Inflammation plays a critical role in the response to and survival from injuries and/or infections. It occurs in two phases: initiation and resolution; however, when these events do not resolve and persist over time, the inflammatory response becomes chronic, prompting diseases that affect several systems and organs, such as the vasculature and the skin. Here, we reviewed inflammation that occurs in selected infectious and sterile pathologies. Thus, the immune processes induced by bacterial sepsis as well as T. cruzi and SARS-CoV-2 infections are shown. In addition, vaccine adjuvants as well as atherosclerosis are revised as examples of sterile-mediated inflammation. An example of the consequences of a lack of inflammation resolution is given through the revision of wound healing and chronic wounds. Then, we revised the resolution of the latter through advanced therapies represented by cell therapy and tissue engineering approaches, showing how they contribute to control chronic inflammation and therefore wound healing. Finally, new pharmacological insights into the management of chronic inflammation addressing the resolution of inflammation based on pro-resolving mediators, such as lipoxin, maresin, and resolvins, examining their biosynthesis, biological properties, and pharmacokinetic and pharmaceuticals limitations, are given. We conclude that resolution pharmacology and advanced therapies are promising tools to restore the inflammation homeostasis.

The neglected Chagas disease, a zoonosis caused by the Trypanosoma cruzi parasite, has limited treatment options like nifurtimox and benznidazole, known for their toxic effects and controversial efficacy. Natural products present opportunities for therapeutic alternatives, particularly in Chile, which has a rich variety of endemic flora. This study focused on the Chilean Buddleja globosa, evaluating the antioxidant activities and biological effects of its methanolic extract (MET) and BG500, an enriched iridoid fraction (6-O-methylcatalpol), against T. cruzi trypomastigotes. Although the trypanocidal activity of the extract was significantly lower than that of nifurtimox (280 ± 3.5 vs. 5.0 ± 0.5), its selectivity was comparable (selectivity index > 15). The MET and enriched fraction also induced hyperpolarization of mitochondrial membrane potential (ΔΨm). In silico docking studies suggested that T. cruzi’s Old Yellow (OYE) could be a potential target for 6-O-methylcatalpol. This work provides the first report on the potential trypanocidal activity of a B. globosa extract, highlighting the need for further studies to connect ΔΨm and OYE inhibition to the effects of 6-O-methylcatalpol.

Periodontitis has been associated with adverse pregnancy outcomes, but the effect of oral pathogens on placental tissue and local immunity remains unclear. In this study, we investigated the response of human placental explants (HPEs) to lysates of Porphyromonas (P.) gingivalis, a keystone periodontal pathogen. Exposure to P. gingivalis induced significant histological damage and extracellular matrix degradation in placental tissue. The lysate activated the canonical NF-κB pathway, as demonstrated by increased phosphorylation of IκBα, particularly in the trophoblast. This activation was predominantly mediated by Toll-like receptor 2 (TLR-2), with partial contribution from TLR-4. Notably, TLR-2 protein levels decreased upon stimulation, while soluble (s) TLR-2 was markedly elevated in culture supernatants, suggesting receptor cleavage as a regulatory mechanism. P. gingivalis also triggered a robust proinflammatory cytokine secretion, including IL-1β, IL-6, IL-8, and TNF-α, with variable dependence on TLR-2 and TLR-4 signaling. These findings reveal that P. gingivalis components elicit a complex innate immune response in the placenta, driven by TLR-mediated NF-κB activation and modulated by sTLR-2. This study provides mechanistic insight into how periodontitis may contribute to placental inflammation and highlights potential pathways linking maternal oral health to pregnancy complications.