Uncovering the neuroprotective effect of vitamin B12 in pneumococcal meningitis: insights into its pleiotropic mode of action at the transcriptional level.

Background: The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl. Material and methods: Eleven-day-old rats were infected with S. pneumoniae via intracisternal injection and then administered either vitamin B12 or a placebo. After 24 hours of infection, the animals were euthanized, and apoptosis in the hippocampal dentate gyrus, microglia activation, and the inflammatory infiltrate were quantified in one brain hemisphere. The other hemisphere was used for RNA-Seq and RT-qPCR analysis. Results: In this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug. Conclusion: B12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.

Antimicrobial photodynamic therapy for the treatment of oral mucositis-A comparative study.

OBJECTIVES: The aim was to evaluate the effectiveness of photobiomodulation and antimicrobial photodynamic therapy in the treatment of oral mucositis. BACKGROUND: Oral Mucositis is a frequent complication of oral cavity and oropharynx cancer. Considering the OM aggravation by microorganisms contamination, disinfection provide by antimicrobial photodynamic therapy could be an effective approach. MATERIAL AND METHODS: This comparative study included fourteen patients undergoing radiochemotherapy for oral cavity and oropharynx cancer treatment, who developed oral mucositis. CONTROL GROUP: photobiomodulation. Intervention group: photobiomodulation and antimicrobial photodynamic therapy. The lesion size, duration, pain, and identification of microorganisms were evaluated. RESULTS: The mean reduction in oral mucositis size in the intervention group was 0.70 cm² (±0.35) and 0.30 cm² (±1.10) for the control group. The mean duration of oral mucositis was 18.37 days (±12.12) for the intervention group and 23 days (±14.78) for the control group. The intervention group had a mean reduction of 3.40 points on the pain scale (±2.44), while the control group had 0.17 (±2.28). In the intervention group, the predominant isolated microbiota was featured as mixed culture (n = 4/ 50%), followed of Gram Positive (n = 3/ 37.50%), and Gram Negative (n = 1/ 12.55%). In the control group, mixed culture was also more frequent (n = 4 / 66%), followed by Gram Positive (n = 2 /34%). Gram Negative was not predominantly isolated in the control group. CONCLUSION: No statistical significance was found between PBM-T alone and PBM-T + PDT. However, the better outcomes reached by PBM-T + PDT group would suggest there could be a role for combined treatment in the management of OM lesions.

O papel dos receptores de fator de crescimento epidérmico EGFR e HER2 e da topoisomerase IIα no carcinoma peniano / The role of epidermal growth factor receptorsEGFR and HER2 and of topoisomerase IIα in penile cancer

Introdução: O carcinoma peniano (CP) é frequente em países em desenvolvimento e, na presença de metástases nos linfonodos, as opçõesterapêuticas são restritas. Os receptores de fator de crescimento epidérmicoHER1 (ou EGFR) e HER2 são superexpressos em muitas neoplasias e alvos para terapias. EGFR é amplamente expresso em CP e parece haver benefício clínico para pacientes com o uso de terapia anti-EGFR. A expressão de HER2, que atua em pares com EGFR, não é reportada em CP; mas dados anteriores de nosso grupo mostram associação com sobrevida reduzida. Marcadores de proliferação celular, como Ki-67, são controversos. Topoisomerase IIα (TOP2a) é um marcador proliferativo geralmente co-amplificado com HER2. O presente estudo objetivou avaliar: (a) expressão de formas mutadas de EGFR (mutação L858R, no éxon 21; e deleção E746-A750, no éxon 19) em 135 casos de CP emblocados em parafina, através de imuno-histoquímica (IHQ); (b) presença de mutações nos quatro éxons codificadores do domínio tirosina-cinase de EGFR (18, 19, 20 e 21) em 29 casos congelados através de sequenciamento; (c) alterações no número de cópias gênicas de EGFR, HER2 e TOP2a através de FISH em 70 casos; (d) expressão de topoisomerase IIα (TOP2a) nos 135 casos, através de IHQ e, por fim, (e) associar os achados com variáveis clínicas, patológicas e sobrevida. Resultados: Os casos de CP avaliados foram negativos para as mutações estudadas por IHQ (nos éxons 19 e 21) e por sequenciamento (éxons 18 a 21). Quanto à análise de EGFR por FISH, amaioria dos casos (79,3%) apresentou dissomia, 16 casos (23,5%) apresentaram polissomia do cromossomo 7 e seis casos (8,9%) ganhos de EGFR. Casos aumento do número de cópias de EGFR (ancEGFR), seja por polissomia ou ganhos do gene, se associaram a mais alto grau (p=0,014) e menor taxa de sobrevida global (p=0,046) e câncer-específica (p=0,005)...