María José Sevilla-Sánchez

Glioblastoma is the most common and aggressive malignant brain tumor, characterized by poor response to current therapies and inevitable recurrence. Novel therapeutic strategies are urgently needed. Lansbermin‐I , a disintegrin isolated from the venom of Porthidium lansbergii lansbergii , was purified, sequenced, structurally modeled, and evaluated for its antitumor potential against the human Glioblastoma cell line T98G. Cytotoxicity assays revealed a dose‐dependent effect, with Lansbermin‐I inducing up to 38.1% cell death at 100 μg/mL, surpassing the activity of temozolomide (34.9%) while exhibiting lower toxicity on non‐tumorigenic human astrocytes (28% vs. 37%). Lansbermin‐I also inhibited T98G adhesion to fibronectin by nearly 80% ( p < 0.0001), suggesting interference with integrin‐mediated interactions. Flow cytometry demonstrated a significant increase in apoptotic cells (60% vs. 36% in control) and cell cycle arrest at the G1 phase. In silico docking studies supported a strong interaction of Lansbermin‐I with integrin αvβ3, comparable to that of fibronectin, reinforcing its potential mechanism of action through the disruption of adhesion and survival signaling. Collectively, these findings highlight Lansbermin‐I as a promising selective prototype for Glioblastoma therapy. Further studies are warranted to elucidate its molecular targets and evaluate its efficacy in preclinical models.

Background: owing to the difficulties for accessing health centers and the limited availability of antivenoms in rural areas of Colombia, in many rural communities people rely on traditional medicine based on the use of plant extracts as a therapeutic resource for the snakebite envenoming. In the department of Nariño, the potential of these alexiteric plants is unknown. This work determined the cultural importance of Neurolaena lobata (L.) Cass., one of the plants most frequently used by the rural communities of Tumaco, municipality with high incidence of poisonings, and assessed the efficacy of an extract of this plant to inhibit toxic effects of the venom of the snake Bothrops asper. Methods: semi-structured interviews were conducted with 14 randomly sampled individuals and the Cultural Importance index (CI) of the plant was calculated. Phytochemical tests were carried out and a battery of biological assays was applied to determine the neutralizing capacity of the extract on the lethal, coagulant, hemorrhagic, and myotoxic activities of the venom. Results: the CI of this plant (0.0544) reflects its ethnobotanical value for the rural communities of Tumaco. The ethanolic extract from the leaves contains tannins, flavonoids, alkaloids, saponins, and sesquiterpene lactones. Neutralization assays revealed that the extract inhibited the coagulant activity of B. asper venom, but failed to inhibit the myotoxic, and lethal activities, and only partially reduced the hemorrhagic effect. Moreover, the extract showed toxicity when assessed for lethality and myotoxicity. Conclusions: despite the cultural importance of the plant, our experimental findings do not support the claim that the crude extract of N. lobata inhibits the toxicity of the venom of B. asper of Colombia. Keywords: Bothrops asper, Neurolaena lobata, alexiteric plants.

The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A₂ can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A₂ “Pllans-II,” isolated from Porthidium lansbergii lansbergii snake venom, displayed antitumoral activity on cervical cancer and did not alter the viability of non-tumorigenic cells. However, until now, there was no evidence of its safety at the local and systemic levels, nor had experiments been developed to demonstrate that its production using recombinant technology allows us to obtain a molecule with effects similar to those generated by native phospholipase. Thus, we evaluated the impact caused by Pllans-II on murine biomodels, determining whether it induced local hemorrhage or increased pro-inflammatory and liver damage markers and histological alterations in the liver and kidneys. Additionally, the protein was produced using recombinant technology using a pET28a expression vector and the BL21 (DE3) Escherichia coli strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that Pllans-II did not generate hemorrhagic activity, nor did it increase the pro-inflammatory cytokines IL-6, IL-1B, or TNF-α at doses of 3.28, 1.64, and 0.82 mg/kg. There was also no evidence of organ damage, and only ALT and AST increased in mild levels at the two highest concentrations. Additionally, the recombinant version of Pllans-II showed conservation in its catalytic activity and the ability to generate death in HeLa and Ca Ski cells (42% and 23%, respectively). These results demonstrate the innocuity of Pllans-II at the lowest dose and constitute an advance in considering a molecule produced using recombinant technology a drug candidate for selective attacks against cervical cancer.

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient’s quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans−II, a phospholipase A₂ type-Asp49 from Porthidium lansbergii lansbergii snake venom, has shown selective attack against the HeLa and Ca Ski cervical cancer cell lines. This work suggests that the cytotoxic effect generated by Pllans−II on HeLa cells is triggered without affecting the integrity of the cytoplasmic membrane or depolarizing the mitochondrial membranes. The results allow us to establish that cell death in HeLa is related to the junction blockage between α₅β₁ integrins and fibronectin of the extracellular matrix. Pllans−II reduces the cells’ ability of adhesion and affects survival and proliferation pathways mediated by intracellular communication with the external environment. Our findings confirmed Pllans−II as a potential prototype for developing a selective chemotherapeutic drug against cervical cancer.

Two snakebites by Micrurus ortoni in Colombia and one by M. hemprichii in Peru were reported. In two cases mild to moderate motor neurological affections was observed and, in all cases, there was a marked sensory effect with hyperesthesia and hyperalgesia radiating from the bite site to the entire ipsilateral half-body. As an additional finding, the sole patient who received antivenom (which did not correspond with the type of poison), developed equine serum sickness eight days after its application. The results of laboratory tests are presented and discussed, including an electromyographic study, the photographic record of the clinical manifestations and the causative agents.

Introducción. El ofidismo en Colombia es un problema de salud pública, lo cual se hace evidente al examinar los datos epidemiológicos a nivel latinoamericano, pues el país ocupa el tercer lugar en número de accidentes ofídicos después de Brasil y México.Objetivo. Hacer un análisis retrospectivo de los casos de accidente ofídico ocurridos entre 2009 y 2018 en el departamento de Cauca, según los datos del Sistema de Vigilancia en Salud Pública (Sivigila) registrados en el Instituto Departamental de Salud del Cauca.Materiales y métodos. Se recopiló e interpretó la información consignada en las fichas de notificación obligatoria de accidente ofídico en los 10 años de estudio. Se determinaron la incidencia y la frecuencia de accidentes según la distribución geográfica y los agentes causales, y se analizaron las variables socioeconómicas relacionadas.Resultados. Se registraron 1.653 casos y una baja mortalidad. Los géneros Bothrops y Bothriechis causaron la mayoría (77,43 %) de los accidentes, seguidos por el género Micrurus (2,9 %). La mayoría de las notificaciones procedían del sur del departamento; las personas de sexo masculino y los agricultores fueron los más afectados, con mordeduras en las extremidades superiores principalmente. Las principales manifestaciones del envenenamiento fueron las hemorrágicas, más frecuentes que la necrosis y la infección. Aunque el criterio para utilizar la seroterapia no siempre fue el mejor, las complicaciones iatrogénicas no fueron frecuentes.Conclusiones. Los municipios de El Tambo y Piamonte, las personas de sexo masculino y las áreas rurales, fueron las variables más afectadas por el ofidismo, principalmente el ofidismo botrópico. Las mayores incidencias se presentaron en la zona sur del Cauca, en las cuencas de los ríos Patía y Caquetá.

Introducción. El ofidismo es un relevante problema de salud pública y, en Colombia, se incluyó como un evento de notificación obligatoria desde el año 2004. Por ser un país tropical con gran diversidad ecosistémica, ocupa el tercer puesto en Latinoamérica, después de México y Brasil, en presentar el mayor número de accidentes ofídicos.Objetivo. Realizar un análisis retrospectivo del accidente ofídico en el departamento de Nariño, con base en los eventos notificados entre los años 2008 y 2017 al Instituto Departamental de Salud de Nariño y al Sistema de Vigilancia en Salud Pública de Colombia.Materiales y métodos. Se hizo un análisis de tipo descriptivo y retrospectivo a partir de la recopilación e interpretación de la información consignada en las fichas de notificación para accidente ofídico del Instituto Departamental de Salud de Nariño, entre los años 2008 y 2017. Se representó la frecuencia del accidente ofídico a nivel municipal mediante la elaboración de un mapa y se identificaron los géneros responsables del mismo. Resultados. Se reporta un total de 1.110 casos. El 78,13 % de los municipios hizo alguna notificación. Se observa un patrón de aumento constante en el número de casos durante los 10 años, a excepción de 2017. Las características sociodemográficas se mantuvieron durante el periodo de estudio.Conclusiones. El municipio de San Andrés de Tumaco, el sexo masculino y las áreas rurales son los principales afectados por el ofidismo causado, en mayor medida, por el género Bothrops. La mayor incidencia se presentó en el mes de julio.