INFLUENCE OF PEPTIDE P34 ON GENE EXPRESSION OF LISTERIA MONOCYTOGENES AND LISTERIA SEELEGERI

Objective: Investigate the influence of the antimicrobial peptides P34 and nisin on the expression of genes associated with components of the cell surface of Listeria monocytogenes and Listeria seeligeri.Methods: Antimicrobial activity was determined by addition of peptide P34 and nisin (12.5 µg/ml) onto Brain Heart Infusion agar (BHI) plates previously inoculated with indicator strains (L. monocytogenes ATCC 7644 or L. seeligeri AC 82/4) after incubation for 24 h at 37 °C or 240 h at 4 °C. Ribonucleic acid (RNA) was directly extracted from bacterial colonies at the border of the inhibition zones, and the expression levels of genes D-alanine-D-alanyl carrier protein ligase (dltA), putative phospholipid lysinylation (Imo 1695) and EIIABMan of mannose-specific PTS (mptA) were determined using real-time PCR.Results: A non-significant increase in the levels of transcription of genes dltA, Imo1695 and mptA was observed for L. monocytogenes treated with peptide P34 or nisin. Both peptides caused a similar decrease in dltA gene expression in L. seeligeri. The expression of gene Imo1695 significantly decreased (about 2000-fold) after treatment with the peptide P34 at 37 °C, while at 4 °C a reduction of 12-fold and 5-fold was detected for P34 and nisin, respectively. A significant decrease in mptA gene expression was observed by exposition to peptide P34 (31.872-fold) and nisin (16.047-fold) for 24 h at 37 °C.Conclusion: The results suggest that both peptide P34 and nisin influence the expression of genes related with the cell-surface/cell-membrane structure of L. seeligeri and in lesser extent L. monocytogenes

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Amyloid-β peptide absence in short term effects on kinase activity of energy metabolism in mice hippocampus and cerebral cortex

ABSTRACT Considering that Alzheimer's disease is a prevalent neurodegenerative disease worldwide, we investigated the activities of three key kinases: creatine kinase, pyruvate kinase and adenylate kinase in the hippocampus and cerebral cortex in Alzheimer's disease model. Male adult Swiss mice received amyloid-β or saline. One day after, mice were treated with blank nanocapsules (17 ml/kg) or meloxicam-loaded nanocapsules (5 mg/kg) or free meloxicam (5 mg/kg). Treatments were performed on alternating days, until the end of the experimental protocol. In the fourteenth day, kinases activities were performed. Amyloid-β did not change the kinases activity in the hippocampus and cerebral cortex of mice. However, free meloxicam decrease the creatine kinase activity in mitochondrial-rich fraction in the group induced by amyloid-β, but for the cytosolic fraction, it has raised in the activity of pyruvate kinase activity in cerebral cortex. Further, meloxicam-loaded nanocapsules administration reduced adenylate kinase activity in the hippocampus of mice injected by amyloid-β. In conclusion we observed absence in short-term effects in kinases activities of energy metabolism in mice hippocampus and cerebral cortex using amyloid-β peptide model. These findings established the foundation to further study the kinases in phosphoryltransfer network changes observed in the brains of patients post-mortem with Alzheimer's disease

7-Chloro-4-(phenylselanyl) quinoline reduces renal oxidative stress induced by oxaliplatin in mice

Purpose: evaluating the relationship between oxidative damage oxaliplatin (OXA)-induced and the therapeutic potential of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) in kidney of mice. Methods: Mice received OXA (10 mg/kg) or vehicle by intraperitoneal route (days 0 and 2). Oral administration of 4-PSQ (1 mg/kg) or vehicle was performed on days 2 to 14. On day 15, the animals were euthanized, and the kidneys and blood collected. The effect of OXA and/or 4-PSQ on urea, thiobarbituric acid reactive species (TBARS), non-protein thiol (NPSH) and protein carbonyl (PC) levels were investigated. Moreover, renal superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), δ-aminolevulinic acid dehydratase (δ-ALA-D) and Na+, K+ ATPase activities were evaluated. Results: Our findings revealed an increase on urea levels and a significant renal oxidative damage in OXA-induced mice. OXA exposure increased SOD, GPx and GST activities and caused a reduction on NPSH levels, CAT and GR activities. Na+, K+ ATPase and -ALA-D activities were reduced by OXA. 4-PSQ decreased plasmatic urea levels and renal oxidative damage. SOD, GPx, CAT, GR and Na+, K+ ATPase activities were restored by 4-PSQ. Conclusion: 4-PSQ may be a good prototype for the treatment of OXA-induced renal injury.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

The Antinociceptive Responses of MTDZ to Paclitaxel−Induced Peripheral Neuropathy and Acute Nociception in Mice: Behavioral, Pharmacological, and Biochemical Approaches

The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclitaxel (PTX)-induced peripheral neuropathy was investigated in male and female Swiss mice. The study examined the effects of MTDZ on various pathways, including transient receptor potential cation channel subfamily V member 1 (TRPV1), glutamatergic, nitrergic, guanylate cyclase (cGMP), serotonergic, and opioidergic. Mice received intraperitoneal PTX (2 mg/kg) or vehicle on days 1, 2, and 3, followed by oral MTDZ (1 mg/kg) or vehicle from days 3 to 14. Mechanical and thermal sensitivities were assessed using Von Frey and hot plate tests on days 8, 11, and 14. The open field test evaluated locomotion and exploration on day 12. On day 15, nitrite and nitrate (NOx) levels and Ca2+−ATPase activity in the cerebral cortex and spinal cord were measured after euthanizing the animals. MTDZ administration reversed the heightened mechanical and thermal sensitivities induced by PTX in male and female mice without affecting locomotion or exploration. MTDZ also modulated multiple pathways, including glutamatergic, NO/L−arginine/cGMP, serotonergic (5−HT1A/1B), opioid, and TRPV1 pathways. Additionally, MTDZ reduced NOx levels and modulated Ca2+−ATPase activity. In conclusion, MTDZ effectively alleviated PTX−induced peripheral neuropathy and demonstrated multi-targeted modulation of pain-related pathways. Its ability to modulate multiple pathways, reduce NOx levels, and modulate Ca2+−ATPase activity makes it a potential pharmacological candidate for peripheral neuropathy, acute nociceptive, and inflammatory conditions. Further research is needed to explore its therapeutic potential in these areas

Therapeutic potential of selanyl amide derivatives in the in vitro anticholinesterase activity and in in vivo anti-amnesic action

The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two new selanyl amide derivatives in cerebral structures of mice. Our results demonstrated that N-(2-(3-(phenylselanyl)propoxy)phenyl)furan-2-carboxamide (1) and N-(2-(3-(phenylselanyl)propoxy)phenyl)thiophene-2-carboxamide (2) inhibited the in vitro AChE activity in mice. Another objective was assessed the effect of the best AChE inhibitor in an amnesic model induced by scopolamine (SCO) in male Swiss mice. The involvement of AChE activity and lipid peroxidation in the cerebral structures was investigated. Our results showed that compound 1 attenuated the latency to find the escape box and the number of holes visited in Barnes maze task, without altering the locomotor and exploratory activities in open-field test. Compound 1 protected against increasing in lipid peroxidation levels and AChE activity caused by SCO in the cerebral cortex and hippocampus of mice. In conclusion, the present study evidenced the in vitro anticholinesterase effect of two new selanyl amide derivatives in cerebral structures of mice. Moreover, compound 1, a selanyl amide derivative containing a furan ring, demonstrated anti-amnesic action due to its antioxidant and anticholinesterase activities in cerebral structures.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author