Alterations of antitumor and metabolic responses in L5178Y-R lymphoma-bearing mice after only 30-minute daily chronic stress exposure

Aim: In stress research, reducing times of stress induction may contribute to improving the well-being of experimental animals, especially in cancer models, already under physiological distress. To support this idea, we evaluated the effects of a short-timed stress protocol on endocrine, metabolic and immune indicators in mice bearing the L5178Y-R lymphoma. Materials and Methods: A 30-minute daily stress protocol was applied for 28 days to healthy and lymphoma-bearing BALB/c mice; body weight, plasma levels of corticosterone, norepinephrine, Th1/Th2 cytokines, insulin, and leptin, were measured. Results: We found a 12% significant decrease in body weight in non-tumor bearing mice under stress (p < 0.007). The disruption of weight evolution was accompanied by a stress induced 85% decrease in plasmatic leptin (p < 0.01) and total reduction of insulin. Tumor burden alone was associated to an increase in more than two-fold of plasmatic levels of norepinephrine (p < 0.008). Neither stress nor tumor or their combination, resulted in an elevation of systemic IL-6. IFN-γ levels were 20 times higher in lymphoma-bearing animals when compared with non-tumor bearing mice (p < 0.01); however, under stress, this response was reduced by half, indicating a suppressing effect of chronic stress on the antitumor immune response. Conclusion: A short-timed stress induction is enough to cause significant alterations in the metabolism and immunity of healthy and tumor-bearing mice, supporting the use of short-timed protocols as an efficient way to induce chronic stress that also considers concerns regarding the well-being of experimental animals in biomedical research

In Vitro Murine Lymphoma L5178y-R Cells Growth Inhibition By Endophytic Fungi Isolated From Lophocereus Marginatus

Background: Chemotherapy is one of the main treatments to fight cancer. However, about 90% of failures in this procedure are due to the invasion and metastasis of drug-resistant cancer cells. Therefore, the search for new drugs has become critical in oncology. Endophytic fungi, as important sources of bioactive compounds, represent an alternative for the isolation, characterization, and development of new pharmacological treatments for cancer control. The aim of the present study was to evaluate the cytotoxic activity of liquid culture extracts of endophytic fungi isolated from Lophocereus marginatus against murine lymphoma L5178Y-R cells. Methods: Endophytic fungi obtained from L. marginatus stems were isolated and morphologically characterized. Aqueous, methanolic, and ethyl acetate extracts were obtained from fungal liquid cultures. To evaluate the anticancer activity, we used tumor L5178Y-R cells and control peripheral blood mononuclear cells (PBMCs). Extracts were evaluated at 250 and 25 µg/mL and 250 µg/mL, using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide) colorimetric reduction assay to determine cytotoxicity. Vincristine and 1% DMSO were used as positive and negative controls, respectively. The IC50 value and selectivity index (SI) were determined only for the extracts that presented the highest antitumor activity. These isolates were molecularly identified from sequencing of the spacer region of the ribosomal DNA internal transcript (ITS). A metabolite production curve was performed with selected isolates to determine the time of the highest antitumor activity. Results: Ten endophytic fungi from L. marginatus were isolated and morphologically characterized. Results showed that aqueous extracts presented lower lymphoma cells growth inhibition (\u3c 50%) at the highest concentration evaluated (250 µg/mL), as compared with ethyl acetate and methanolic extracts, which showed up to 93.4% and 94.3% cells growth inhibition, respectively. Ten extracts with \u3e 80% tumor cells growth inhibition were selected and evaluated at 250 µg/mL on PBMCs viability. Extracts showing less than 50% cytotoxicity to PBMCs were selected and IC50 and IS were determined. Strain PME-H005 presented the highest toxicity against L5178Y-R cells and the highest SI with IC50 of 39.7 µg/mL and IS \u3e 6.2, as compared with PBMCs. Four isolates that showed the highest antitumor activity were molecularly identified, corresponding to the species Penicillium citrinum, Aspergillus versicolor, Metarhizium anisopliae, and Cladosporium sp. When performing the metabolite production curve, it was observed that only A. versicolor PME-H005 and M. anisopliae PME-H007 strains retained antitumor activity, where the ethyl acetate extracts showed the highest activity with IC50 values of 23.2 µg/ mL (28 d) for the PME-H005 strain and 2.7 µg/mL (21 d) for PME-H007. Conclusions: A. versicolor PME-H005 and M. anisopliae PME-H007 strains extracts showed significant antitumor activity against L5178Y-R lymphoma cells. Further research is required to characterize bioactive compounds responsible for this activity

Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV)-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like <it>env </it>gene sequences.</p> <p>Results</p> <p>The MMTV-like <it>env </it>gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number <ext-link ext-link-id="AY161347" ext-link-type="gen">AY161347</ext-link>. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the <it>env </it>sequences exhibited disruption of the reading frame due to mutations.</p> <p>Conclusion</p> <p>In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18%) of the lung carcinomas and 1 out of 7 (14%) of acute inflamatory lung infiltrate specimens studied of a Mexican Population.</p

A novel formulation technology for baculoviruses protects biopesticide from degradation by ultraviolet radiation

Biopesticides are biological pest control agents that are viewed as safer alternatives to the synthetic chemicals that dominate the global insecticide market. A major constraint on the wider adoption of biopesticides is their susceptibility to the ultraviolet (UV: 290–400 nm) radiation in sunlight, which limits their persistence and efficacy. Here, we describe a novel formulation technology for biopesticides in which the active ingredient (baculovirus) is micro-encapsulated in an ENTOSTAT wax combined with a UV absorbant (titanium dioxide, TiO2). Importantly, this capsule protects the sensitive viral DNA from degrading in sunlight, but dissolves in the alkaline insect gut to release the virus, which then infects and kills the pest. We show, using simulated sunlight, in both laboratory bioassays and trials on cabbage and tomato plants, that this can extend the efficacy of the biopesticide well beyond the few hours of existing virus formulations, potentially increasing the spray interval and/or reducing the need for high application rates. The new formulation has a shelf-life at 30 °C of at least 6 months, which is comparable to standard commercial biopesticides and has no phytotoxic effect on the host plants. Taken together, these findings suggest that the new formulation technology could reduce the costs and increase the efficacy of baculovirus biopesticides, with the potential to make them commercially competitive alternatives to synthetic chemicals

ALTERATIONS OF ANTITUMOR AND METABOLIC RESPONSES IN L5178Y-R LYMPHOMA-BEARING MICE AFTER ONLY 30-MINUTE DAILY CHRONIC STRESS EXPOSURE

Aim: In stress research, reducing times of stress induction may contribute to improving the well-being of experimental animals, especially in cancer models, already under physiological distress. To support this idea, we evaluated the effects of a short-timed stress protocol on endocrine, metabolic and immune indicators in mice bearing the L5178Y-R lymphoma. Materials and Methods: A 30-minute daily stress protocol was applied for 28 days to healthy and lymphoma-bearing BALB/c mice; body weight, plasma levels of corticosterone, norepinephrine, Th1/Th2 cytokines, insulin, and leptin, were measured. Results: We found a 12% significant decrease in body weight in non-tumor bearing mice under stress (p < 0.007). The disruption of weight evolution was accompanied by a stress induced 85% decrease in plasmatic leptin (p < 0.01) and total reduction of insulin. Tumor burden alone was associated to an increase in more than two-fold of plasmatic levels of norepinephrine (p < 0.008). Neither stress nor tumor or their combination, resulted in an elevation of systemic IL-6. IFN-γ levels were 20 times higher in lymphoma-bearing animals when compared with non-tumor bearing mice (p < 0.01); however, under stress, this response was reduced by half, indicating a suppressing effect of chronic stress on the antitumor immune response. Conclusion: A short-timed stress induction is enough to cause significant alterations in the metabolism and immunity of healthy and tumor-bearing mice, supporting the use of short-timed protocols as an efficient way to induce chronic stress that also considers concerns regarding the well-being of experimental animals in biomedical research

Antimicrobial and Antiinflammatory Potential of the Swedish Herbs Extract

Oral conditions that produce the greatest damage on individuals are cavities and periodontal disease, hence non-expensive and effective solutions are immediately required, particularly for communities with no access to dental services. The antimicrobial and anti-inflammatory potential of the Swedish bitter herbal extract was evaluated, using pure microbial cultures and clinical samples of 29 patients. It was observed that the extract caused significant (p<0.05) in vitro growth inhibition of up to 29%, 17%, 15%, and 50% against Prevotella intermedia, Bacteroides forsythus, Porphyromonas gingivalis and Streptococcus intermedius, respectively. In addition, the extract significantly (p<0.05) inhibited oral flora growth in patient samples showing MICs of < 7.8 μg/ml in 21% of the patients, 15.6μg/ml in 17% of the patients, 31.2 μg/ml in 10% of the patients, 62.5 μg/ml in 17% of the patients, 125 μg/ml in 3% of the patients, and 250 μg/ml in 7% of the patients, and induced a maximum of 75% growth inhibition, as measured by the MTT reduction assay. The extract was also observed to significantly suppress production of the inflammatory marker nitric oxide by LPS-treated murine peritoneal macrophages. The Swedish herbal extract may be considered in the clinics to prevent or treat bacterial oral infections and at the same time reducing inflammation