Genotoxicity, cytotoxicity and toxicological evaluation of whole plant extracts of the medicinal plant Phyllanthus niruri (Phyllanthaceae)

Phyllanthus niruri is a medicinal plant (commonly known as stone breaker) found in the tropics and other parts of the world. It is known for its capacity to block the formation of calcium oxalate crystals and kidney stone formation in urolithiasis. This plant has been used to treat hyperglycemia, hypertension, pain, and mild cases of malaria. We examined the geno-, cyto- and overall toxicity of P. niruri whole plant ethanolic extract. The extract was administered as a single dose of 30 or 300 mg/kg to laboratory rats by gavage, accompanied by negative (0.9% saline) and positive (10 mg/mL N-ethyl-N-nitrosourea) controls that were injected intramuscularly 48 h after extract administration. The ratio of polychromatic (PCE)/normochromatic erythrocytes (NCE) from femur bone marrow was scored for genotoxicity. Cytotoxicity was determined using descending concentrations (0.2-0.0125 g/mL) of the extract incubated with peripheral blood mononuclear cells. Lactate dehydrogenase release from damaged cells was determined and the CC(50) calculated. Subchronic administration of the extract at 30 or 300 mg/kg was done for 90 days to determine general toxicity. PCE:NCE (%) for the extract and negative control was 63, compared to 168 (positive control). The CC(50) was 26.3 mg/mL and hepato-renal toxicity after subchronic extract administration was nil. We conclude that ethanol extract of P. niruri is not cytotoxic or genotoxic, and is generally non-toxic on subchronic administration.     

Evaluating Farmers’ Knowledge of Shade Trees in Different Cocoa Agro-Ecological Zones in Ghana

Shade trees are an integral part of most cocoa growing systems across the world. This study assesses farmers’ local knowledge of shade trees at two locations in Ghana with different climatic conditions and vulnerability to climate change. Akumadan is located in the northern dry part of the cocoa belt representing marginal conditions for cocoa cultivation, whereas Asankragua is located in the southern wet part, more ecologically favorable for cocoa cultivation. Inventories were conducted to assess the abundance of species, their structural characteristics and benefits to cocoa systems. Results show that cocoa farmers have detailed knowledge on the functions of shade trees in cocoa systems and prefer species that provide specific needs according to the location. However, abundance of species in a location does not necessary translate into beneficial impacts on cocoa productivity. In the drier part of the cocoa belt, income diversification through shade trees is an adaptation strategy to the increasingly marginal conditions for cocoa production, which has led to the high proportion of fruit trees among the most abundant species. In contrast, farmers in the southern part of the cocoa belt select shade trees for their high cocoa compatibility. Adaptation strategies for cocoa farmers should therefore promote species that best accommodate farmers’ economic, agronomic and environmental needs.     

Nitric oxide exposure of CC531 rat colon carcinoma cells induces gamma-glutamyltransferase which may counteract glutathione depletion and cell death

Gamma-glutamyltransferase (GGT) has a central role in glutathione homeostasis by initiating the breakdown of extracellular GSH. We investigated in the present study whether nitric oxide exposure of CC531 rat colon carcinoma cells modulates GGT and how the activity of the enzyme affects the level of intracellular GSH. The data show that GGT activity was induced in a dose-related manner by two NO-donors (spermineNONOate and nitrosoglutathione) and that antioxidants partly inhibited the induction. SpermineNONOate lowered intracellular GSH and induced apoptosis. Cultivating the cells in cystine-depleted medium also resulted in a 50% lowering of GSH, but this was avoided when GSH was added to the medium. This effect was mediated by the activity of GGT and shown after inhibiting GGT activity with acivicin and cyst(e)ine transporters with alanine and homocysteic acid. This shows that the cells benefit from GGT in maintaining the intracellular GSH level. Cells with induced GGT activity obtained after NO incubation showed a higher uptake rate of cysteine (2-fold), measured by incubating the cells with 5S-radiolabeled GSH. The enzyme was also induced by interferon-gamma and tumor necrosis factor-alpha, but this induction was not connected to activation of the endogenous nitric oxide synthase, as the addition of aminoguanidine, a NO-synthase inhibitor, did not affect the induction. The present study shows that the activity of GGT is upregulated by NO-donors and that the colon carcinoma cells, when cultivated in cystine-depleted medium, benefit from the enzyme in maintaining the intracellular level of GSH. Thus, the enzyme will add to the protective measures of the tumor cells during nitrosative stress.     

Putative type 1 thymidylate synthase and dihydrofolate reductase as signature genes of a novel bastille-like group of phages in the subfamily Spounavirinae

Background

Spounavirinae viruses have received an increasing interest as tools for the control of harmful bacteria due to their relatively broad host range and strictly virulent phenotype.

Results

In this study, we collected and analyzed the complete genome sequences of 61 published phages, either ICTV-classified or candidate members of the Spounavirinae subfamily of the Myoviridae. A set of comparative analyses identified a distinct, recently proposed Bastille-like phage group within the Spounavirinae. More importantly, type 1 thymidylate synthase (TS1) and dihydrofolate reductase (DHFR) genes were shown to be unique for the members of the proposed Bastille-like phage group, and are suitable as molecular markers. We also show that the members of this group encode beta-lactamase and/or sporulation-related SpoIIIE homologs, possibly questioning their suitability as biocontrol agents.

Conclusions

We confirm the creation of a new genus—the “Bastille-like group”—in Spounavirinae, and propose that the presence of TS1- and DHFR-encoding genes could serve as signatures for the new Bastille-like group. In addition, the presence of metallo-beta-lactamase and/or SpoIIIE homologs in all members of Bastille-like group phages makes questionable their suitability for use in biocontrol.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1757-0) contains supplementary material, which is available to authorized users.     

Realizing Three‐Electron Redox Reactions in NASICON‐Structured Na3MnTi(PO4)3 for Sodium‐Ion Batteries

Developing multielectron reaction electrode materials is essential for achieving high specific capacity and high energy density in secondary batteries; however, it remains a great challenge. Herein, Na₃MnTi(PO₄)₃/C hollow microspheres with an open and stable NASICON framework are synthesized by a spray‐drying‐assisted process. When applied as a cathode material for sodium‐ion batteries, the resultant Na₃MnTi(PO₄)₃/C microspheres demonstrate fully reversible three‐electron redox reactions, corresponding to the Ti^3+/4+ (≈2.1 V), Mn^2+/3+ (≈3.5 V), and Mn^3+/4+ (≈4.0 V vs Na⁺/Na) redox couples. In situ X‐ray diffraction results reveals that both solid‐solution and two‐phase electrochemical reactions are involved in the sodiation/desodiation processes. The high specific capacity (160 mAh g^?1 at 0.2 C), outstanding cyclability (≈92% capacity retention after 500 cycles at 2 C), and the facile synthesis make the Na₃MnTi(PO₄)₃/C a prospective cathode material for sodium‐ion batteries.     

Serum Levels of Cu,Se, and Zn in Adult Rural/Urban Residents in Ghana: Paradigm Shift?

Deficiencies in Cu, Se, and Zn impair one or more biochemical functions, and excess are associated with toxicity. Baseline studies on the Ghanaian population are scanty. The study was undertaken to determine whether significant rural/urban differences in the serum levels of Cu, Se, and Zn did exist. Forty males/60 females from rural and 50 males/50 females from urban Ghanaian communities were sampled. Serum Cu, Se, and Zn were determined using flame atomic absorption spectrometry. Cu level for rural and urban subjects was 997 ± 333 and 979 ± 290 μg/L, respectively (p = 0.68). However, Cu levels were significantly higher in the rural females (1,063 ± 367 μg/L) than the rural males (898 ± 249 μg/L; p = 0.0085). Se levels for rural/urban subjects were 97 ± 36 and 87 ± 31 μg/L, respectively (p = 0.03). Zn levels in the rural/urban subjects were 312 ± 218 and 150 ± 102 μg/L, respectively (p = 0.002). Additionally, Zn was significantly higher in rural females (428 ± 204 μg/L) than the urban females (166 ± 103 μg/L; p = 0.0002). Finally, Zn was significantly higher in rural females (428 ± 204 μg/L) than males (172 ± 116 μg/L; p = 0.0028). In conclusion, Cu, Se, and Zn were higher in the rural group compared to the urban group, and the generally low Zn levels were confirmed in another cohort follow-up study.     

Plasma interleukin-1β concentration is associated with stroke in sickle cell disease

The pathogenesis of sickle cell disease (HbSS), which has numerous complications including stroke, involves inflammation resulting in alteration of plasma inflammatory protein concentration. We investigated HbSS children with abnormal cerebral blood flow detected by trans-cranial Doppler ultrasound (TCD) who participated in the multi-center stroke prevention (STOP) study, to determine if plasma inflammatory protein concentration is associated with the outcome of stroke. Thirty-nine plasma samples from HbSS participants with elevated TCD who had no stroke, HbSS-NS (n = 13) or had stroke, HbSS-S (n = 13), HbSS steady-state controls (n = 7) and controls with normal hemoglobin, HbAA (n = 6), were analyzed simultaneously for 27 circulating inflammatory proteins. Logistic regression and receiver operating characteristics curve analysis of stroke on plasma inflammatory mediator concentration, adjusted for age and gender, demonstrated that interleukin-1β (IL-1β) was protective against stroke development (HbSS-NS = 19, 17–23, HbSS-S = 17, 16–19 pg/mL, median and 25th–75th percentile; odds ratio = 0.59, C.I. = 0.36–0.96) and was a good predictor of stroke (area under curve = 0.852). This result demonstrates a strong association of systemic inflammation with stroke development in HbSS via moderately increased plasma IL-1β concentration, which is furthermore associated with a decreased likelihood of stroke in HbSS.