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The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases.

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This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

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Abstract This work aimed to show which treatments showed efficacy against coronavirus disease 2019 (COVID-19); therefore, the results of 37 clinical trials started in 2020 and completed in 2021 are reviewed and discussed here. These were selected from databases, excluding vaccines, computational studies, in silico, in vitro, and those with hyperimmune sera from recovered patients. We found 34 drugs, one vitamin, and one herbal remedy with pharmacological activity against symptomatic COVID-19. They reduced mortality, disease progression, or recovery time. For each treatment, the identifier and type of trial, the severity of the disease, the sponsor, the country where the trial was conducted, and the trial results are presented. The drugs were classified according to their mechanism of action. Several drugs that reduced mortality also reduced inflammation in the most severe cases. These include some that are not considered anti-inflammatory, such as Aviptadil, pyridostigmine bromide, anakinra, imatinib, baricitinib, and bevacizumab, as well as the combination of ivermectin, aspirin, dexamethasone, and enoxaparin. Nigella sativa seeds with honey have also been reported to have therapeutic activity. On the other hand, tofacitinib, novaferon with ritonavir, and lopinavir were also effective, as well as in combination with antiviral therapies such as danoprevir with ritonavir. The natural products colchicine and Vitamin D3 were only effective in patients with mild-to-moderate COVID-19, as was hydroxychloroquine. Drug repositioning has been the main tool in the search for effective therapies by expanding the pharmacological options available to patients.

Resumen El objetivo del presente trabajo fue conocer qué tratamientos mostraron efectividad contra COVID-19, para lo cual se revisan y discuten los resultados de 37 estudios clínicos iniciados durante 2020 y concluidos en 2021. Estos fueron seleccionados de bases de datos, excluyendo vacunas, estudios computacionales, in silico, in vitro y con sueros hiperinmunes de pacientes recuperados. Se documentaron 34 fármacos, una vitamina y un remedio herbolario, con actividad farmacológica ante COVID-19 sintomático. Estos redujeron la mortalidad, el progreso de la enfermedad, o el tiempo de recuperación. Para cada tratamiento se presenta identificador y tipo de estudio, la gravedad de la enfermedad, patrocinador, país donde se realizó, así como sus resultados. Los fármacos se clasificaron de acuerdo con su mecanismo de acción. Varios fármacos que redujeron la mortalidad también disminuyeron la inflamación en los casos más graves. Esto incluyendo algunos no considerados antiinflamatorios, como el aviptadil, el bromuro de piridostigmina, el anakinra, el imatinib, el baricitinib y el bevacizumab, así como la combinación de ivermectina, aspirina, dexametasona y enoxaparina. También se reportaron con actividad terapéutica las semillas de Nigella sativa con miel. Además, resultaron efectivos el tofacitinib, el novaferón con ritonavir y lopinavir, así como los antivirales en terapias combinadas como el danoprevir con ritonavir. Los productos naturales colchicina y vitamina D3, solo tuvieron actividad en los pacientes en estado leve a moderado de la COVID-19, así como la hidroxicloroquina. El reposicionamiento de fármacos fue la principal herramienta para buscar terapias efectivas ampliando las opciones farmacológicas accesibles a los pacientes.

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BACKGROUND: In countries where the consumption of mushrooms is common, hundreds of mushroom poisonings occur every year, which represents a public health problem. In Mexico, mushroom poisoning is classified as a non-bacterial gastrointestinal poisoning, which prevents timely care. OBJECTIVE: To create a free-access platform that synthesizes and standardizes the information on mycetism cases and offers tools for diagnosis and timely treatment. MATERIAL AND METHODS: In locations where cases of mycetism have occurred, information was obtained on the fungi involved, the poisonings that occurred, care protocols, and sample processing. RESULTS: Records were generated that synthesize and describe the types of mycetism with the highest probability of occurrence in Mexico. Therein, the biological characteristics of fungi, the symptoms they cause and their treatment are described. A protocol proposal for patient care and for the processing of biological samples is presented. Finally, a form is included to collect information on cases of poisoning. CONCLUSIONS: Systematized and analyzed information on mycetism allows to simplify its diagnosis, attention and treatment. The protocols for clinical care and sample processing are the basis for generating strategies that prevent deaths due to mycetism.

ANTECEDENTES: En países donde el consumo de hongos es frecuente ocurren cientos de casos de micetismos al año, por lo que representan un problema de salud pública. En México, los micetismos son clasificados como una intoxicación gastrointestinal de tipo no bacteriano, lo que impide su atención oportuna. OBJETIVO: Crear una plataforma de libre acceso que sintetice y estandarice la información de los casos de micetismos y ofrezca herramientas para su diagnóstico y tratamiento oportuno. MATERIAL Y MÉTODOS: En localidades donde han ocurrido casos de micetismos se obtuvo información sobre los hongos involucrados, las intoxicaciones ocurridas, protocolos de atención y procesamiento de muestras. RESULTADOS: Se generaron cédulas que sintetizan y describen las intoxicaciones por hongos con mayor probabilidad de ocurrencia en México. En ellas se describen las características biológicas de los hongos, síntomas que provocan y su tratamiento. Se presenta una propuesta de protocolo para la atención del paciente y para el procesamiento de muestras biológicas. Por último, se incluye un formulario para recopilar información sobre los casos de intoxicaciones. CONCLUSIONES: La información sistematizada y analizada sobre los micetismos permite simplificar su diagnóstico, atención y tratamiento. Los protocolos para la atención clínica y el procesamiento de muestras son la base para generar estrategias que eviten decesos por micetismo.

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Resumen Antecedentes: En países donde el consumo de hongos es frecuente ocurren cientos de casos de micetismos al año, por lo que representan un problema de salud pública. En México, los micetismos son clasificados como una intoxicación gastrointestinal de tipo no bacteriano, lo que impide su atención oportuna. Objetivo: Crear una plataforma de libre acceso que sintetice y estandarice la información de los casos de micetismos y ofrezca herramientas para su diagnóstico y tratamiento oportuno. Material y métodos: En localidades donde han ocurrido casos de micetismos se obtuvo información sobre los hongos involucrados, las intoxicaciones ocurridas, protocolos de atención y procesamiento de muestras. Resultados: Se generaron cédulas que sintetizan y describen las intoxicaciones por hongos con mayor probabilidad de ocurrencia en México. En ellas se describen las características biológicas de los hongos, síntomas que provocan y su tratamiento. Se presenta una propuesta de protocolo para la atención del paciente y para el procesamiento de muestras biológicas. Por último, se incluye un formulario para recopilar información sobre los casos de intoxicaciones. Conclusiones: La información sistematizada y analizada sobre los micetismos permite simplificar su diagnóstico, atención y tratamiento. Los protocolos para la atención clínica y el procesamiento de muestras son la base para generar estrategias que eviten decesos por micetismo.

Abstract Background: In countries where the consumption of mushrooms is common, hundreds of mushroom poisonings occur every year, which represents a public health problem. In Mexico, mushroom poisoning is classified as a non-bacterial gastrointestinal poisoning, which prevents timely care. Objective: To create a free-access platform that synthesizes and standardizes the information on mycetism cases and offers tools for diagnosis and timely treatment. Material and methods: In locations where cases of mycetism have occurred, information was obtained on the fungi involved, the poisonings that occurred, care protocols, and sample processing. Results: Infographics were generated that synthesize and describe the types of mycetism with the highest probability of occurrence in Mexico. Therein, the biological characteristics of fungi, the symptoms they cause and their treatment are described. A protocol proposal for patient care and for the processing of biological samples is presented. Finally, a form is included to collect information on cases of poisoning. Conclusions: Systematized and analyzed information on mycetism allows to simplify its diagnosis, attention and treatment. The protocols for clinical care and sample processing are the basis for generating strategies that prevent deaths due to mycetism.

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Increased antibiotic resistance presents a health problem worldwide. The World Health Organization published a list of pathogens considered a priority for designing new treatments. Klebsiella pneumoniae (Kp) is a top-priority microorganism, highlighting the strains that produce carbapenemases. Developing new efficient therapies or complementing existing treatments is a priority, and essential oils (EOs) provide an alternative. EOs could act as antibiotic adjuvants and enhance antibiotic activity. Employing standard methodologies, the antibacterial activity of the EOs and their synergic effect with antibiotics were detected. A string test was used to identify the impact of the EOs over the hypermucoviscosity phenotype presented by Kp strains, and Gas Chromatography-Mass Spectrometry analysis identified EOs and the composition of EOs. The potential of EOs for designing synergistic therapies with antibiotics to combat the infection of KPC diseases was demonstrated. In addition, the alteration of the hypermucoviscosity phenotype was shown as the principal mechanism of a synergic action between EOs and antibiotics. The differential composition of the EOs lets us identify some molecules that will be analyzed. Synergic activity of EOs and antibiotics can provide a solid platform for combating multiresistant pathogens that represent a severe health sector problem, such as Kp infections.

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ETHNOPHARMACOLOGICAL RELEVANCE: Several medicinal plants, including the endemic herb Cirsum ehrenbergii (Asteraceae), have been documented in manuscripts, medical and botanical books written in Mexico since the XVI century until the present. This unique circumstance is a real window in the time that allows to investigate historical and contemporary ethnopharmacological knowledge. AIM OF THE STUDY: To examine the persistence, disappearance, and transformation of ethnomedicinal knowledge of C. ehrenbergii along time. Also, to investigate the chemistry and pharmacology of this species in relation to its historical and present day main ethnomedical applications related to Central Nervous System and inflammation. MATERIALS AND METHODS: A thorough review was performed of written sources of medicinal plants from XVI and onwards. For the pharmacological studies, the organic extracts were tested in mice models to assess its antidepressant and anti-inflammatory properties. The active extracts were studied chemically. The isolated compounds were identified by 1H, 13C NMR, or characterized by GC-MS. RESULTS: Cirsum ehrenbergii was illustrated for the first time (1552) in the Libellus de Medicinalibus Indorum Herbis (Booklet of Medicinal Plants of the Indians) and named in the Nahuatl native language as huitzquilitl (edible thistle). It was there recommended as nigris sanguinis remedium (remedy for black blood), and for the treatment of illnesses with an inflammatory component. Nigris sanguinis was well known in the European medicine of that time and currently it has been interpreted as "depression". At the present time, peasants and native population in Mexico mainly name C. ehrenbergii in Spanish as cardo Santo (holy thistle). Its original Nahuatl name has been almost forgotten. However, these communities use this species, among other maladies, to heal "nervios" (anxiety and/or depression) and for anti-inflammatory purposes. These ailments and treatments resemble those recorded in the Libellus and in several medicinal plant books along centuries. The ethanol extract of C. ehrenbergii roots showed antidepressant-like activity in mice administered at 300 mg/kg, as indicated by the forced swim test (FST). The glycosylated flavonoid linarin was identified as antidepressant principle and was active at the doses of 30 and 60 mg/kg in the FST. Regarding to anti-inflammatory activity, the most active was the methylene chloride extract of the aerial parts, which contains taraxasterol, pseudotaraxasterol, ß-sitosterol and stigmasterol. CONCLUSIONS: Cirsium ehrenbergii extracts possess antidepressant-like (roots, EtOH) and anti-inflammatory (aerial parts, CH2Cl2) properties, containing active compounds. Our results sustain historical and present day ethnomedical applications of this species documented along five centuries.

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BACKGROUND: COVID-19, the disease caused by SARS-CoV-2 virus infection, has been a major public health problem worldwide in the last 2 years. SARS-CoV-2-dependent activation of innate immune receptors contributes to the strong local and systemic inflammatory reaction associated with rapid disease evolution. The receptor-binding domain (RBD) of Spike (S) viral protein (S-RBD) is essential for virus infection and its interacting molecules in target cells are still under identification. On the other hand, the search for accessible natural molecules with potential therapeutic use has been intense and remains an active field of investigation. METHODS: C57BL6/J (control) and Toll-like receptor (TLR) 4-deficient (Lps del) mice were nebulized with recombinant S-RBD. Tumor Necrosis Factor-alpha (TNF-α) and Interleukin (IL)-6 production in bronchoalveolar lavages (BALs) was determined by enzyme-linked immunosorbent assay (ELISA). Lung-infiltrating cells recovered in BALs were quantified by hematoxylin-eosin (H&E) stain. In selected groups of animals, the natural compound Jacareubin or dexamethasone were intraperitoneally (ip) administered 2 hours before nebulization. RESULTS: A rapid lung production of TNF-α and IL-6 and cell infiltration was induced by S-RBD nebulization in control but not in Lps del mice. Pre-treatment with Jacareubin or dexamethasone prevented S-RBD-induced TNF-α and IL-6 secretion in BALs from control animals. CONCLUSIONS: S-RBD domain promotes lung TNF-α and IL-6 production in a TLR4-dependent fashion in C57BL6/J mice. Xanthone Jacareubin possesses potential anti-COVID-19 properties that, together with the previously tested anti-inflammatory activity, safety, and tolerance, make it a valuable drug to be further investigated for the treatment of cytokine production caused by SARS-CoV-2 infection.

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The Libellus de Medicinalibus Indorum Herbis (Booklet of Indian Medicinal Plants) is the first book of medicinal plants written in the American continent. It was first published in 1939 as 'An Aztec Herbal'. One of the depicted plants is Huetzcanixochitl (laughing flower) interpreted as Zephyranthes fosteri (Amaryllidaceae). No chemical or pharmacological studies are reported for this species; so, we decide to investigate it. The GC/MS of the bulbs and aerial parts extracts indicated that they contain Amaryllidaceae alkaloids, among them: lycorine, 3-O-acetylpowelline, and norlycoramine. An unknown major alkaloid was isolated and identified by 1 H, 13 C-NMR and MS, as 3'-demethoxy-6-epimesembranol (1). The methanolic extract, the alkaloid fraction, and compound 1 inhibited acetylcholinesterase in vitro. Mesembrine alkaloids are found in Sceletium species (Aizoaceae). Several are known as serotonin recapture inhibitors and have been proposed as potential antidepressant drugs. The presence of 1 suggests that Z. fosteri was probably used in pre-Columbian times in Mexico as a 'stimulant and euphoriant', alike Sceletium tortuosum by several ethnic groups in South Africa.

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Resumen: El "Libellus de Medicinalibus Indorum Herbis" (Librito de las Hierbas Medicinales de los Indios) fue elaborado por los sabios indígenas Martín De la Cruz y Juan Badiano, 31 años después de la caída del imperio azteca. El primero es su autor, el segundo tradujo el manuscrito del Náhuatl al latín. Contiene numerosas recetas para tratar enfermedades humanas y 185 dibujos a color de las plantas utilizadas. En 1939 se publicó por primera vez como "Un Herbario Azteca". Empero, también contiene enfermedades y prácticas médicas europeas del siglo XVI. Presentamos una revisión actualizada de este hermoso códice, su historia, concepción, creadores y botánica; además, la química y farmacología de cinco plantas ahí citadas. El Libellus es una ventana en el tiempo que permite la investigación científica del antiguo conocimiento etnofarmacológico en Mesoamérica y documentar su persistencia, desaparición o transformación. Sin embargo, esto requiere superar desafíos lingüísticos, pero también derivados de su contexto histórico, antropológico, cultural, botánico y médico.

Abstract: The "Libellus de Medicinalibus Indorum Herbis" (Little Book of Indian Medicinal Plants) was composed by the indigenous sages Martín De la Cruz and Juan Badiano, 31 years after the Aztec Empire fall. The former was the author, and the latter translated the manuscript from the Nahuatl language to Latin. It contains numerous recipes for treating human diseases and 185 colored drawings of the prescribed plants. In 1939 it was first published as "An Aztec Herbarium". However, it also contains XVI century European diseases and medical practices. We present an updated review of this beautiful codex, its history, conception, creators, and botany; as well as, the chemistry and pharmacology of five plants therein cited. The Libellus is a window in the time that allows the scientific research of ancient ethnopharmacological knowledge in Mesoamerica and document its persistence, disappearance, or transformation. However, this requires overcoming linguistic defies, but also derived from its historical, anthropological, cultural, botanical, and medical context.

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