Antiproliferative activity of cardenolides on cell line A549: structure-activity relationship analysis.

Since the beginning, natural products have represented an important source of bioactive molecules for cancer treatment. Among them, cardenolides attract the attention of different research groups due to their cardiotonic and antitumor activity. The observed biological activity is closely related to their Na+/K+-ATPase inhibition potency. Currently, the discovery of new compounds against cancer is an urgent need in modern pharmaceutical research. Thus, the aim of this work is to determine the physicochemical properties and substituent effects that module the antiproliferative activity of cardenolides on the human lung cancer cell line A549. We build and curate a library with results obtained from literature; molecular descriptors were calculated in PaDEL software, and SAR/QSAR analysis was performed. The SAR results showed that cardenolides were sensitive to modifications in C and D steroidal ring and required substituent groups with the function of hydrogen bond acceptor at the C3 position. QSAR models to doubly linked-type cardenolides indicated that properties as lipoaffinity and atoms with the capacity to be hydrogen bond acceptors are involved in the increment of antiproliferative activity on A549 cell line. In contrast, the presence and position of very electro-negative atoms on the molecule decreased the antiproliferative effect on A549 cells. These results suggest that the antiproliferative capacity of cardenolides on the cell line A549 is strongly related to substituent groups on the C3 position, which must not be carbohydrate. Additionally, the steroidal rings C and D must remain without modifications.

Plant origin authentication of Sonoran Desert propolis: an antiproliferative propolis from a semi-arid region.

The main chemical composition of Sonoran propolis (SP), as well as its antiproliferative activity on cancer cells through apoptosis induction, has been reported. The chemical constitution of SP remained qualitatively similar throughout the year, whereas the antiproliferative effect on cancer cells exhibited significant differences amongst seasonal samples. The main goal of this study was to provide phytochemical and pharmacological evidence for the botanical source of SP and its antiproliferative constituents. A chemical comparative analysis of SP and plant resins of species found in the surrounding areas of the beehives was carried out by HPLC-UV-DAD, as well as by 1H NMR experiments. The antiproliferative activity on cancerous (M12.C3.F6, HeLa, A549, PC-3) and normal cell lines (L-929; ARPE-19) was assessed through MTT assays. Here, the main polyphenolic profile of SP resulted to be qualitatively similar to Populus fremontii resins (PFR). However, the antiproliferative activity of PFR on cancer cells did not consistently match that exhibited by SP throughout the year. Additionally, SP induced morphological modifications on treated cells characterised by elongation, similar to those induced by colchicine, and different to those observed with PFR treatment. These results suggest that P. fremontii is the main botanical source of SP along the year. Nevertheless, the antiproliferative constituents of SP that induce that characteristic morphological elongation on treated cells are not obtained from PFR. Moreover, the presence of kaempferol-3-methyl-ether in SP could point Ambrosia ambrosioides as a secondary plant source. In conclusion, SP is a bioactive poplar-type propolis from semi-arid zones, in which chemical compounds derived from other semi-arid plant sources than poplar contribute to its antiproliferative activity.

Effect of Extrusion Conditions and the Optimization of Phenolic Compound Content and Antioxidant Activity of Wheat Bran Using Response Surface Methodology.

The extrusion process (EP) consists of heat and mechanical treatments under different conditions of moisture, shear, and pressure and rapidly causes structural alterations and changes in the functional properties of the extruded material. The aim of this study was to evaluate the effect of extrusion conditions and optimize the wheat bran extrusion conditions to achieve the greatest content of phenolic compounds and antioxidant activity using response surface methodology. The EP factors evaluated were feed moisture (FM) (25-33.54%) and final extrusion temperature (T) (140-180 °C). The properties evaluated in the extruded material were bound total phenol content (BTPC), total phenolic compounds and antioxidant activity (AOX). Analysis of variance (ANOVA) and response surface methodology were used in the evaluation. The determination coefficients, (FM)2 and (T)2, very significantly affected the BTPC and bound 2,2-diphenyl-1-picrylhydrazyl content (BDPPHC). The optimization was performed by overlaying two contour plots to predict the best combination regions. The optimized extrusion conditions were the following: FM = 30% and T = 140 °C, which provided BTPC = 3547.01 µgGAE/g (predicted: 3589.3 µgGAE/g) and BDPPHC = 9.5 µmolTE/g (predicted: 10.4 µmolTE/g); and FM = 30% and T = 180 °C, which provided BTPC = 3342.3 µgGAE/g (predicted: 3727.7 µgGAE/g) and BDPPHC = 9.5 µmolTE/g (predicted: 9.3 µmolTE/g). The EP increased the phenolic compounds and AOX, and enhancement of these properties in wheat bran products could make them functional foods.

Antiproliferative activity of spinasterol isolated of Stegnosperma halimifolium (Benth, 1844).

Cancer is the major cause of death in the world, representing a significant public health problem. Plants have been shown as a great source of secondary metabolites with anticancer activity. The aim of this work was evaluated the antiproliferative activity of the methanolic extracts, chemical fractions and the compound spinasterol isolated of medicinal plant Stegnosperma halimifolium. The methanolic extracts of stem, leaf and stem/leaf was obtained by maceration. The methanolic extract of stem was purified by successive extractions with solvents as n-hexane, ethyl acetate and ethanol. The n-hexane fraction was separated by column chromatographic and monitored by thin layer chromatographic. The compound spinasterol was characterized by 1H NMR, 13C NMR and Mass Spectrometry. Methanolic extracts, chemical, chromatographic fractions and spinasterol was evaluated against RAW 264.7, M12.C3.F6, PC-3, LS-180, A549 and HeLa cancer cell lines by the standardized method MTT for determinate the antiproliferative activity. Methanolic extract of stem shown the better antiproliferative activity against the murine macrophage cancer cell line RAW 264.7. n-Hexane chemical fraction shown antiproliferative activity against human alveolar cancer cell line A549 and RAW 264.7. Was isolated and characterized a compound by NMR 1H and 13C, revealing the presence of sterol spinasterol. Spinasterol shown to have antiproliferative activity against cervical cancer cell line HeLa and RAW 264.7, indicating that spinasterol can be a responsible compound of antiproliferative activity found in the methanolic extract of Stegnosperma halimifolium.

Reynosin and santamarine: two sesquiterpene lactones from Ambrosia confertiflora with bactericidal activity against clinical strains of Mycobacterium tuberculosis.

CONTEXT: Tuberculosis is primarily caused by Mycobacterium tuberculosis (Mtb). Previous studies have shown that the dichloromethanic extract of Ambrosia confertiflora DC (Asteraceae) inhibited Mtb. OBJECTIVE: To isolate the compounds responsible for the mycobactericidal activity against clinical Mtb strains. MATERIALS AND METHODS: The dichloromethanic extract of aerial parts of A. confertiflora was separated using chromatography columns. Mycobactericidal activity of the isolated compounds was evaluated using the Alamar Blue bioassay (128-16 µg/mL, 7 days). Cytotoxicity was tested against normal cell line L929 using the MTT ([3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium]) assay (100-3.125 µg/mL, 48 h). Compound structures were elucidated by 1H and 13C uni- and bidimensional NMR. RESULTS: Two sesquiterpene lactones (SQLs) with mycobactericidal activity were identified: santamarine and reynosin. Reynosin was the most active compound, with a minimal bactericidal concentration (MBC) of 128 µg/mL against the H37Rv, 366-2009 and 104-2010 Mtb strains and a minimal inhibitory concentration (MIC) of 64, 64, 128, 128 and 128 µg/mL against the H37Rv, 104-2010, 63-2009, 366-2009 and 430-2010 Mtb strains, respectively. Santamarine had MBCs of 128 µg/mL against the H3Rv and 104-2010 Mtb strains and MICs of 128 µg/mL against the H37Rv, 366-2009 and 104-2010 Mtb strains. We also isolated 1,10-epoxyparthenolide but only showed mycobacteriostatic activity (MIC 128 µg/mL) against the Mtb strain. Compounds were tested against the L929 cell line and the calculated selectivity index was <1. DISCUSSION AND CONCLUSIONS: This is the first report of the mycobactericidal activity of these compounds against clinical Mtb strains. It is also the first report of the isolation of 1,10-epoxyparthenolide from A. confertiflora. The anti-mycobacterial activity of A. confertiflora was attributed to the SQLs identified.

Diterpenoids and Triterpenoids from the Resin of Bursera microphylla and Their Cytotoxic Activity.

A chemical study of the nonpolar fraction of a methanol-soluble extract of Bursera microphylla resin yielded a variety of di- and triterpenoids. In total, 15 compounds were isolated, of which three are new, namely, malabaricatrienone (1), malabaricatrienol (2), and microphyllanin (3). The antiproliferative activity of the major compounds was evaluated in different murine cancer cell lines (M12.C3.F6 and RAW264.7) and human cancer cells (A549, HeLa, and PC-3). The new compounds (1-3) did not show significant antiproliferative activity. The known compounds ariensin (4), burseran (5), and dihydroclusin diacetate (6) were effective against the RAW264.7 cell line, with IC50 values in the micromolar range.

In vitro anti-proliferative activity of Argemone gracilenta and identification of some active components.

BACKGROUND: Cancer is one of the leading causes of death worldwide. Natural products have been regarded as important sources of potential chemotherapeutic agents. In this study, we evaluated the anti-proliferative activity of Argemone gracilenta's methanol extract and its fractions. We identified those compounds of the most active fractions that displayed anti-proliferative activity. METHODS: The anti-proliferative activity on different cancerous cell lines (M12.C3F6, RAW 264.7, HeLa) was evaluated in vitro using the MTT colorimetric method. Identification of the active compounds present in the fractions with the highest activity was achieved by nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) analyses. RESULTS: Both argemonine and berberine alkaloids, isolated from the ethyl acetate fraction, displayed high anti-proliferative activity with IC50 values of 2.8, 2.5, 12.1, and 2.7, 2.4, 79.5 µg/mL on M12.C3F6, RAW 264.7, and HeLa cancerous cell lines, respectively. No activity was shown on the normal L-929 cell line. From the hexane fraction, a mixture of fatty acids and fatty acid esters of 16 or more carbon atoms with anti-proliferative activity was identified, showing a range of IC50 values of 16.8-24.9, 34.1-35.4, and 67.6-91.8 µg/mL on M12.C3F6, RAW 264.7, and HeLa cancerous cell lines, respectively. On the normal L-929 cell line, this mixture showed a range of IC50 values of 85.1 to 100 µg/mL. CONCLUSION: This is the first study that relates argemonine, berberine, and a mixture of fatty acids and fatty acid esters with the anti-proliferative activity displayed by Argemone gracilenta.

Antiproliferative and apoptotic activities of extracts of Asclepias subulata.

CONTEXT: Asclepias subulata Decne. (Apocynaceae) is a shrub used in the Mexican traditional medicine for the treatment of cancer. OBJECTIVE: The objective of this study was to evaluate the antiproliferative activity of methanol extract of aerial parts of A. subulata and its fractions against different cancer cell lines. Additionally, we analyzed the mechanism of action of the active fractions. MATERIALS AND METHODS: Methanol extract fractions were prepared by serial extraction with n-hexane, ethyl acetate, and ethanol. The antiproliferative activity of methanol extract and its fractions was evaluated, against several murine (M12.C3.F6, RAW 264.7, and L929) and human (HeLa, A549, PC-3, LS 180, and ARPE-19) cell lines by the MTT assay, using concentrations of 0.4-400 µg/mL for 48 h. Ethanol and residual fractions were separated using silica gel column. Apoptosis induction of cancer cells was evaluated by Annexin and JC-1 staining using flow cytometry. RESULTS: Methanol extract and its fractions showed antiproliferative activity against all human cancer cell lines tested. Methanol extract had the highest antiproliferative activity on A549 and HeLa cells (IC50 values < 0.4 and 8.7 µg/mL, respectively). Ethanol and residual fractions exerted significant antiproliferative effect on A549 (IC50 < 0.4 µg/mL) and PC3 cells (IC50 1.4 and 5.1 µg/mL). Apoptotic assays showed that CEF7, CEF9, CRF6, and CRF5 fractions induced mitochondrial depolarization in A549 cells, 70, 73, 77, and 80%, respectively. Those fractions triggered the apoptosis mitochondrial pathway. CONCLUSION: Our data show that A. subulata extracts have potent antiproliferative properties on human cancer cell lines. This plant should be considered an important source of potent anticancer compounds.

Antimicrobial and Antibiofilm Potential of Flourensia retinophylla against Staphylococcus aureus.

Staphylococcus aureus is a Gram-positive bacteria with the greatest impact in the clinical area, due to the high rate of infections and deaths reaching every year. A previous scenario is associated with the bacteria's ability to develop resistance against conventional antibiotic therapies as well as biofilm formation. The above situation exhibits the necessity to reach new effective strategies against this pathogen. Flourensia retinophylla is a medicinal plant commonly used for bacterial infections treatments and has demonstrated antimicrobial effect, although its effect against S. aureus and bacterial biofilms has not been investigated. The purpose of this work was to analyze the antimicrobial and antibiofilm potential of F. retinophylla against S. aureus. The antimicrobial effect was determined using an ethanolic extract of F. retinophylla. The surface charge of the bacterial membrane, the K+ leakage and the effect on motility were determined. The ability to prevent and remove bacterial biofilms was analyzed in terms of bacterial biomass, metabolic activity and viability. The results showed that F. retinophylla presents inhibitory (MIC: 250 µg/mL) and bactericidal (MBC: 500 µg/mL) activity against S. aureus. The MIC extract increased the bacterial surface charge by 1.4 times and the K+ concentration in the extracellular medium by 60%. The MIC extract inhibited the motility process by 100%, 61% and 40% after 24, 48 and 72 h, respectively. The MIC extract prevented the formation of biofilms by more than 80% in terms of biomass production and metabolic activity. An extract at 10 × MIC reduced the metabolic activity by 82% and the viability by ≈50% in preformed biofilms. The results suggest that F. retinophylla affects S. areus membrane and the process of biofilm formation and removal. This effect could set a precedent to use this plant as alternative for antimicrobial and disinfectant therapies to control infections caused by this pathogen. In addition, this shrub could be considered for carrying out a purification process in order to identify the compounds responsible for the antimicrobial and antibiofilm effect.

In vitro anti-mycobacterial activity of nine medicinal plants used by ethnic groups in Sonora, Mexico.

BACKGROUND: Sonoran ethnic groups (Yaquis, Mayos, Seris, Guarijíos, Pimas, Kikapúes and Pápagos) use mainly herbal based preparations as their first line of medicinal treatment. Among the plants used are those with anti-tuberculosis properties; however, no formal research is available. METHODS: Organic extracts were obtained from nine medicinal plants traditionally used by Sonoran ethnic groups to treat different kinds of diseases; three of them are mainly used to treat tuberculosis. All of the extracts were tested against Mycobacterium tuberculosis H37Rv using the Alamar Blue redox bioassay. RESULTS: Methanolic extracts from Ambrosia confertiflora, Ambrosia ambrosioides and Guaiacum coulteri showed minimal inhibitory concentration (MIC) values of 200, 790 and 1000 µg/mL, respectively, whereas no effect was observed with the rest of the methanolic extracts at the concentrations tested. Chloroform, dichloromethane, and ethyl acetate extracts from Ambrosia confertiflora showed a MIC of 90, 120 and 160 µg/mL, respectively. CONCLUSIONS: A. confertiflora and A. ambrosioides showed the best anti-mycobacterial activity in vitro. The activity of Guaiacum coulteri is consistent with the traditional use by Sonoran ethnic groups as anti-tuberculosis agent.For these reasons, it is important to investigate a broader spectrum of medicinal plants in order to find compounds active against Mycobacterium tuberculosis.

In vitro antioxidant and antiproliferative activities of plants of the ethnopharmacopeia from northwest of Mexico.

BACKGROUND: The aim of this study, is to investigate the in vitro antioxidant activity, the total phenols content, the flavonoids content and the antiproliferative activity of methanolic extracts of the plants: Krameria erecta, Struthanthus palmeri, Phoradendron californicum, Senna covesii and Stegnosperma halimifolium, used by different ethnic groups from northwestern Mexico in the treatment and cure of various diseases. METHODS: The in vitro antioxidant activity was measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing/Antioxidant Power assay (FRAP), the total phenols content was measured by Folin-Ciocalteau assay, the flavonoids content by the AlCl(3) colorimetric method and the antiproliferative activity (line cells HeLa, RAW 264.7, M12A(k).C3.F6 and L929) using MTT method. RESULTS: The K. erecta extract showed the higher radical scavenging activity (67.88%), antioxidant activity by FRAP (1.41 mg Trolox Eq), the highest total phenols content (598.51 mg Galic Acid Eq/g extract), the highest flavonoids content (3.80 mg Quercetin Eq/g extract) and the greatest antiproliferative activity in a dose dependent manner against most Cell line evaluated. A positive correlation was found between the antioxidant activity and the flavonoids content. CONCLUSIONS: This study is the first report on the antioxidant and antiproliferative activities of the five species evaluated. The results demostrate that there is a positive correlation between antioxidant activity and the flavonoids content, indicating that these type of polyphenols could be the major contributors to the observed antioxidant activity in the evaluated plant extracts. Of the extracts evaluated, that of Krameria erecta showed the greatest antioxidant and antiproliferative activities, a discovery that makes this species a promising candidate for future research.

Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract.

Asclepias subulata plant extract has previously demonstrated antiproliferative activity and antimutagenicity against heterocyclic aromatic amines (HAAs) commonly found in cooked meat. The objective of this work was to evaluate the in vitro ability of an ethanolic extract from the medicinal plant Asclepias subulata extract (ASE), non-heated and heated (180 °C), to inhibit the activity of CYP1A1 and CYP1A2, which are largely responsible for HAAs bioactivation. Ethoxyresorufin and methoxyresorufin O-dealkylation assays were performed in rat liver microsomes exposed to ASE (0.002-960 µg/mL). ASE exerted an inhibitory effect in a dose-dependent manner. The half inhibitory concentration (IC50) for unheated ASE was 353.6 µg/mL and 75.9 µg/mL for heated ASE in EROD assay. An IC40 value of 288.4 ± 5.8 µg/mL was calculated for non-heated ASE in MROD assay. However, after heat treatment, the IC50 value was 232.1 ± 7.4 µg/mL. Molecular docking of corotoxigenin-3-O-glucopyranoside, one of the main components of ASE, with CYP1A1/2 structure, was performed. Results show that the interaction of corotoxigenin-3-O-glucopyranoside with CYP1A1/2s' α-helices, which are related with the active site and the heme cofactor, may explain the plant extract's inhibitory properties. Results showed that ASE inhibits CYP1A enzymatic subfamily and may potentially act as a chemopreventive agent by inhibiting bioactivation of promutagenic dietary HAAs.

Biological Activity of Ganoderma Species (Agaricomycetes) from Sonoran Desert, Mexico.

Ganoderma species have been used in folk medicine against different illnesses and are characterized by producing a diversity of bioactive metabolites (triterpenoids, polysaccharides, flavonoids, and phenols) with numerous medicinal effects (anti-proliferative, antioxidant, anti-inflammatory, and antibacterial). This work aims to evaluate ethanolic extracts of fruiting bodies of Ganoderma oerstedii, G. weberianum, and G. subincrustatum strains from the Sonoran Desert in the anti-proliferative activity by the MTT assay on cancer cell lines; anti-inflammatory effect by quantifying nitric oxide (NO) production; antioxidant activity by DPPH, ABTS, and FRAP assays; total phenolic and flavonoid content by Folin-Ciocalteu and AlCl3 method, respectively; antibacterial activity by the broth microdilution method against Escherichia coli and Staphylococcus aureus. Extracts showed anti-proliferative activity with IC50 < 100 µg/mL on the cancer cell lines MDA-MB-231, A549, and HeLa, except G. subincrustatum extract with an IC50 > 100 µg/mL; anti-proliferative activity was not selective, being affected non-cancerous cell line ARPE-19. Extracts showed significant inhibition of NO release in cells stimulated by LPS, up to 60% with G. subincrustatum and G. oerstedii, and 47% with G. weberianum. All tested assays showed moderate antioxidant potential; the most active was G. lucium (control strain) with IC50 of 69 and 30 µg/mL by DPPH and ABTS respectively; and 271 µg Trolox equivalents/g by FRAP. Total phenols and flavonoids ranged from 38 to 56 mg GAE/g and 0.53 to 0.93 mg QE/g, respectively. A significant correlation was found between the antioxidant activities revealed by DPPH, ABTS, and FRAP with total phenol and flavonoid contents. Antibacterial activity was weak against S. aureus (MIC50 > 10 mg/mL). These results demonstrate that tested Ganoderma mushrooms have medicinal potential such as anti-inflammatory and anti-proliferative.

Dogs Detecting COVID-19 From Sweat and Saliva of Positive People: A Field Experience in Mexico.

Context: Molecular tests are useful in detecting COVID-19, but they are expensive in developing countries. COVID-19-sniffing dogs are an alternative due to their reported sensitivity (>80%) and specificity (>90%). However, most of the published evidence is experimental, and there is a need to determine the performance of the dogs in field conditions. Hence, we aimed to test the sensitivity and specificity of COVID-19-sniffing dogs in the field. Methods: We trained four dogs with sweat and three dogs with saliva of COVID-19-positive patients, respectively, for 4.5 months. The samples were obtained from a health center in Hermosillo, Sonora, with the restriction to spend 5 min per patient. We calculated sensitivity, specificity, and their 95% confidence intervals (CI). Results: Two sweat-sniffing dogs reached 76 and 80% sensitivity, with the 95% CI not overlapping the random value of 50%, and 75 and 88% specificity, with the 95% CI not overlapping the 50% value. The 95% CI of the sensitivity and specificity of the other two sweat dogs overlapped the 50% value. Two saliva-sniffing dogs had 70 and 78% sensitivity, and the 95% CI of their sensitivity and specificity did not overlap the 50% value. The 95% CI of the third dog's sensitivity and specificity overlapped the 50% value. Conclusion: Four of the six dogs were able to detect positive samples of patients with COVID-19, with sensitivity and specificity values significantly different from random in the field. We considered the performance of the dogs promising because it is reasonable to expect that with gauze exposed for a longer time to sweat and saliva of people with COVID-19, their detection capacity would improve. The target is to reach the sensitivity range requested by the World Health Organization for the performance of an antigen test (≥80% sensitivity, ≥97% specificity). If so, dogs could become important allies for the control of the COVID-19 pandemic, especially in developing countries.

Casiopeinas® third generation, with indomethacin: synthesis, characterization, DFT studies, antiproliferative activity, and nanoencapsulation.

Seven new Casiopeinas® were synthesized and properly characterized. These novel compounds have a general formula [Cu(N-N)(Indo)]NO3, where Indo is deprotonated indomethacin and N-N is either bipyridine or phenanthroline with some methyl-substituted derivatives, belonging to the third generation of Casiopeinas®. Spectroscopic characterization suggests a square-based pyramid geometry and voltammetry experiments indicate that the redox potential is strongly dependent on the N-N ligand. All the presented compounds show high cytotoxic efficiency, and most of them exhibit higher efficacy compared to the well-known cisplatin drug and acetylacetonate analogs of the first generation. Computational calculations show that antiproliferative behavior can be directly related to the volume of the molecules. Besides, a chitosan (CS)-polyacrylamide (PNIPAAm) nanogel was synthesized and characterized to examine the encapsulation and release properties of the [Cu(4,7-dimethyl-1,10-phenanthroline)(Indo)]NO3 compound. The results show good encapsulation performance in acidic conditions and a higher kinetic drug release in acidic media than at neutral pH. This result can be described by the Peppas-Sahlin model and indicates a release mechanism predominantly by Fick diffusion.

Association of Different ABO and Rh Blood Groups with the Erythroprotective Effect of Extracts from Navicula incerta and Their Anti-Inflammatory and Antiproliferative Properties.

Previous studies have reported that different blood groups are associated with the risk of chronic degenerative diseases that mainly involve inflammation and neoplastic processes. We investigate the relationship between blood groups and the erythroprotective effect of extracts from Navicula incerta against oxidative damage as a proposal to develop drugs designed for people with a specific blood type related to chronic pathology. The study was carried out through the elucidation of the erythroprotective potential, anti-inflammatory and antiproliferative activity of Navicula incerta. Research suggests that the presence or absence of certain blood groups increases or decreases the abilities of certain phytochemicals to inhibit oxidative stress, which is related to the systemic inflammatory response involved in the development of different types of cancer. The pigment-rich extracts from Navicula incerta inhibit ROO•- induced oxidative stress in human erythrocytes on the A RhD+ve antigen without compromising the structure of the cell membrane. This result is very important, since the A antigen is related to the susceptibility of contracting prostate cancer. Similarly, it was possible to inhibit the proliferation of cervical (HeLa) and prostate (PC-3) carcinoma. The combinatorial analysis of different biological activities can help design phytochemicals as new candidates for preventive drugs treating the chronic degenerative diseases associated with a specific blood group.

Antiproliferative activity of standardized herbal phytopreparation from Asclepias subulata.

Background: Several studies have shown that active compounds of Asclepias subulata (cardenolides) have antiproliferative effect on human cancer cells. Cardenolides isolated from A. subulata can be used as active chemical markers to elaborate phytopharmaceutical preparations. To evaluate the antiproliferative effect of a standardized extract of the aerial parts, based on Asclepias subulata cardenolides. Methods: Four standardized extracts were prepared by HPLC-DAD depending on the concentration of calotropin and the antiproliferative activity was measured for the MTT assay, on the A549, MCF-7, HeLa, PC3 and ARPE cell lines. The concentrations of calotropin used for the standardization of the extracts were 10, 7.6, 5 and 1 mg/dL. Results: Standardization of the A. subulata extract based on calotropin at 7.6 mg/g dry weight was achieved and the antiproliferative activity was evaluated over A549, HeLa and MCF-7 cell lines, obtaining proliferation percentages of 3.8 to 13.4% . Conclusions: The standardized extracts of A. subulata at different concentrations of calotropin showed antiproliferative activity against all the cell lines evaluated. The greatest effect was observed against the HeLa cell line.

[Hospital and community-acquired ß-lactamases-producing Escherichia coli and Klebsiella pneumoniae at hospitals in Hermosillo, Sonora]. / Escherichia coli y Klebsiella pneumoniae comunitarias y hospitalarias productoras de ß-lactamasas en hospitales de Hermosillo, Sonora.

OBJECTIVE: To determine the prevalence of extended-spectrum ß-lactamases (ESBL)-producing Esherichia coli and Klebsiella pneumoniae in hospitals of Hermosillo, Sonora, Mexico. MATERIAL AND METHODS: To detect ESBL-production, 1 412 bacterial isolates obtained over a one year period (2008-2009) were analyzed using the double-disk synergy test, with and without clavulanic acid. RESULTS: Hospitalaryacquired ESBL-producing E.coli and K.pneumoniae (31.8% and 35.3%) were isolated with higher prevalence that community-acquired isolates (14.4% and 0.0%) (p<0.005). CONCLUSIONS: Our study shows the presence of ESBL-producing bacteria in the three hospitals.

"Immunoinformatic Identification of T-Cell and B-Cell Epitopes From Giardia lamblia Immunogenic Proteins as Candidates to Develop Peptide-Based Vaccines Against Giardiasis".

Giardiasis is one of the most common gastrointestinal infections worldwide, mainly in developing countries. The etiological agent is the Giardia lamblia parasite. Giardiasis mainly affects children and immunocompromised people, causing symptoms such as diarrhea, dehydration, abdominal cramps, nausea, and malnutrition. In order to develop an effective vaccine against giardiasis, it is necessary to understand the host-Giardia interactions, the immunological mechanisms involved in protection against infection, and to characterize the parasite antigens that activate the host immune system. In this study, we identify and characterize potential T-cell and B-cell epitopes of Giardia immunogenic proteins by immunoinformatic approaches, and we discuss the potential role of those epitopes to stimulate the host´s immune system. We selected the main immunogenic and protective proteins of Giardia experimentally investigated. We predicted T-cell and B-cell epitopes using immunoinformatic tools (NetMHCII and BCPREDS). Variable surface proteins (VSPs), structural (giardins), metabolic, and cyst wall proteins were identified as the more relevant immunogens of G. lamblia. We described the protein sequences with the highest affinity to bind MHC class II molecules from mouse (I-Ak and I-Ad) and human (DRB1*03:01 and DRB1*13:01) alleles, as well as we selected promiscuous epitopes, which bind to the most common range of MHC class II molecules in human population. In addition, we identified the presence of conserved epitopes within the main protein families (giardins, VSP, CWP) of Giardia. To our knowledge, this is the first in silico study that analyze immunogenic proteins of G. lamblia by combining bioinformatics strategies to identify potential T-cell and B-cell epitopes, which can be potential candidates in the development of peptide-based vaccines. The bioinformatics analysis demonstrated in this study provides a deeper understanding of the Giardia immunogens that bind to critical molecules of the host immune system, such as MHC class II and antibodies, as well as strategies to rational design of peptide-based vaccine against giardiasis.

The Dichloromethane Fraction of Croton sonorae, A Plant Used in Sonoran Traditional Medicine, Affect Entamoeba histolytica Erythrophagocytosis and Gene Expression.

Intestinal parasites are a global problem, mainly in developing countries. Obtaining information about plants and compounds that can combat gastrointestinal disorders and gastrointestinal symptoms is a fundamental first step in designing new treatment strategies. In this study, we analyzed the antiamoebic activity of the aerial part of Croton sonorae. The dichloromethane fraction of C. sonorae (CsDCMfx) contained flavonoids, terpenes, alkaloids, and glycosides. The ultrastructural morphology of the amoebae treated for 72 h with CsDCMfx was completely abnormal. CsDCMfx reduced erythrophagocytosis of trophozoites and the expression of genes involved in erythrocyte adhesion (gal/galnac lectin) and actin cytoskeleton rearrangement in the phagocytosis pathway (rho1 gtpase and formin1). Interestingly, CsDCMfx decreased the expression of genes involved in Entamoeba histolytica trophozoite pathogenesis, such as cysteine proteases (cp1, cp4, and cp5), sod, pfor, and enolase. These results showed that C. sonorae is a potential source of antiamoebic compounds.