Inflammation driven by intracellular activation of the NLRP3 inflammasome is involved in the pathogenesis of a variety of diseases including vascular pathologies. Inflammasome specks are released into the extracellular compartment from disrupting pyroptotic cells. The potential uptake and function of extracellular NLRP3 inflammasomes in human coronary artery smooth muscle cells (HCASMC) are unknown. Fluorescently labeled NLRP3 inflammasome particles were isolated from a mutant NLRP3-YFP cell line and used to treat primary HCASMC for 4 and 24 h. Fluorescent and expressional analyses showed that extracellular NLRP3-YFP particles are internalized into HCASMC, where they remain active and stimulate intracellular caspase-1 (1.9-fold) and IL-1β (1.5-fold) activation without inducing pyroptotic cell death. Transcriptomic analysis revealed increased expression level of pro-inflammatory adhesion molecules (ICAM1, CADM1), NLRP3 and genes involved in cytoskleleton organization. The NLRP3-YFP particle-induced gene expression was not dependent on NLRP3 and caspase-1 activation. Instead, the effects were partly abrogated by blocking NFκB activation. Genes, upregulated by extracellular NLRP3 were validated in human carotid artery atheromatous plaques. Extracellular NLRP3-YFP inflammasome particles promoted the secretion of pro-atherogenic and inflammatory cytokines such as CCL2/MCP1, CXCL1 and IL-17E, and increased HCASMC migration (1.8-fold) and extracellular matrix production, such as fibronectin (5.8-fold) which was dependent on NFκB and NLRP3 activation. Extracellular NLRP3 inflammasome particles are internalized into human coronary artery smooth muscle cells where they induce pro-inflammatory and pro-atherogenic effects representing a novel mechanism of cell-cell communication and perpetuation of inflammation in atherosclerosis. Therefore, extracellular NLRP3 inflammasomes may be useful to improve the diagnosis of inflammatory diseases and the development of novel anti-inflammatory therapeutic strategies.

The use of synthetic drugs has increased in recent years; however, herbal medicine is yet more trusted among a huge population worldwide; This could be due to minimal side effects, affordable prices, and traditional beliefs. Lemongrass ( Melissa officinalis) has been widely used for reducing stress and anxiety, increasing appetite and sleep, reducing pain, healing wounds, and treating poisonous insect bites and bee stings for a long time. Today, research has shown that this plant can also fight viruses including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Herpes Simplex Virus (HSV), and Human Immunodeficiency Virus (HIV) through various mechanisms such as inhibiting HSV-1 from binding to host cell, inhibiting HSV-1 replication during the post-adsorption or inhibiting main protease and spike protein of SARS-CoV-2, furthermore, be effective in treating related diseases. This Review investigated the antiviral properties of Melissa officinalis and its effect on viral diseases. More in vitro and in vivo studies are needed to determine Melissa officinaliss underlying mechanism, and more randomized controlled trials should be done to identify its effect in humans. Also, due to the usefulness and lack of side effects, it can be used more as a complementary medicine.

Modern tissue engineering has made substantial advancements that have revolutionized plastic surgery. Acellular dermal matrix (ADM) is an example that has gained considerable attention recently. ADM can be made from humans, bovines, or porcine tissues. ADM acts as a scaffold that incorporates into the recipient tissue. It is gradually infiltrated by fibroblasts and vascularized. Fortunately, many techniques have been used to remove cellular and antigenic components from ADM to minimize immune system rejection. ADM is made of collagen, fibronectin, elastin, laminin, glycosaminoglycans, and hyaluronic acid. It is used in critical wounds (e.g., diabetic wounds) to protect soft tissue and accelerate wound healing. It is also used in implant-based breast reconstruction surgery to improve aesthetic outcomes and reduce capsule contracture risk. ADM has also gained attention in abdominal and chest wall defects. Some studies have shown that ADM is associated with less erosion and infection in abdominal hernias than synthetic meshes. However, its higher cost prevents it from being commonly used in hernia repair. Also, using ADM in tendon repair (e.g., Achilles tendon) has been associated with increased stability and reduced rejection rate. Despite its advantages, ADM might result in complications such as hematoma, seroma, necrosis, and infection. Moreover, ADM is expensive, making it an unsuitable option for many patients. Finally, the literature on ADM is insufficient, and more research on the results of ADM usage in surgeries is needed. This article aims to review the literature regarding the application, Benefits, and costs of ADM in reconstructive surgery.

Background and aims As part of the innate immune response, NLRP3 inflammasomes are involved in the process of sterile inflammation, IL-1β release and are key mediators of inflammation-related vascular diseases, such as atherosclerosis. Recent data showed the existence of extracellular inflammasomes released from monocytes during pyroptotic cell death. Their biological function in the vascular system is still not known. Here, we established a method to detect extracellular inflammasomes and tested the hypothesis that extracellular NLRP3 inflammasomes can be internalized by vascular cells, such as macrophages, endothelial cells and coronary smooth muscle cells and induce pro-inflammatory signaling. Methods and result Stimulation of THP1 monocytes and of isolated primary human monocytes with Lipopolysaccharide and Nigericin activated the NLRP3 inflammasome and induced pyroptosis and the release of inflammasome complexes. Extracellular inflammasomes were isolated from cell-free supernatant and identified as inflammasome complexes (oligomers) by immunoblot. For functional characterization, isolated fluorescent-labeled NLRP3 inflammasome complexes were shown to be internalized by THP1 macrophages (19.7±9.7% pos. cells), primary endothelial cells (HUVEC: 9.0±2.3% pos. cells, coronary artery endothelial cells: 11.0% ± 2.3% pos. cells) and coronary smooth muscle cells (42.8±9.9% pos.cells) using immunofluorescence staining, Z-stacks and imaging flow cytometric analysis. Extracellular NLRP3 inflammasomes (eNLRP3) induced pro-inflammatory signaling in macrophages by increasing IL1b and Tnfa gene expression (3.0- fold) as well as IL-1β release (con: 1.9 pg/ml vs. eNLRP3: 191.0 pg/ml). In coronary smooth muscle cells, treatment with extracellular inflammasomes increased endogenous Nlrp3 and IL1b gene expression as well as upregulation of Cell adhesion molecule 1 (Cadm1). Coronary artery endothelial cells showed also increased protein level of surface adhesion marker Intercellular Adhesion Molecule 1 (ICAM1). Conclusion Upon canonical NLRP3 inflammasome activation, mononuclear cells release inflammasome complexes into the extracellular space. Macrophages, endothelial cells and smooth muscle cells are able to internalize these extracellular inflammasome complexes that exert pro-inflammatory effects. These findings support the concept that cell-free NLRP3 inflammasomes act as extracellular signal molecules triggering pro-atherogenic signaling mechanisms in vascular cells. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Leipzig University, Medical Faculty