molecular dynamics showed ∆M2 to have the most affinities toward the phospholipids palmitoyl-oleyl-phosphatidylglycerol (POPG) and palmitoyl-oleoyl-phosphatidylethanolamine (POPE) that mimic membranes of WTPa and CRPa, respectively. This work provides clues for elucidating the membrane-associated mechanism of action of ∆M2 against colistin-susceptible and-resistant strains of Pseudomonas aeruginosa.