BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility.

Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, a transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. We found that BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion in Mtb-infected mice increased glutathione levels and Gpx4 expression that inhibit lipid peroxidation. Bach1-/- macrophages exhibited increased resistance to Mtb-induced cell death, while Mtb-infected Bach1-deficient mice displayed reduced bacterial loads, pulmonary necrosis and lipid peroxidation concurrent with increased survival. Single-cell RNA-seq analysis of lungs from Mtb-infected Bach1-/- mice revealed an enrichment of genes associated with ferroptosis suppression. Bach1 depletion in Mtb-infected B6.Sst1S mice that display human-like necrotic lung pathology also markedly reduced necrosis and increased host resistance. These findings identify Bach1 as a key regulator of cellular and tissue necrosis and host resistance in Mtb infection.

Influence of laser therapy on the dynamic formation of extracellular matrix in standard second degree burns treated with bacterial cellulose membrane.

The present study aims to assess the influence of Aluminum-Gallium-Indium-Phosphide laser (AlGaInP laser, λ = 660 nm), whether or not in association with the application of a membrane of bacterial cellulose (Nexfill™), during recovery from induced second-degree burns at the dorsum of Wistar rats. (Rattus norvegicus, Wistar). Forty-eight animals have been distributed into four groups: Control (burns remained untreated), Group I (laser-treated), Group II (treated with Nexfill), and Group III (laser + Nexfill™). In addition to a morphological analysis, immunohistochemical analysis has been performed for type I collagen, type III collagen, fibronectin, and laminin. The Fisher's Test was used to assess differences among groups (p < 0,05). A larger amount of collagen type III was observed in Control, Group II and Group III when compared with Group I (p < 0,05). Group I and Group III have shown a greater collagen deposition when compared with Group II (p < 0,05), but the amount of collagen was similar in Group I, Group III, and Control. Group III has shown larger fibronectin amounts in comparison with Group II (p < 0,05). As regards laminin, Group I has shown a predominant discontinuity pattern on the basal lamina in comparison with Control, Group II, and Group III (p < 0,05). It is concluded that in this current study the laser when used alone (Group I) hasn't influenced collagen deposition neither has it acted on fiber pattern (fibril and/or reticular). Moreover, laser application hasn't accelerated the repair of wounds caused by inflicted second-degree burns.