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Goyzueta-Mamani, L. D.

Publications and source records attributed to Goyzueta-Mamani, L. D..

4 recordsLinked to original sources

Thermorheological mapping and molecular insights into salt-dependent gel-like network formation in Mortierella alpina chitin-like exopolysaccharide solutions

Fungal chitin-like exopolysaccharides are promising fermentation-derived materials, however the molecular-level determinants of their salt- and temperature-dependent gel-like behavior remain poorly understood. Here, a previously characterized Mortierella alpina exopolysaccharide was re-examined by integrating oscillatory rheology with all-atom molecular dynamics simulations. Frequency sweeps across 5-15 mg mL-1, two ionic media (0.154 mol L-1 NaCl and 0.28 mol L-1 LiCl), and 10-60 C were used to map liquid-like, transitional, and elastic-dominated regimes. Increasing concentration strengthened network behavior, but the two salts followed distinct pathways: NaCl promoted a more coherent progression toward elastic dominance and more thermorheologically compatible relaxation behavior, whereas LiCl produced a high-dissipation intermediate regime and stronger temperature dependence. Simulations of a minimal multichain model comprising eight GlcNAc10 oligomers at approximately 15.8 mg mL-1 showed that NaCl favored larger, more compact assemblies despite weak and short-lived Na+-oxygen coordination. LiCl formed sharper, longer-lived first-shell contacts but maintained smaller and more expanded assemblies. Ion-mediated interchain bridges were sparse and transient. The combined results show that local cation binding strength does not directly predict collective network formation and support a dynamic physical-network mechanism governed by salt-specific coupling among hydration, ion exchange, chain packing, and reversible interchain association.

biophysics↗

Targeting Dengue Virus NS3 Helicase: Biochemical and Computational Evaluation of Catechins from Camellia sinensis as Potential Therapeutic Leads

Dengue virus serotype 2 is a human pathogenic flavivirus encoding non-structural protein 3 (DEN2-NS3), a superfamily-2 viral helicase. DEN2-NS3 contains an N-terminal protease domain and a C-terminal RNA helicase/nucleoside 5'-triphosphatase (NTPase) domain essential for replication. The enzyme utilizes energy from NTP hydrolysis to translocate 3'-to-5' along a duplex RNA substrate. Prompted by the high potency of (--)-epigallocatechin gallate (EGCG) against Zika virus, this study investigated if three catechins, EGCG, (--)-epicatechin gallate (ECG), and (--)-epigallocatechin (EGC), would be potent inhibitors of DEN2-NS3. Enzyme-inhibition assays demonstrated that the catalytic domain, DEN2-NS3(S171-K618), was strongly inhibited by the galloylated catechins (EGCG and ECG), verified by an enzyme-coupled confirmatory assay. Inhibition constants (Ki) and suggestive inhibition modes relative to NTPase activity were Ki = 400 {+/-} 86.6 nM for EGCG (mixed-mode), Ki = 550 {+/-} 250 nM for ECG (uncompetitive), and Ki = 18.3 {+/-} 4.2 {micro}M for EGC (mixed-mode). The coronavirus inhibitor SSYA10-001 inhibited DEN2-NS3 (Ki = 10.2 {+/-} 0.3 {micro}M, mixed-mode). Computational workflows using SiteMap identified a predicted druggable pocket associated with the RNA-binding region, involving residues ASP290, ARG387, ASP409, MET429, HIS487, ASP541, ARG599, and ASP603. Catechins were analyzed through 200-ns molecular dynamics simulations to evaluate binding stability. Computational results revealed that EGCG and ECG maintained high stability, forming highly persistent shared amino acid contacts (>45% occupancy) with ASP603, ARG599, ASP541, and ARG387. Biochemical and computational data support these galloylated catechin leads, suggesting a plausible binding model within an amphipathic pocket. Future structural optimization into stable prodrug derivatives could yield promising antiviral candidates.

biochemistry↗

Integrative Computational Analysis of VCX2 in Hepatocellular Carcinoma: From Potential Biomarker Discovery to Therapeutic Targeting with Peruvian Natural Products

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, often developing in the context of chronic liver disease, fibrosis, and cirrhosis. Identifying novel biomarkers with diagnostic and therapeutic potential is essential, particularly those relevant across multiple cancer types. This study integrates single-cell RNA sequencing (scRNA-seq) data from healthy and diseased liver tissues, analyzing different cellular lineages to identify genes involved in fibrosis, angiogenesis, immune modulation, and apoptosis regulation. Uniform Manifold Approximation and Projection (UMAP) clustering, differential gene expression (DEG) analysis, and protein-protein interaction (PPI) network construction were employed to identify genes contributing to tumor progression and metabolic reprogramming. Key genes, including Transmembrane BAX Inhibitor Motif Containing 4 (TMBIM4), Regulator of G-protein signaling 5 (RGS5), CEA Cell Adhesion Molecule 7 (CEACAM7), and Variable Charge X-Linked 2 (VCX2), exhibited significant roles in tumorigenesis and chromosomal stability. VCX2, a cancer/testis antigen, emerged as a potential biomarker and druggable target due to its altered expression among multiple cancers. Structural modeling and molecular docking (MD) of VCX2 identified a high affinity binding pocket, guiding a virtual screening of Peruvian natural products. Luteolin-5-O-glucoside, from Equisetum arvense, was identified as the most promising compound, showing a strong docking score (-7.42 kcal/mol) and favorable binding free energy ({Delta}G_bind = -40.13 kcal/mol). MMGBSA calculations revealed stabilizing hydrogen bonds with PRO91, GLU97, and GLU109, reinforcing its strong binding stability. These findings position VCX2 as a promising target for HCC therapy and suggest Luteolin-5-O-glucoside as a lead compound with high drug-like potential. Further studies should focus on experimental validation, molecular dynamics simulations, and structure-activity relationship (SAR) optimization to advance VCX2-targeted therapies. Highlight statementsO_LIVCX2 as a Biomarker exhibited differential expressions in HCC versus healthy liver tissue and a suggested role in tumor progression and chromosomal stability. C_LIO_LILuteolin-5-O-glucoside from Equisetum arvense was identified as a promising compound: strong docking score (-7.42 kcal/mol), favorable binding free energy ({Delta}G_bind = -40.13 kcal/mol), and stabilized interactions with key amino acids (PRO91, GLU97, GLU109). C_LIO_LIVCX2 may serve as an oncogenic driver; small molecule inhibition could desensitize tumor cells that need further refinement and validation of structural models due to lack of experimentally resolved crystal structure. C_LIO_LIVCX2 is a novel biomarker and drug target for HCC with Luteolin-5-O-glucoside presents potential for targeted therapy, paving the way for precision medicine approaches. C_LI

bioinformatics↗

Exploring the Potential of Malvidin and Echiodinin as Probable Antileishmanial Agents Through In Silico Analysis And In Vitro Efficacy

Leishmaniasis is a neglected tropical disease, caused by distinct Leishmania species, which have significant public health challenges due to treatment limitations such as toxicity, high cost, and drug resistance. This study explores the in vitro potential of Malvidin and Echioidinin as probable antileishmanial agents against Leishmania amazonensis, L. braziliensis, and L. infantum, comparing their efficacy to Amphotericin B (AmpB), a standard drug. Malvidin was more potent than Echioidinin across all parasite stages and species. For L. amazonensis, Malvidins inhibitory concentration (IC50) values were 197.71{+/-}17.20 {micro}M and 258.07{+/-}17 {micro}M (stationary and axenic amastigotes, respectively); whereas Echioidinin revealed IC50 values of 272.99{+/-}29.90 M and 335.96{+/-}19.35 M (stationary and axenic amastigotes, respectively). AmpB showed IC50 values of 0.06{+/-}0.01 {micro}M and 0.10{+/-}0.03 {micro}M, respectively. Malvidin demonstrated lower cytotoxicity activity in mammalian cells with a cytotoxic concentration (CC50) value of 2,920.31{+/-}80.29 {micro}M, while AmpBs showed a value of 1.06{+/-}0.12 {micro}M. Malvidin also exhibited favorable selectivity index (SI) values. Malvidin reduced infection rates by up to 35.75% in L. amazonensis-infected macrophages. In silico analysis uncovered strong binding interactions between Malvidin and enzyme arginase in the three species, with key residues such as HIS139 and PRO258 playing a crucial role. Tissue-specific markers expression analysis highlighted the potential Malvidins modulation of genes involved in oxidative stress and DNA repair, including glyoxalase 1 (GLO1) and apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1). The in vitro and in silico data corroborate the hypothesis that Malvidin is safe and can control the Leishmania parasites as a new natural compound for treatment. To further assess its therapeutic potential, in vivo studies are required to evaluate Malvidins efficacy, safety, and pharmacokinetics in animal models, which will be essential for validating its role as a candidate for leishmaniasis treatment.

bioinformatics↗