Lack of specific and efficient therapy leads to the high mortality rate of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Losartan is a potent pharmaceutical drug for ALI/ARDS. However, the protective effects and mechanisms of losartan remain incompletely known. This study evaluates the effects of losartan on ALI/ARDS and further investigates the possible mechanisms of these protective effects. Mice received i.p. injections of the AT1 inhibitor losartan (15 mg/kg), or control vehicle, half hour after cecal ligation and puncture (CLP). Plasma TNF-alpha, IL-1beta, and IL-6 cytokines were assayed 6 h after CLP. Blood gas, wet/dry lung weight ratio, lung tissue histology for occurrence of ALI/ARDS, and survival were examined. Lastly, nuclear factor kappaB (NF-kappaB) activations, IkappaB-alpha degradations, phosphorylations of p38 MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase expressions were evaluated in lung tissue. Losartan treatment significantly attenuated TNF-alpha, IL-6, and IL-1beta 6 h after CLP. Furthermore, losartan prevented blood gas and histopathologic appearance of ALI/ARDS after sepsis and significantly improved survival. Finally, losartan given after sepsis led to inhibition of lung tissue NF-kappaB activation (P < 0.01 vs. CLP group), attenuated degradation of IkappaB-alpha, and inhibited phosphorylation of p38MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase, pathways critical for cytokine release. These data reveal that losartan exerts a protective effect on ALI/ARDS, and this protective effect may be dependent, at least in part, on NF-kappaB and MAPK mechanisms.

Acute lung injury (ALI) is a frequent and serious complication of sepsis with limited therapeutic options. Gaining insights into the inflammatory dysregulation that causes sepsis‐associated ALI can help develop new therapeutic strategies. Herein, the crucial role of cell‐free mitochondrial DNA (cf‐mtDNA) in the regulation of alveolar macrophage activation during sepsis‐associated ALI is identified. Most importantly, a biocompatible hybrid protein nanomotor (NM) composed of recombinant deoxyribonuclease I (DNase‐I) and human serum albumin (HSA) via glutaraldehyde‐mediated crosslinking is prepared to obtain an inhalable nanotherapeutic platform targeting pulmonary cf‐mtDNA clearance. The synthesized DNase‐I/HSA NMs are endowed with self‐propulsive capability and demonstrate superior performances in stability, DNA hydrolysis, and biosafety. Pulmonary delivery of DNase‐I/HSA NMs effectively eliminates cf‐mtDNAs in the lungs, and also improves sepsis survival by attenuating pulmonary inflammation and lung injury. Therefore, pulmonary cf‐mtDNA clearance strategy using DNase‐I/HSA NMs is considered to be an attractive approach for sepsis‐associated ALI.

Immense progress in synthetic micro-/nanorobots with diverse functionalities has been made for biomedical applications during the last decade. However, there is still a huge gap for miniature robots to realize efficient therapy from in vitro to in vivo level. Here click chemistry is used to introduce curcumin-loaded hybrid cell membrane nanoparticles to magnetotactic bacteria AMB-1 with magnetic actuation, thus creating biohybrid microrobots CurNPs@2TM-AMB-1 for active and efficient pneumonia therapy in vivo. In the presence of an external rotating magnetic field, the developed AR are capable of moving controllably and wirelessly, and efficiently scavenging inflammatory factors and SARS-CoV-2 pseudovirus due to the existing receptors from the cell membrane cloaking strategy, thereby inhibiting the virus invasion and reducing the damage of inflammation to the lungs. Due to the active movement, AR significantly increase and prolong the accumulation of Cur in the lungs in vivo, thus alleviating the pneumonia and regulating pneumonia microenvironment. The designed hybrid microrobot system, with magnetic actuation and active neutralization of inflammatory factors and virus, shows great promise as a potential platform for pneumonia therapy.

Cell morphological analysis of SARS-CoV-2 infection by transmission electron microscopy