Evaluation of the Insecticidal Potential of Heterotheca inuloides Acetonic and Methanolic Extracts against Spodoptera frugiperda and Their Ecotoxicological Effect on Poecilia reticulata.

For the management of Spodoptera frugiperda, botanical extracts have been used to reduce the environmental impacts of synthetic chemical pesticides. In the present investigation, the insecticidal activity of the acetonic and methanolic extracts of Heterotheca inuloides (Asteraceae) and of the main compound 7-hydroxy-3,4-dihydrocadalene on this pest as well as its ecotoxicological effect on Poecilia reticulata were evaluated. A greater insecticidal response was obtained from the acetonic extracts than from the methanolic extracts, with LC50 values of 730.4 ppm and 711.7 ppm for samples 1 and 2, respectively. Similarly, there was a lethal effect on 50% of the P. reticulata population at low concentrations in the acetonic extract compared to the methanolic extract. The sesquiterpene 7-hydroxy-3,4-dihydrocadalene has greater insecticidal activity by presenting an LC50 of 44.36 ppm; however, it is classified as moderately toxic for guppy fish.

Timectomía toracoscópica en pacientes con Miastenia Gravis juvenil

Objetivo: Describir la evolución clínica postquirúrgica de una serie de casos de pacientes con Miastenia Gravis juvenil (MGJ) tratados con timectomía por toraoscópica videoasistida (TVA) derecha. Materiales y Métodos: Estudio retrospectivo que incluyó 13 pacientes pediátricos con diagnóstico de MGJ sometidos a timectomía toracoscópica derecha en la Unidad Médica de Alta Especialidad Hospital de Pediatría, Centro Médico Nacional Siglo XXI de México, entre marzo de 2016 y abril de 2022. Los pacientes fueron caracterizados clínicamente y la enfermedad fue clasificada de acuerdo a los criterios de Osserman. La evolución postquirúrgica se evaluó con la clasificación de DeFilippi para determinar la proporción de pacientes con mejoría y la remisión completa. Resultados: Los pacientes incluidos fueron, en su mayoría, mujeres (84,6%) con edad promedio al diagnóstico fue de 11,1 ± 3,1 años. Las cuatro clasificaciones de MG fueron incluidas, con mayor proporción de MG generalizada leve (38,5%), seguida de ocular (23,1%) y generalizada moderada grave (23,1%). La evaluación de la progresión postquirúrgica demostró que a los tres meses de seguimiento 92,3% presentó mejorías, incluyendo la disminución del uso de medicamentos. La remisión total solo se registró en uno de los pacientes. Los pacientes que tuvieron cirugía antes de los 12 meses de evolución de la MGJ presentaron mejores resultados post timectomía por TVA. Conclusión: Se demostró la utilidad de timectomía por TVA en pacientes pediátricos mexicanos con MGJ. Nuestra experiencia agrega evidencia de que los pacientes pediátricos se benefician de la timectomía, mejorando su estado clínico y disminuyendo el uso de medicamentos y complicaciones e la enfermedad.

Objective: To describe the post-surgical clinical evolution of a case series of patients with juvenile myasthenia gravis (JMG) treated with right video-assisted thoracoscopic (TVA) thymectomy. Materials and Methods: Retrospective study that included 13 pediatric patients with JMG who underwent right TVA thymectomy at the Siglo XXI National Medical Center of Mexico between March 2016 and April 2022. Patients were clinically characterized, and the disease was classified according to Osserman's criteria. Post-surgical evolution was evaluated using the DeFilippi classification to determine the proportion of patients with improvement and complete remission. Results: The included patients were mostly women (84.6%) with a mean age at diagnosis of 11.1 ± 3.1 years. The four MG classifications were included, with the highest proportion of mild generalized MG (38.5%), followed by ocular (23.1%) and moderate-severe generalized (23.1%). The evaluation of post-surgical progression showed that after three months of follow-up, 92.3% presented improvements, including a decrease in the use of medications. Complete remission was only recorded in one of the patients. Patients who underwent surgery before 12 months of evolution of JMG had better results after TVA thymectomy. Conclusion: The usefulness of TVA thymectomy in Mexican pediatric patients with JMG was demonstrated. Our experience adds evidence that pediatric patients benefit from thymectomy by improving their clinical status and decreasing the use of medications and complications of the disease.

The cytotoxicity effect of 7-hydroxy-3,4-dihydrocadalene from Heterotheca inuloides and semisynthetic cadalenes derivates towards breast cancer cells: involvement of oxidative stress-mediated apoptosis.

Background: Heterotheca inuloides, traditionally employed in Mexico, has demonstrated anticancer activities. Although it has been proven that the cytotoxic effect is attributed to cadinane-type sesquiterpenes such as 7-hydroxy-3,4-dihydrocadalene, the mechanism of action by which these agents act in tumor lines and their regulation remain unknown. This study was undertaken to investigate for first time the cytotoxic activity and mechanism of action of 7-hydroxy-3,4-dihydrocadalene and two semi-synthetic cadinanes derivatives towards breast cancer cells. Methods: Cell viability and proliferation were assayed by thiazolyl blue tetrazolium bromide (MTT) assay and Trypan blue dye exclusion assay. Cell migration measure was tested by wound-healing assay. Moreover, the reactive oxygen species (ROS) and lipid peroxidation generation were measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay and thiobarbituric acid reactive substance (TBARS) assay, respectively. Furthermore, expression of caspase-3, Bcl-2 and GAPDH were analyzed by western blot. Results: The results showed that 7-hydroxy-3,4-dihydrocadalene inhibited MCF7 cell viability in a concentration and time dependent manner. The cytotoxic potency of semisynthetic derivatives 7-(phenylcarbamate)-3,4-dihydrocadalene and 7-(phenylcarbamate)-cadalene was remarkably lower. Moreover, in silico studies showed that 7-hydroxy-3,4-dihydrocadalene, and not so the semi-synthetic derivatives, has optimal physical-chemical properties to lead a promising cytotoxic agent. Further examination on the action mechanism of 7-hydroxy-3,4-dihydrocadalene suggested that this natural product exerted cytotoxicity via oxidative stress as evidenced in a significantly increase of intracellular ROS levels and in an induction of lipid peroxidation. Furthermore, the compound increased caspase-3 and caspase-9 activities and slightly inhibited Bcl-2 levels. Interestingly, it also reduced mitochondrial ATP synthesis and induced mitochondrial uncoupling. Conclusion: Taken together, 7-hydroxy-3,4-dihydrocadalene is a promising cytotoxic compound against breast cancer via oxidative stress-induction.

Unreported ent-rosane diterpenes from Croton niveus Jacq. (Euphorbiaceae). Cytotoxic activity and docking studies.

From the bioactive extract of the euphorbiaceous Croton niveus Jacq., three previously unreported ent-rosane diterpenes have been isolated and characterized by conventional methods, in addition to the known compounds lupeol, cajucarinolide and some phytosterols. Two of the ent-rosane diterpenes displayed activity against HCT-15 and PC-3 cancer cell lines, and the results of docking calculations of these compounds with NF-κB and STAT3 receptors agreed with the proposed mode of action of diterpenes against PC-3 cells.

Lichen community structure and richness in three mid-elevation secondary forests in Costa Rica / Estructura y riqueza de la comunidad liquénica de tres bosques secundarios de elevación media en Costa Rica

Abstract Introduction: Lichen diversity, community structure, composition and species abundance have been used as indicators of the integrity and ecological continuity of tropical forest ecosystems. Objectives: To assess corticolous lichen species composition, diversity, and ecological importance of three forested stands differing in time of abandonment as indicators of how passive restoration influences the lichen community assemblage. Methods: We surveyed individual lichens on tree stems of a reference old secondary forest and a young secondary forest (50 and 14-year-old natural regeneration after pasture abandonment, respectively), and in a 35-year-old exotic cypress tree plantation, in the oriental Central Valley, in Orosí, Costa Rica. Standard diversity, similarity indexes, and the importance value index were calculated. An NMDS analysis was performed on the community structure parameters and in a presence-absence matrix. Results: We found 64 lichen species in 25 families with 42, 21, and 23 species, and 20, 10, and 15 families, in the young and old secondary forests, and the cypress plantation, respectively. Cryptothecia sp. possessed the highest importance across sites. More than 87 % of the species are rare. The combined IVI of the top three families were: 36, 48.5, and 74.8 % in the young and old forests and the Cypress plantation sites, respectively. Overall, Arthoniaceae is in the top three families. The young forest had the highest species richness, but the old forest presented the best evenness. Similarity and diversity indexes suggest a particularly low resemblance in the lichen communities but a smooth gradient differentiation between the three forests, which was confirmed by the NMDS test. The homogeneity test identified great differences in ecological importance and composition. Conclusions: This region contains a distinctive assemblage of species resulting in a strong community differentiation by site, reflecting the influence of ecophysiological and microclimatic factors that define lichen establishment and survival and suggesting a great regional beta diversity, within a fragmented landscape. Greater connectivity and passive restoration strategies resulted in greater diversity and a more heterogeneous community structure on both forests than the corticolous community of the abandoned plantation. Protection of forest fragments will maximize the integrity of future forests.

Resumen Introducción: La diversidad de líquenes, la estructura y composición de la comunidad y la abundancia de algunas especies y familias se ha usado como indicadores de la salud y continuidad ecológica de los ecosistemas boscosos tropicales. Objetivos: Evaluar la composición, diversidad e importancia ecológica de las especies de líquenes en tres ecosistemas boscosos que difieren en el tiempo regeneración natural, como indicadores de la influencia de la restauración pasiva en el ensamble de la comunidad de líquenes cortícolas. Métodos: Se midieron los líquenes individuales sobre los troncos de árboles en un bosque secundario avanzado (OF), en un bosque secundario joven (YF, con 50 y 14 años de regeneración natural tras abandono del potrero, respectivamente), y en una plantación abandonada de ciprés exótico con 35 años de edad (CP), en la región oriental del Valle Central de Costa Rica. Se calcularon los índices estándares de diversidad, similitud y valor de importancia (IVI), además de un análisis de NMDS sobre los parámetros de la estructura de la comunidad en una matriz de presencia-ausencia. Resultados: Encontramos 64 especies en 25 familias, con 42, 23 y 21 especies y 20, 10 y 15 familias en los sitios YF, CP y OF, respectivamente. Una especie de Cryptothecia sp. presentó el IVI más alto en los tres bosques. Más del 87 % de las especies son raras. El IVI combinado de las tres familias más importantes fue: 36, 48.5 y 74.8 % en los sitios: YF, OF y CP, respectivamente. Arthoniaceae está entre las tres familias más importantes en los tres sitios. El YF es el sitio con más especies, pero el sitio OF presentó la mayor igualdad. Los índices de similitud y diversidad sugieren una semejanza particularmente baja entre las comunidades liquénicas, pero separadas por una gradiente de diferenciación difusa entre los tres sitios, lo cual es confirmado por el análisis NMDS. La prueba de homogeneidad confirmó grandes diferencias en la importancia ecológica y la composición. Conclusiones: La región contiene un ensamblaje propio de especies que resulta en una fuerte diferenciación comunitaria entre bosques, reflejo de la influencia de factores ecofisiológicos y microclimáticos en el establecimiento y supervivencia de líquenes; lo que sugiere una gran diversidad beta regional, en un paisaje fragmentado. Una mayor conectividad y estrategias de restauración pasiva dieron como resultado una mayor diversidad y una estructura comunitaria más heterogénea en ambos bosques que la comunidad cortícola de la plantación exótica abandonada. La protección de fragmentos forestales maximizará la integridad de los bosques futuros.

Altered Light Sensitivity of Circadian Clock in Shank3+/- Mouse.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan-McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3+/- mouse, to study the circadian rhythm architecture of locomotion behavior and its entrainment to light. We also analyzed the synapse between the retinohypothalamic tract (RHT) and the suprachiasmatic nucleus (SCN), employing tract tracing and immunohistochemical techniques. We found that Shank3+/- mice were not impaired in the SCN circadian clock, as indicated by a lack of differences between groups in the circadian architecture in entrained animals to either long or short photoperiods. Circadian rhythm periodicity (tau) was unaltered between genotypes in constant darkness (DD, dim red light). Similar results were obtained in the re-entrainment to shifts in the light-dark cycle and in the entrainment to a skeleton photoperiod from DD. However, Shank3+/- mice showed larger phase responses to light pulses, both delays and advances, and rhythm disorganization induced by constant bright light. Immunohistochemical analyses indicated no differences in the RHT projection to the SCN or the number of SCN neurons expressing the N-methyl-D-aspartate (NMDA) receptor subunit NR2A, whereas the Shank3+/- animals showed decreased c-Fos induction by brief light pulses at CT14, but increased number of vasoactive intestinal polypeptide (VIP)-positive neurons. These results indicate alterations in light sensitivity in Shank3+/- mice. Further studies are necessary to understand the mechanisms involved in such increased light sensitivity, probably involving VIP neurons.

Priming of seeds with INA and its transgenerational effect in common bean (Phaseolus vulgaris L.) plants.

Priming is a mechanism of defense that prepares the plant's immune system for a faster and/or stronger activation of cellular defenses against future exposure to different types of stress. This enhanced resistance can be achieved by using inorganic and organic compounds which imitate the biological induction of systemic acquired resistance. INA (2,6 dichloro-isonicotinic acid) was the first synthetic compound created as a resistance inducer for plant-pathogen interactions. However, the use of INA to activate primed resistance in common bean, at the seed stage and during germination, remains experimentally unexplored. Here, we test the hypothesis that INA-seed treatment would induce resistance in common bean plants to Pseudomonas syringae pv. phaseolicola, and that the increased resistance is not accompanied by a tradeoff between plant defense and growth. Additionally, it was hypothesized that treating seeds with INA has a transgenerational priming effect. We provide evidence that seed treatment activates a primed state for disease resistance, in which low nucleosome enrichment and reduced histone activation marks during the priming phase, are associated with a defense-resistant phenotype, characterized by symptom appearance, pathogen accumulation, yield, and changes in gene expression. In addition, the priming status for induced resistance can be inherited to its offspring.

Antagonistic Activity of Bacteria Isolated from Apple in Different Fruit Development Stages against Blue Mold Caused by Penicillium expansum.

Blue mold caused by Penicillium expansum is one of the most significant postharvest diseases of apples. Some microorganisms associated with the surface of ripening apples possess the ability to inhibit the growth of P. expansum. However, the existing literature about their colonization in the stages before ripening is not explored in depth. This study aims to characterize the antagonistic capacity of bacterial populations from five fruit development stages of 'Royal Gala' apples. The results have shown that the density of the bacterial populations decreases throughout the ripening stages of fruit (from 1.0 × 105 to 1.1 × 101 cfu/cm2). A total of 25 bacterial morphotypes (corresponding to five genera identified by 16S RNA) were differentiated in which Bacillus stood out as a predominant genus. In the in vitro antagonism tests, 10 Bacillus strains (40%) inhibited the mycelial growth of P. expansum from 30.1% to 60.1%, while in fruit bioassays, the same strains reduced the fruit rot ranging from 12% to 66%. Moreover, the bacterial strains with antagonistic activity increased in the ripening fruit stage. B. subtilis subsp. spiziennii M24 obtained the highest antagonistic activity (66.9% of rot reduction). The matrix-assisted laser desorption ionization- time of flight mass spectrometry analysis revealed that bacteria with antagonistic activity produce antifungal lipopeptides from iturin and fengycin families.

Chemo-sensitizing activity of natural cadinanes from Heterotheca inuloides in human uterine sarcoma cells and their in silico interaction with ABC transporters.

Sensitizing activities exerted by 3,4-dihydro-7-hydroxycadalene (1), rac-3,7-dihydroxy-3(4H)-isocadalen-4-one (4) and (1R,4R)-4H-1,2,3,4-tetrahydro-1-hydroxycadalen-15-oic acid (9), the major cadinanes isolated from Heterotheca inuloides, towards multidrug-resistant MES-SA/MX2 and parental MES-SA epithelial human uterine sarcoma cell lines were evaluated. We also evaluated the in silico interactions (expressed as ΔGbinding in kcal/mol) of cadinanes 1, 4 and 9 in an in vitro assay, and also tested several structurally related natural compounds with the multidrug resistance protein (MDR1, P-glycoprotein), human multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP) structures as pharmacological targets using AutoDock and AutoDock Vina. Compound 1 potentiated the cytotoxicity of doxorubicin and mitoxantrone drugs in resistant MES-SA/MX2 cells, compared to cells treated with each drug alone. Compound 1 could reverse the resistance to doxorubicin 12.44 fold at a concentration of 5 µM. It also re-sensitized cells to mitoxantrone 3.94 fold. Hence, compound 1 may be considered as a potential chemosensitizing agent to overcome multidrug resistance in cancer. The docking analysis suggested that there are interactions between cadinanes from H. inuloides and MDR1, MRP1, and BCRP proteins mainly through π-π interactions and hydrogen bonds.

In vitro nematicidal activity of natural and semisynthetic cadinenes from Heterotheca inuloides against the plant-parasitic nematode Nacobbus aberrans (Tylenchida: Pratylenchidae).

BACKGROUND: Nacobbus aberrans (Tylenchida: Pratylenchidae) is one of the main plant-parasitic nematodes species that affects crops in Mexico, generating substantial economic losses. Traditionally, the control of the nematodes is carried out using chemical products; however, research efforts are presently focused on the search for new methods for the control of this pest. Natural products derived from plants are an alternative for the control of populations of plant-parasitic nematodes. The genus Heterotheca (Asteraceae) is characterized by containing sesquiterpenes with cadinane skeleton, and some species of this genus exert nematicidal activity. RESULTS: We determined the effects of selected Heterotheca inuloides plant metabolites and some semisynthetic derivatives on the hatching of eggs isolated from the gelatinous matrix and infective second-stage juveniles (J2) of the false root-knot nematode N. aberrans using an in vitro experimental model. Among the evaluated compounds, nematodes were more susceptible to hydroxylated and quinone compounds, whereas the remaining compounds showed moderate or no activity. The presence of the hydroxyl group is essential for nematicidal potential, with changes at the hydroxyl group modifying the nematicidal activity. CONCLUSION: Flowers of Heterotheca inuloides contain bioactive compounds that showed nematicidal activity against N. aberrans. Here we report the nematicidal activities of cadinenes isolated from the flowers of H. inuloides and their semisynthetic derivatives against the false root-knot nematode N. aberrans. © 2018 Society of Chemical Industry.

Treatment of hepatocarcinoma with celecoxib and pentoxifylline: a case report / Manejo del hepatocarcinoma con celecoxib y pentoxifilina: reporte de un caso

Background: Hepatocellular carcinoma (HCC) is the sixth most frequent tumor worldwide and it is responsible for approximately 750 000 deaths each year. It is the third leading cause of cancer death in Mexico. Despite the existing therapeutic regimens, HCC has a poor prognosis with a life expectancy of approximately one month in advanced cases. The use of celecoxib and pentoxifylline has recently been reported in tumor patients with promising results due to its anti-inflammatory, antiangiogenic, antifibrotic and proapoptotic effects. Nonetheless, the combination of both drugs for the treatment of HCC has never been employed. Clinical case: 58-year-old male patient, who arrived to the examination room for presenting nausea, jaundice, asthenia, adynamia and encephalopathy grade I-II. The patient had a history of alcoholism for 47 years and diagnosis of cirrhosis in Child C stage. An image with focal lesion in the right lobe of 8 x 8 cm, which was highly vascularized, suggested HCC by means of imaging studies (ultrasound, computed axial tomography [CAT] and magnetic resonance imaging). Management began in January, 2015, and continues until today with 400 mg of pentoxifylline every 12 hours, 200 mg of celecoxib every 12 hours and vitamin supplements. Conclusion: After one month, patient showed a surprising response, reduction in tumor size almost in its entirety, improvement of clinical condition, and turned into Child A stage. Eight months after treatment it was observed by CAT that the tumor had practically disappeared. Patient has survived for more than two years. These results are encouraging; however, it is necessary to conduct multicenter studies that prove the efficacy of the treatment.

Introducción: El hepatocarcinoma (HPC) es el sexto tumor más frecuente a nivel mundial y provoca aproximadamente 750 000 muertes al año. Representa la tercera causa de muerte por cáncer en México. A pesar de los esquemas terapéuticos existentes, el pronóstico en el HPC es malo, con un promedio aproximado de vida de un mes en casos avanzados. Recientemente se ha reportado el uso de celecoxib y pentoxifilina en pacientes tumorales con resultados prometedores debido a sus efectos antiinflamatorios, antiangiogénicos, antifibróticos y proapoptóticos. Sin embargo, nunca han sido usados en combinación para el tratamiento de HPC. Caso clínico: Paciente masculino de 58 años que acudió a consulta por presentar náuseas, ictericia, astenia, adinamia y encefalopatía grado I-II; tenía antecedente de alcoholismo durante 47 años y diagnóstico de cirrosis en estadio Child C. Mediante ultrasonido, tomografía axial computarizada (TAC) y resonancia magnética se evidenció una imagen con lesión focal en lóbulo derecho de 8 x 8 cm, altamente vascularizada, sugestiva de HPC. Se inició manejo en enero de 2015 y el paciente continúa hasta la fecha con pentoxifilina (400 mg/12 h), celecoxib (200 mg/12 h) y suplementos vitamínicos. Conclusión: Después de un mes el paciente mostró una respuesta sorprendente, reducción del tamaño de la lesión casi en su totalidad, mejoría del estadio clínico y cambió a un estadio Child A. Ocho meses después de implementar el tratamiento se observó por medio de TAC que el tumor casi había desaparecido. El paciente ha sobrevivido por más de dos años. Los resultados son alentadores; sin embargo, es necesario realizar estudios multicéntricos que demuestren su real eficacia.

Down-regulation of PvTRX1h increases nodule number and affects auxin, starch, and metabolic fingerprints in the common bean (Phaseolus vulgaris L.).

The legume-rhizobium symbiotic relationship has been widely studied and characterized. However, little information is available about the role of histone lysine methyltransferases in the legume-rhizobium interaction and in the formation of nitrogen-fixing nodules in the common bean. Thus, this study aimed to gain a better understanding of the epigenetic control of nodulation in the common bean. Specifically, we studied the role of PvTRX1h, a histone lysine methyltransferase coding gene, in nodule development and auxin biosynthesis. Through a reverse genetics approach, we generated common bean composite plants to knock-down PvTRX1h expression. Here we found that the down-regulation of PvTRX1h increased the number of nodules per plant, but reduced the number of colony-forming units recovered from nodules. Genes coding for enzymes involved in the synthesis of the indole-3-acetic acid were up-regulated, as was the concentration of this hormone. In addition, PvTRX1h down-regulation altered starch accumulation as determined by the number of amyloplasts per nodule. Metabolic fingerprinting by direct liquid introduction-electrospray ionization-mass spectrometry (DLI-ESI-MS) revealed that the root nodules were globally affected by PvTRX1h down-regulation. Therefore, PvTRX1h likely acts through chromatin histone modifications that alter the auxin signaling network to determine bacterial colonization, nodule number, starch accumulation, hormone levels, and cell proliferation.

Mexican Arnica (Heterotheca inuloides Cass. Asteraceae: Astereae): Ethnomedical uses, chemical constituents and biological properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Heterotheca inuloides Cass. (Asteraceae) has been traditionally used to treat a wide range of diseases in Mexico in the treatment of rheumatism, topical skin inflammation, muscular pain colic, and other painful conditions associated with inflammatory processes, additionally has been used to treat dental diseases, and gastrointestinal disorders. This species has also been used for the treatment of cancer and diabetes. This review provides up-to-date information on the botanical characterization, traditional uses, chemical constituents, as well as the biolological activities of H. inuloides. MATERIAL AND METHODS: A literature search was conducted by analyzing the published scientific material. Information related to H. inuloides was collected from various primary information sources, including books, published articles in peer-reviewed journals, monographs, theses and government survey reports. The electronic search of bibliographic information was gathered from accepted scientific databases such as Scienfinder, ISI Web of Science, Scielo, LILACS, Redalyc, Pubmed, SCOPUS and Google Scholar. RESULTS: To date, more than 140 compounds have been identified from H. inuloides, including cadinane sesquiterpenes, flavonoids, phytosterols, triterpenes, benzoic acid derivatives, and other types of compounds. Many biological properties associated with H. inuloides. Many studies have shown that the extracts and some compounds isolated from this plant exhibit a broad spectrum of biological activities such as antioxidant, antitumor, anti-inflammatory, cytotoxic, and chelating activities, as well as insecticidal and phytotoxic activity. To date, reports on the toxicity of H. inuloides are limited. CONCLUSIONS: A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that ethnomedical uses of H. inuloides have been recorded in Mexico to treat rheumatism, pain, and conditions associated with inflammatory processes. Pharmacological studies have demonstrated the activity of certain compounds associated with the traditional use of the plant such as the anti-inflammatory and cytotoxic activities of the species. The available literature showed that cadinene sesquiterpenes are the major bioactive components of H. inuloides with potential pharmacological activities. Further investigations are needed to fully understand the mode of action of the major active constituents.

Ryanodine-sensitive intracellular Ca2+ channels are involved in the output from the SCN circadian clock.

The suprachiasmatic nuclei (SCN) contain the major circadian clock responsible for generation of circadian rhythms in mammals. The time measured by the molecular circadian clock must eventually be translated into a neuronal firing rate pattern to transmit a meaningful signal to other tissues and organs in the animal. Previous observations suggest that circadian modulation of ryanodine receptors (RyR) is a key element of the output pathway from the molecular circadian clock. To directly test this hypothesis, we studied the effects of RyR activation and inhibition on real time expression of PERIOD2::LUCIFERASE, intracellular calcium levels and spontaneous firing frequency in mouse SCN neurons. Furthermore, we determined whether the RyR-2 mRNA is expressed with a daily variation in SCN neurons. We provide evidence that pharmacological manipulation of RyR in mice SCN neurons alters the free [Ca2+ ]i in the cytoplasm and the spontaneous firing without affecting the molecular clock mechanism. Our data also show a daily variation in RyR-2 mRNA from single mouse SCN neurons with highest levels during the day. Together, these results confirm the hypothesis that RyR-2 is a key element of the circadian clock output from SCN neurons.

Use of BABA and INA As Activators of a Primed State in the Common Bean (Phaseolus vulgaris L.).

To survive in adverse conditions, plants have evolved complex mechanisms that "prime" their defense system to respond and adapt to stresses. Their competence to respond to such stresses fundamentally depends on its capacity to modulate the transcriptome rapidly and specifically. Thus, chromatin dynamics is a mechanism linked to transcriptional regulation and enhanced defense in plants. For example, in Arabidopsis, priming of the SA-dependent defense pathway is linked to histone lysine methylation. Such modifications could create a memory of the primary infection that is associated with an amplified gene response upon exposure to a second stress-stimulus. In addition, the priming status of a plant for induced resistance can be inherited to its offspring. However, analyses on the molecular mechanisms of generational and transgenerational priming in the common bean (Phaseolus vulagris L.), an economically important crop, are absent. Here, we provide evidence that resistance to P. syringae pv. phaseolicola infection was induced in the common bean with the synthetic priming activators BABA and INA. Resistance was assessed by evaluating symptom appearance, pathogen accumulation, changes in gene expression of defense genes, as well as changes in the H3K4me3 and H3K36me3 marks at the promoter-exon regions of defense-associated genes. We conclude that defense priming in the common bean occurred in response to BABA and INA and that these synthetic activators primed distinct genes for enhanced disease resistance. We hope that an understanding of the molecular changes leading to defense priming and pathogen resistance will provide valuable knowledge for producing disease-resistant crop varieties by exposing parental plants to priming activators, as well as to the development of novel plant protection chemicals that stimulate the plant's inherent disease resistance mechanisms.

Toxicological evaluation of the natural products and some semisynthetic derivatives of Heterotheca inuloides Cass (Asteraceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Heterotheca ineuloides Cass (Asteraceae), popularly known as árnica mexicana, is widely used in Mexican traditional medicine to treat bruises, dermatological problems, rheumatic pains, and other disorders as cancer. The major constituents in H. inuloides are cadinane type sesquiterpenes, flavonoids and phytosterols. Compounds with a cadinane skeleton have been proved to possess cytotoxic activity against human-tumor cell lines and brine shrimp, and display toxic effects in different animal species. Although this plant has been widely used, there is little available information on the safety and toxicity especially of pure compounds. AIM OF THIS STUDY: Evaluate the potential toxicity of the natural products isolated from H. inuloides and some semisynthetic derivatives. MATERIALS AND METHODS: The toxic aspects of the following natural products isolated from dried flowers of H. inuloides: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), (1R,4R)-1-hydroxy-4H-1,2,3,4- tetrahydrocadalen-15-oic acid (4), D-chiro-inositol (5), quercetin (6), quercetin-3,7,3'-trimethyl ether (7), quercetin-3,7,3',4'-tetramethyl ether (8), eriodictyol-7,4'-dimethyl ether (9), α-spinasterol (10), caryolan-1,9ß-diol (11) and 7-(3,3-dimethylallyloxy)-coumarin (12) as well as the toxic aspects of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (13), 7-benzoxy-3,4-dihydrocadalene (14), 7-acetoxycadalene (15), 7-benzoxycadalene (16), quercetin pentaacetate (17), 7-hydroxycalamenene (18), 3,8-dimethyl-5-(1-methylethyl)-1,2-naphthoquinone (19), and 4-isopropyl-1,6-dimethylbenzo[c]oxepine-7,9-dione (20). Toxic activities of compounds were determined by sulforhodamine B (SRB) assay, Artemia salina assay, RAW264.7 macrophage cells. Additionally, the acute toxicity in mouse of compound 1, the major natural sesquiterpene isolated from the acetone extract, was evaluated. RESULTS: The best cytotoxicity activity was observed for mansonone C (19) on K562 cell line with IC50 1.45 ± 0.14 µM, for 7-hydroxycadalene (2) on HCT-15 cell line with IC50 18.89 ± 1.2 µM, and for quercetin pentaacetate (17) on MCF-7 cell line with IC50 22.57 ± 2.4 µM. Sesquiterpenes mansonone C (19) and 7-hydroxy-3,4-dihydrocadalene (1) caused the strongest deleterious effects against A. salina with IC50 39.4 ± 1.07, and 45.47 ± 1.74 µM, respectively. The number of viable RAW 264.7 cells was reduced with sesquiterpenes 1 and 2 by more than 90%. In addition, the acute study of 1 revealed no lethal effects at 300 mg/kg body weight, however, a reduction in the body weight of mice, morphological changes in the tissues of the liver and kidney and toxic signs were observed at very high doses (2000 mg/kg). CONCLUSION: The results provided evidence for the cytotoxicity of Mexican arnica (H. inuloides) metabolites and may be correlated with one of the popular uses of this plant, in traditional Mexican medicine, as anticancer remedy. Among the active compounds contained in the acetone extract, the cytotoxic activity is mainly ascribable to cadinene type sesquiterpenes. In addition, evidence of acute toxicity suggests that 7-hydroxy-3,4-dihydrocadalene (1) may lead to toxicity at very high doses.

Antioxidant capacity of "Mexican arnica" Heterotheca inuloides Cass natural products and some derivatives: their anti-inflammatory evaluation and effect on C. elegans life span.

It has been suggested that the accumulation of biomolecular damage caused by reactive oxygen species (ROS) contributes to aging. The antioxidant activity is related to the ability of certain compounds to protect against the potentially harmful effect of processes or reactions involving ROS. This ability is associated with the termination of free radical propagation in biological systems. From Heterotheca inuloides various compounds which have shown to possess antioxidant capacity and scavenging ROS. The aim of this study was to determine the antioxidant capacity of additional natural components isolated from H. inuloides and some semisynthetic derivatives, their anti-inflammatory activity and the effect on Caenorhabditis elegans nematode life span. Compounds showed ability to inhibit various biological processes such as lipid peroxidation, scavenge nonbiological important oxidants such as (1)O2, OH(∙), H2O2, and HOCl and scavenge non biological stable free radicals (DPPH). Some cadinane type compounds showed possess antioxidant, ROS scavenging capacity, anti-inflammatory activity, and effect on the C. elegans life span. Flavonoid type compounds increased the life of the nematode and quercetin was identified as the compound with the greatest activity. The modification of chemical structure led to a change in the antioxidant capacity, the anti-inflammatory activity, and the survival of the worm.

In vitro activity of 'Mexican Arnica' Heterotheca inuloides Cass natural products and some derivatives against Giardia intestinalis.

Giardiasis is a gastrointestinal disease that affects humans and other animals caused by parasitic protists of the genus Giardia. Giardia intestinalis (Syn. Giardia lamblia; Giardia duodenalis) infections can cause acute or chronic diarrhoea, dehydration, abdominal discomfort and weight loss. Metronidazole is the most widely used drug for treating giardiasis. Although effective, metronidazol has undesirable secondary effects. Plants used in traditional medicine as antidiarrhoeals or antiparasitics may represent alternative sources for new compounds to treat giardiasis. Heterotheca inuloides Cass. (Asteraceae/Compositae) plant is widely used in Mexican traditional medicine. The following secondary metabolites were isolated from H. inuloides flowers: 7-hydroxy-3,4-dihydrocadalene (1), 7-hydroxycadalene (2), 3,7-dihydroxy-3(4H)-isocadalen-4-one (3), 1R,4R-hydroxy-1,2,3,4-tetrahydrocadalen-15-oic acid (4), quercetin (5), quercetin-3,7,3'-trimethyl ether (6), quercetin-3,7,3',4'-tetramethyl ether (7) and eriodictyol-7,4'-dimethyl ether (8). The activity of these compounds against Giardia intestinalis trophozoites was assessed in vitro as was the activity of the semisynthetic compounds 7-acetoxy-3,4-dihydrocadalene (9), 7-benzoxy-3,4-dihydrocadalene (10), 7-acetoxycadalene (11), 7-benzoxycadalene (12), quercetin pentaacetate (13) and 7-hydroxycalamenene (14). Among these, 7-hydroxy-3,4-dihydrocadalene (1) and 7-hydroxycalamenene (14) were the most active, whereas the remaining compounds showed moderate or no activity. The G. intestinalis trophozoites exposed to compound 1 showed marked changes in cellular architecture along with ultrastructural disorganization. The aim of this study was to evaluate the giardicidal activity of selected H. inuloides metabolites and some semisynthetic derivatives using an in vitro experimental model of giardiasis.

[Serous cystadenoma in supernumerary ovary. Case report and literature review]. / Cistoadenoma seroso en ovario supernumerario. Reporte de un caso y revisión de la bibliografía.

BACKGROUND: The ovaries accessories, ectopic and supernumerary represent a rare gynecological disorder; incidence ranges from 129,000 to 1:700,000 cases. CLINIC CASE: Patient 55 years of age who arrived at by diffuse abdominal pain 2 weeks of evolution, nausea and vomiting, with no history of chronic degenerative diseases or surgical. Palpation abdomen soft depressible globoso palpable mass at the expense of 30x20 cm, painless to superficial and deep pressure. Bimanual: anteversoflexion uterus 9 cm, 20 cm tumor, soft, fixed, mild pain in the cervical mobilization funds free bag. Laboratory tests and tumor markers for ovarian unchanged. The abdominopelvic ultrasound ecomixta reported prodomain cystic mass of 28x13x26 cm, volume 5,470 mL, with papillary projections, septa and caps 6 mm thick. Contrasted abdominal tomography: nodular image of 20 cm, heterogeneous, predominantly cystic, with septa, uptake of contrast medium in the pelvic cavity of probable ovarian origin. laparotomy was performed and found: 8 cm uterus, normal, both atrophic ovaries; 30x20 cm tumor, smooth edges, with neovascularization and areas of calcification with serous content of 5,000 cc, attached to the handles of the jejunum and ileum; transverse colon, back and tail of the pancreas; It was dissected into the retroperitoneum and great vessels, apparent root of the prevertebral fascia. CONCLUSION: The supernumerary ovary is an extremely rare disorder, but should be considered in patients with abdominal tumors.