Pulmonary fibrosis (PF) is characterized by excessive collagen deposition and impaired lung function. Pulmonary surfactant may modulate fibroblast activity and offer therapeutic benefits. We developed a natural porcine pulmonary surfactant (NPPS) enriched with 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine (PE) and evaluated its biophysical and biological properties. Biophysical analysis showed that PE improved surfactant performance by increasing surface pressure and stability. In vitro, NPPS-PE reduced collagen expression and induced apoptosis in normal human lung fibroblasts; in addition, it decreased proliferation in fibroblasts stimulated with TGF-β. In vivo, NPPS-PE improved gas exchange and significantly reduced collagen deposition in bleomycin-treated mice. These findings suggest that NPPS-PE may be a promising therapeutic strategy for fibrosing lung diseases.

Research into muscle tissue pathologies offers great opportunities for new pharmaceutical agents. Current therapies, including corticosteroids and immunosuppressants, have limited efficacy and significant adverse effects. In this context, steroidal hydrazone compound 4d was investigated for its ability to promote muscle growth and regeneration as a potential anabolic and regenerative modulator. Flow cytometry analysis showed that 4d significantly increases cell populations in S phase, indicating a strong proliferative stimulus in pathways regulated by TNF-α, AKT, MAFbX, and SMAD2/3. Molecular docking studies showed that 4d shares strong interactions with the known MasR agonist (EP-2825), exhibiting a higher predicted binding affinity. Furthermore, 4d demonstrated the ability to interact with ACVR1/2A receptors, mimicking the binding profiles of known antagonists and potentially inhibiting myostatin/SMAD signaling. Taken together, experimental and computational evidence supports a dual-mechanistic model in which 4d promotes muscle proliferation and regeneration by (1) activating the MasR–PI3K/AKT/mTOR axis and (2) inhibiting the ACVR1/2A–SMAD pathway, counteracting the action of myostatin. These findings position compound 4d as a promising therapeutic candidate against muscle wasting disorders, including cancer-related cachexia, by inducing a robust and multifactorial anabolic response.

The phospholipid 1,2-dipalmitoyl-rac-glycero-3-phosphatidylethanolamine (PE) comprises two fatty acid chains: glycerol, phosphate, and ethanolamine. PE participates in critical cellular processes such as apoptosis and autophagy, which places it as a target for designing new therapeutic alternatives in diseases such as pulmonary fibrosis. Therefore, this study aimed obtain PE through a six-step organic synthesis pathway and determine its biological effect on apoptosis induction in normal human lung fibroblasts (NHLF). The first step of the organic synthesis route began with protected glycerol that was benzylated at sn-3; later, it was deprotected to react with palmitic acid at sn-1, sn-2. To remove the benzyl group, hydrogenation was performed with palladium on carbon (Pd/C); subsequently, the molecule was phosphorylated in sn-3 with phosphorus oxychloride and triethylamine, and the intermediate was hydrolyzed in an acid medium to obtain the final compound. After PE synthesis, apoptosis assessment was performed: apoptosis was induced using exposure to annexin V-FITC/propidium iodide-ECD (PI) and quantified using flow cytometry. The experiments were performed in three NHLF cell lines with different concentrations of PE 10, 100 and 1000µg/mL for 24 and 48hours. The PE obtained by organic synthesis presented a melting point of 190-192 °C, a purity of 95%, and a global yield of 8%. The evaluation of apoptosis with flow cytometry showed that at 24hours, exposure to PE 10, 100, and 1000µg/mL induces early apoptosis in 19.42%-25.54%, while late apoptosis was only significant P <0.05 in cells challenged with 100µg/mL PE. At 48hours, NHLF exposed to PE 10, 100, and 1000µg/mL showed decreasing early apoptosis: 28.69-32.16%, 12.59-18.84%, and 10.91-12.61%, respectively. The rest of the NHLF exposed to PE showed late apoptosis: 12.03-16-42%, 11.04-15.94%, and 49.23-51.28%. Statistical analysis showed a significance P <0.05 compared to the control. The organic synthesis route of PE allows obtaining rac-1,2-O-Dipalmitoyl-glycero-3-phosphoethanolamine (1), which showed an apoptotic effect on NHLF.

The title compound, C₂₉H₄₆O₃, is a steroid synthesized through a rearrangement of a sarsasapogenin derivative in acidic medium. The newly formed ring F is a tetrahydro-2H-pyran heterocycle substituted by two methyl groups placed in equatorial positions. This ring displays a chair conformation, while dihydrofuran ring E, to which it is bonded, has an envelope conformation. The molecules are associated by weak O—H...O hydrogen bonds to form chains running in the [101] direction in the crystal.

The aim of this study was to investigate the anabolic potential of novel heterosteroids in human skeletal muscle cells. A library of new heterosteroids was synthesized by selectively modifying the A and B rings of steroidal sapogenins (diosgenin, sarsasapogenin, and hecogenin), with six library members (S1, D3, D5, D7, D8 and D13) subsequently tested in vitro. Compound selection was based on computational modeling intracellular signaling pathways regulating muscle hypertrophy and atrophy, coupled with pharmacological potential evaluation using cheminformatics tools. The anabolic activity of these compounds was evaluated in the ATCC PCS-950-010 HSkM cell line, which represents normal human skeletal muscle cells. Among the compounds tested, D5 and D7 increased protein synthesis by approximately 22 % and 14 %, respectively. Compound D8 exhibited the most pronounced effect, increasing cell proliferation by approximately 50 %. Molecular docking and microarray analyses confirmed that D8 stimulates anabolism through AKT, ERK and MAPK activation, revealing the complex interplay between MAPK, PI3K and GPCR signaling pathways in the regulation of muscle cell proliferation. These findings suggest that compounds D8, D5, and D7 warrant further investigation in the context of muscle anabolism as potential therapeutic agents for targeting muscle atrophy.

En los últimos años, la simulación in silico se ha posicionado como una herramienta clave en el diseño y desarrollo de nuevos fármacos. Mediante modelos computacionales, inteligencia artificial y análisis predictivos, es posible anticipar la interacción entre moléculas bioactivas y sus posibles blancos terapéuticos, optimizando la selección de candidatos antes de los ensayos in vitro o in vivo. Este artículo presenta una revisión narrativa de investigaciones publicadas entre 2007 y 2025, en las que se destaca la aplicación de la simulación digital en áreas como la oncología, la nutrición, la odontología y enfermedades infecciosas. Herramientas como el docking molecular, la dinámica molecular, los modelos QSAR y las predicciones ADMET han reducido los costos experimentales, minimizado el uso de modelos animales y ayudado a priorizar los compuestos con mayor potencial terapéutico. La evidencia recopilada muestra la transformación de cómo podrían ser las futuras terapias y su tendencia hacia la innovación terapéutica y reducción de los tiempos y costos de investigación.