The Interplay between Medical Plants and Gut Microbiota in Cancer.

The gut microbiota is a dynamic community of bacteria distributed in the gastroenteric tract and changes in response to diseases, diet, use of antibiotics and probiotics, hygiene status, and other environmental factors. Dysbiosis, a disruption of the normal crosstalk between the host and the microbes, is associated with obesity, diabetes, cancer, and cardiovascular diseases, is linked to a reduction of anti-inflammatory bacteria like Lactobacillus and Roseburia, and to an increase in the growth of proinflammatory species like Ruminococcus gnavus and Bacteroidetes. Some plants possess anticancer properties and various studies have reported that some of these are also able to modulate the gut microbiota. The aim of this work is to evaluate the crucial relationship between medical plants and gut microbiota and the consequences on the onset and progression of cancer. In vivo studies about hematological malignancies showed that beta-glucans tie to endogenous antibeta glucan antibodies and to iC3b, an opsonic fragment of the central complement protein C3, leading to phagocytosis of antibody-targeted neoplastic cells and potentiation of the cytotoxic activity of the innate immune system if administered together with monoclonal antibodies. In conclusion, this review suggests the potential use of medical plants to improve gut dysbiosis and assist in the treatment of cancer.

Evaluation of cadmium and arsenic effects on wild and cultivated cardoon genotypes selected for metal phytoremediation and bioenergy purposes.

Cynara cardunculus L. is a multipurpose crop, characterized by high production of biomass suitable for energy purposes and green chemistry. Taking advantage of its already demonstrated ability to grow in polluted environments that characterize many world marginal lands, the aim of this work was to investigate the response of different cardoon genotypes to exposure to cadmium (Cd) and arsenic (As) pollution, in order to use this crop for rehabilitation of contaminated sites and its biomass for energy production. In this study, seeds of two wild cardoon accessions harvested in rural and industrial Sicilian areas and of a selected line of domestic cardoon were used, and the grown plants were spiked with As and Cd, alone or in combination, at two different concentrations (500 and 2000 µM) and monitored for 45 days. The growth parameters showed that all the plants survived until the end of experiment, with growth stimulation in the presence of low concentrations of As and Cd, relative to metal-free controls. Biomass production was mostly allocated in the roots in As treatment and in the shoots in Cd treatment. Cd EXAFS analysis showed that tolerance to high concentrations of both metals was likely linked to complexation of Cd with oxygen-containing ligands, possibly organic acids, in both root and leaf biomass with differences in behaviour among genotypes. Under As+Cd contamination, the ability of the plants to translocate As to aboveground system increased also showing that, for both metal(loid)s, there were significant differences between genotypes studied. Moreover, the results showed that Cynara cardunculus var. sylvestris collected in an industrial area is the genotype that, among those studied, had the best phytoextraction capability for each metal(loid).

MYB5-like and bHLH influence flavonoid composition in pomegranate.

The fruit of the pomegranate (Punica granatum L.) is an important nutraceutical food rich in polyphenolic compounds, including hydrolysable tannins, anthocyanins and flavonols. Their composition varies according to cultivar, tissue and fruit development stage and is probably regulated by a combination of MYB and bHLH type transcription factors (TFs). In this study, metabolomics analysis during fruit developmental stages in the main pomegranate cultivars, Wonderful and Valenciana with contrasting colour of their ripe fruits, showed that flavonols were mostly present in flowers while catechins were highest in unripe fruits and anthocyanins in late fruit maturation stages. A novel MYB TF, PgMYB5-like, was identified, which differs from previously isolated pomegranate TFs by unique C-terminal protein motifs and lack of the amino-acid residues conserved among anthocyanins promoting MYBs. In both pomegranate cultivars the expression of PgMYB5-like was high at flowering stage, while it decreased during fruit ripening. A previously identified bHLH-type TF, PgbHLH, also showed high transcript levels at flowering stage in both cultivars, while it showed a decrease in expression during fruit ripening in cv. Valenciana, but not in cv. Wonderful. Functional analysis of both TFs was performed by agro-infiltration into Nicotiana benthamiana leaves. Plants infiltrated with the PgMYB5-like+PgbHLH combined construct showed a specific and significant accumulation of intermediates of the flavonoid pathway, especially dihydroflavonols, while anthocyanins were not produced. Thus, we propose a role for PgMYB5-like and PgbHLH in the first steps of flavonoid production in flowers and in unripe fruits. The expression patterns of these two TFs may be key in determining the differential flavonoid composition in both flowers and fruits of the pomegranate varieties Wonderful and Valenciana.

A Proinflammatory Immune Response Might Determine Toxoplasma gondii Vertical Transmission and Severity of Clinical Features in Congenitally Infected Newborns.

Toxoplasma gondii is the etiological agent of toxoplasmosis. Mother-to-child transmission of this parasite can occur during pregnancy. Newborns with congenital toxoplasmosis may develop central nervous system impairment, with severity ranging from subclinical manifestations to death. A proinflammatory/regulated specific immune profile is crucial in the defense against the parasite; nevertheless, its role in the infected pregnant women and the congenitally infected offspring has been poorly explored, and there is still no consensus about its relation to parasite vertical transmission or to severity and dissemination in the congenitally infected newborns. This work aimed to characterize these relations by means of principal component and principal factor analyses. For this purpose, we determined the specific production of the four immunoglobulin G antibody subclasses, cytokines, and lymphocyte proliferation in the T. gondii-infected pregnant women-10 who transmitted the infection to their offspring and seven who did not-as well as in 11 newborns congenitally infected and grouped according to disease severity (five mild and six moderate/severe) and dissemination (four local and seven disseminated). We found that the immune response of nontransmitter women differed from that of the transmitters, the latter having a stronger proinflammatory response, supporting a previous report. We also found that newborns who developed moderate/severe disease presented higher levels of lymphocyte proliferation, particularly of CD8+ and CD19+ cells, a high proportion of tumor necrosis factor α producers, and reduced expression of the immune modulator transforming growth factor ß, as opposed to children who developed mild clinical complications. Our results suggest that a distinctive, not regulated, proinflammatory immune response might favor T. gondii vertical transmission and the development of severe clinical manifestations in congenitally infected newborns.

Tratamiento de infección crónica por virus de hepatitis C en niños, ¿perspectiva hacia la curación o lejos de la meta? / Treatment of chronic hepatitis C virus infection in children, prospect towards cure or far from the goal?

Resumen La infección por el virus de hepatitis C es un problema global de salud pública; en México aproximadamente 2 % de la población se encuentra infectada. En niños, los datos de prevalencia son variables según la edad, pero se estima que 0.1 a 2 % de los niños presenta infección crónica por virus de hepatitis C, cuya principal vía de transmisión es la perinatal. Actualmente existen antivirales de acción directa aprobados en adultos con una tasa de respuesta viral sostenida superior a 95 %; sin embargo, en niños aún son pocos los estudios que confirman su seguridad y efectividad. Aunque todavía estamos lejos de la meta, avanzamos rápidamente hacia un tratamiento óptimo de curación también para pacientes pediátricos.

Abstract Infection with hepatitis C virus is a global health problem; in Mexico, approximately 2% of the population is infected. In children, data on prevalence are variable according to the age group, but 0.1-2% of children are estimated to have chronic infection with hepatitis C virus, the main way of transmission of which is perinatal. Currently, there are direct-acting antiviral agents approved in adults that offer a sustained viral response rate higher than 95%; however, in children there are still only few studies confirming their safety and effectiveness. Although we are still far from the goal, we are rapidly advancing towards an optimal curative treatment also for pediatric patients.

Report of an unsual case of anophthalmia and craniofacial cleft in a newborn with Toxoplasma gondii congenital infection.

BACKGROUND: We present one unusual case of anophthalmia and craniofacial cleft, probably due to congenital toxoplasmosis only. CASE PRESENTATION: A two-month-old male had a twin in utero who disappeared between the 7th and the 14th week of gestation. At birth, the baby presented anophthalmia and craniofacial cleft, and no sign compatible with genetic or exposition/deficiency problems, like the Wolf-Hirschhorn syndrome or maternal vitamin A deficiency. Congenital toxoplasmosis was confirmed by the presence of IgM abs and IgG neo-antibodies in western blot, as well as by real time PCR in blood. CMV infection was also discarded by PCR and IgM negative results. Structures suggestive of T. gondii pseudocysts were observed in a biopsy taken during the first functional/esthetic surgery. CONCLUSIONS: We conclude that this is a rare case of anophthalmia combined with craniofacial cleft due to congenital toxoplasmosis, that must be considered by physicians. This has not been reported before.

Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM).

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary. In the last few years, pomegranate has been studied for its potential therapeutic properties including treatment and prevention of cancer. Pomegranate juice (PGJ) contains a number of potential active compounds including organic acids, vitamins, sugars, and phenolic components that are all responsible of the pro-apoptotic effects observed in tumor cell line. The aim of present investigation is to assess the antiproliferative and antiangiogenic potential of the PGJ in human multiple myeloma cell lines. Our data demonstrate the anti-proliferative potential of PGJ in MM cells; its ability to induce G0/G1 cell cycle block and its anti-angiogenic effects. Interestingly, sequential combination of bortezomib/PGJ improved the cytotoxic effect of the proteosome inhibitor. We investigated the effect of PGJ on angiogenesis and cell migration/invasion. Interestingly, we observed an inhibitory effect on the tube formation, microvessel outgrowth aorting ring and decreased cell migration and invasion as showed by wound-healing and transwell assays, respectively. Analysis of angiogenic genes expression in endothelial cells confirmed the anti-angiogenic properties of pomegranate. Therefore, PGJ administration could represent a good tool in order to identify novel therapeutic strategies for MM treatment, exploiting its anti-proliferative and anti-angiogenic effects. Finally, the present research supports the evidence that PGJ could play a key role of a future therapeutic approach for treatment of MM in order to optimize the pharmacological effect of bortezomib, especially as adjuvant after treatment.