HPV infection as a risk factor for atherosclerosis: A connecting hypothesis.

Atheromatous plaques occurring in large arteries are common and life-threatening lesions. Multiple factors are involved in the pathogenesis of atheromatous plaques, such as hyperlipidaemia and hypercholesterolaemia, high blood pressure and chronic systemic inflammation. Recent findings have suggested that infection with high-risk human papillomavirus (HPV) may increase the risk of developing atheromatous plaques. However, HPV is considered a tissue-specific virus with a strong tropism towards squamous epithelial cells, and the mechanisms whereby it may promote the development of atheromas remain unclear. Here, we propose a connecting hypothesis to explain the possible causative role of HPV on atheroma development. We hypothesize that HPV infection may promote atheroma formation in infected patients by enhancing systemic inflammation or by directly targeting blood vessels via nucleic acids carried by extracellular vesicles such as exosomes. The pro-inflammatory effects of HPV and the release of extracellular vesicles by HPV-transformed cells are well documented in scientific literature. Possible experimental approaches to test this hypothesis are also discussed, especially experiments employing transgenic mice bearing HPV16 transgenes. If correct, this hypothesis would have major implications for the prevention of cardiovascular diseases, especially due to the preventable nature of HPV infection through vaccination.

Repurposing strategies for Chagas disease therapy: the effect of imatinib and derivatives against Trypanosoma cruzi.

Chagas disease (CD) is a neglected parasitic condition endemic in the Americas caused by Trypanosoma cruzi. Patients present an acute phase that may or not be symptomatic, followed by lifelong chronic stage, mostly indeterminate, or with cardiac and/or digestive progressive lesions. Benznidazole (BZ) and nifurtimox are the only drugs approved for treatment but not effective in the late chronic phase and many strains of the parasite are naturally resistant. New alternative therapy is required to address this serious public health issue. Repositioning and combination represent faster, and cheaper trial strategies encouraged for neglected diseases. The effect of imatinib (IMB), a tyrosine kinase inhibitor designed for use in neoplasias, was assessed in vitro on T. cruzi and mammalian host cells. In comparison with BZ, IMB was moderately active against different strains and forms of the parasite. The combination IMB + BZ in fixed-ratio proportions was additive. Novel 14 derivatives of IMB were screened and a 3,2-difluoro-2-phenylacetamide (3e) was as potent as BZ on T. cruzi but had low selectivity index. The results demonstrate the importance of phenotypic assays, encourage the improvement of IMB derivatives to reach selectivity and testify to the use of repurposing and combination in drug screening for CD.

Laurus nobilis (laurel) aqueous leaf extract's toxicological and anti-tumor activities in HPV16-transgenic mice.

Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16-/- without treatment, group II: treated HPV16-/-, group III: HPV16+/- without treatment and group IV: treated HPV16+/-). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wild-type animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers.

Ozone therapy prevents the onset of dysplasia in HPV16-transgenic mice-A pre-clinical efficacy and safety analysis.

Infection with high-risk human papillomavirus (HPV), most often HPV16, is associated with the development of anogenital and oropharyngeal cancers. Recently, ozone therapy was reported to have considerable efficacy against rabbit VX2 tumors, induced by the cottontail rabbit papillomavirus. The present study aims to determine whether similar results can be obtained in HPV16-transgenic mice, possibly paving the way for new therapeutic options against HPV-induced cancers. HPV16-transgenic and wild-type, female, 20 weeks-old mice were injected intraperitoneally with medical O3/O2 (80░mL/kg, at O3 50░µg/mL), once a day, for 5 consecutive days. The animals were sacrificed at 25 weeks-old, and skin samples were analyzed histologically to study tumour progression. Blood and internal organ samples were used to study toxicological parameters. 85.7% of untreated transgenic mice showed dysplastic skin lesions, compared with 28.6% of O3-treated mice. This was associated with a marked reduction of dermal inflammation associated with those lesions. No significant changes were observed in any toxicological parameters. These preliminary results support the hypothesis that O3 therapy is effective against papillomavirus-induced lesions, particularly against those induced by the most common high-risk virus, HPV16. Further studies are needed to confirm the mechanisms underlying these effects.

Phytochemical profiling as a solution to palliate disinfectant limitations.

The indiscriminate use of biocides for general disinfection has contributed to the increased incidence of antimicrobial tolerant microorganisms. This study aims to assess the potential of seven phytochemicals (tyrosol, caffeic acid, ferulic acid, cinnamaldehyde, coumaric acid, cinnamic acid and eugenol) in the control of planktonic and sessile cells of Staphylococcus aureus and Escherichia coli. Cinnamaldehyde and eugenol showed antimicrobial properties, minimum inhibitory concentrations of 3-5 and 5-12 mM and minimum bactericidal concentrations of 10-12 and 10-14 mM against S. aureus and E. coli, respectively. Cinnamic acid was able to completely control adhered bacteria with effects comparable to peracetic acid and sodium hypochlorite and it was more effective than hydrogen peroxide (all at 10 mM). This phytochemical caused significant changes in bacterial membrane hydrophilicity. The observed effectiveness of phytochemicals makes them interesting alternatives and/or complementary products to commonly used biocidal products. Cinnamic acid is of particular interest for the control of sessile cells.

Bracken-associated human and animal health hazards: chemical, biological and pathological evidence.

Bracken (Pteridium aquilinum) is a widely distributed carcinogenic fern, to whose toxins human populations are exposed through multiple routes. Animals are also affected by bracken toxins, leading to serious production losses yearly. Accordingly, several governmental reports regarding the safeguard of public health against bracken carcinogens have been recently issued. This review describes the main bioactive compounds identified in bracken and their biological effects at the molecular, cellular, pathological and populational levels, with particular emphasis on ptaquiloside, the main bracken carcinogen. Recent biopathological studies shedding further light on the genotoxicity immunotoxicity and carcinogenicity of ptaquiloside are discussed. Key steps on the long effort to understand bracken toxicology are also reviewed, along with the latest findings on new bracken toxins and human exposures routes. The presence of ptaquiloside and related terpene glycosides in milk, meat and water are of particular concern from the viewpoints of both human and animal health.

Biofouling control using microparticles carrying a biocide.

This study presents a new technological approach to minimize the use of antimicrobial (AMB) agents and their deleterious effects, based on the principle of drug-delivery systems whereby the AMB chemicals are transported on microparticles. The efficacy of microparticles carrying the quaternary ammonium compound (QAC), benzyldimethyldodecyl ammonium chloride (BDMDAC), was assessed against Pseudomonas fluorescens in both the planktonic and the biofilm state. The microparticles were prepared using a layer-by-layer (LBL) self-assembly technique. Oppositely charged molecules of polyethyleneimine (PEI), sodium polystyrene sulfonate (PSS), and BDMDAC were assembled on polystyrene (PS) cores. BDMDAC-coated particles were observed by CryoSEM and their composition analyzed by X-ray microanalysis. Zeta potential measurements indicated that changes in surface charge were compatible with a BDMDAC/particle interaction. This biocidal carrier structure had significant stability, verified by the release of only 15% of the BDMDAC when immersed in water for 18 months. Biocidal carrier activity was evaluated by determining the survival ratio of P. fluorescens planktonic and biofilm cells after different exposure periods to BDMDAC-coated particles. Tests with biofilm cells were also performed with the free QAC. An efficient AMB effect (minimum bactericidal concentration) against suspended cells was found for a concentration of 9.2 mg l(-1) of BDMDAC on coated particles after incubation for 30 min and 6.5 mg l(-1) of BDMDAC on coated particles after 60 min. Exposure of biofilms to PS-PEI/PSS/BDMDAC (0.87 mg l(-1)) resulted in a decrease in viability of 60.5% and 66.5% of the total biofilm population for 30 and 60 min exposure times, respectively. Exposure for 60 min to 6.33 mg l(-1) and 11.75 mg l(-1) of BDMDAC in PS-PEI/PSS/BDMDAC particles promoted inactivation of 80.6% and 87.2% of the total population, respectively. The AMB effects obtained with the application of free BDMDAC were statistically similar to those promoted by the application of BDMDAC coated particles. The overall results indicate that this novel AMB strategy has potential for the control of microbial growth of planktonic cells and biofouling. Moreover, the technique allows the reuse of AMB molecules and consequently reduces the environmental risks associated with excessive use of AMB agents, thereby providing real benefits to public health.

Lignans and Other Constituents of Centaurea sphaerocephala ssp. polyacantha.

Extraction of the aerial parts of CENTAUREA SPHAEROCEPHALA L. ssp. POLYACANTHA (Willd.) Dostal furnished the lignans (-)-matairesinol, (-)-arctigenin, and (-)-arctiin, two sesquilignans lappaol A and a stereo- or structural isomer of lappaol A, and a new dithienylacetylene.