Effect of Lonomia obliqua Venom on Human Neutrophils

The significant incidence of deforestation in South America culminates in the contact of humans with typical forests species. Among these species, one may highlight Lonomia obliqua caterpillar, which, when touched by humans, can poison them through their bristles. Therefore, better acknowledging the mechanisms involved in envenomation caused by Lonomia obliqua caterpillar bristle extract (LOCBE) may contribute to further treatments. Recently, we demonstrated that LOCBE induces a pro-inflammatory profile in endothelial cells; thus, we decided to investigate the effects of LOCBE on human polymorphonuclear neutrophils (PMN), which are the first leukocytes that migrate to the inflammatory focus. Our results showed that treatment with LOCBE induced PMN chemotaxis together with alterations in actin cytoskeleton and focal adhesion kinase (FAK) activation, favoring migration. Concurrently, LOCBE induced PMN adhesion to matrix proteins, such as collagen IV, fibronectin, and fibrinogen. Moreover, we observed that LOCBE attenuated PMN apoptosis and increased reactive oxygen species (ROS) production together with nuclear factor kB (NF-κB) activation—a redox-sensitive transcription factor—as well as interleukin (IL)-1β and IL-8 release. We call attention to the ROS-dependent effect of LOCBE on increased cell migration once an antioxidant treatment reverted it. In summary, we report that LOCBE activates PMN, inducing pro-inflammatory responses modulated by ROS.

A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19

Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases.

Study of growth characteristics of callus, suspension and root crops Scutellaria baicalensis

Scutellaria baicalensis is a popular traditional plant in Chinese medicine. Widely distributed biologically active substances of Scutellaria baicalensis are flavonoids (baicalin, baicalein, vogonin and vogonoside), which are responsible for the antitumor activity. Their antitumor effect is due to the absorption of oxidative radicals, the weakening of the activity of NF-kB (nuclear factor-kB), the suppression of the expression of the COX-2 gene and the regulation of the cell cycle. In addition, baicalein, baicalin, and vogonin showed strong antioxidant activity. The root culture in vitro of the medicinal plant Scutellaria baicalensis is characterized by intensive growth. The growth index at the end of the cultivation cycle was 40. The growth curve has a standard S-shape, with pronounced growth phases. The stationary phase was observed from 5-7 weeks of cultivation. The root culture growth index was 22.

Homozygous NF-kB1 mutation causing combined immunodeficiency: a histopathological analysis

Introduction: The nuclear factor-kB (NF-kB) signaling pathway plays a major role in mediating multiple cellular processes, including immune and inflammatory responses. Aims: We describe the histopathological findings of lymph nodes from a patient with a homozygous NF-kB subunit 1 (NF-kB1) mutation causing a combined immunodeficiency phenotype. Results: A nodal biopsy was performed for lymphadenopathy evaluation, in the context of development of persistent EBV infection. Our findings show that this patient has normal lymph node tissue present, however, abnormal histopathology features were observed, including atrophic germinal centers. B cell subset components within the B cell domain were also analyzed. The development of the B cell response during EBV infection was found to be significantly impaired. Conclusion: Aberrant signaling due to NF-kB1 deficiency has a significant impact on the development of B cell immunoproliferative responses. Statement of novelty We report on the abnormal histopathology findings of lymph node biopsy from a patient with homozygous NF-kB1 mutation.

Medicinal benefits and scientific justification of Commiphora mukul (Muqil): A review

Commiphora mukul (Muqil or Guggul), oleo-gum, has been in use for thousands of years as a medicine in Unani and Ayurvedic medicinal systems. It was primarily used for swellings, inflammation, piles, arthritis and urinary disorders. Among its various types Muqil-I-Arzaq, a gum, having reddish hue is considered to be the best form of Muqil for medicinal purposes. It has been revealed to inhibit the nuclear factor-kb, a regulator of inflammatory response, and act as a potent antagonist to the receptors of androgens, mineralocorticoides, and glucocorticoides. Muqil is a versatile herb with diverse medicinal benefits which demand scientific validation. A coherent review of properties, medicinal benefits, traditional uses and scientific studies of Muqil, along with the overall processes involved from collection to consumption is judiciously described in this paper. The aim of this review is to provide a base for multiple research works, validating Commiphora mukul in different chronic ailments. keywords: Commiphora mukul, Inflammation, Muqil, Nuclear factor-KB, Unani

EZH2 Promotes Extracellular Matrix Degradation via Nuclear Factor-kB(NF-kB)and p38 signaling Pathways in Pulpitis.

Background: Pulpitis is a complicated chronic inflammatory process which in a dynamic balance between damage and repair. Extracellular matrix plays an important regulatory role in wound healing and tissue repair. The aim of this study was to explore role of the epigenetic mark, enhancer of zeste homolog 2 (EZH2) on the degradation of extracellular matrix during pulpitis. Methods : Quantitative polymerase chain reaction was used to assess the expression of matrix metalloproteinases (MMPs) and type I collagen in HDPCs upon EZH2 and EI1 stimulation. The mechanism of EZH2 affecting extracellular matrix was explored through quantitative polymerase chain reaction and Western blot. A rat model of dental pulp inflammation was established, and the expression of type I collagen in dental pulp under EZH2 stimulation was detected by immunohistochemical staining. Results :EZH2 upregulated the expression of MMP-1, MMP-3, MMP-8 and MMP-10 and decreased the production of type I collagen in HDPCs, while EI1 had the opposite effect .EZH2 activated the Nuclear Factor-kB(NF-kB)and p38 signaling Pathways in HDPCs, the inhibition of which reversed the induction of MMPs and the suppression of type I collagen .EZH2 can downregulated the type I collagen levels in an experimental model of dental pulpitis in rats. Conclusion: EZH2 promotes extracellular matrix degradation via Nuclear Factor-kB(NF-kB)and P38 signaling pathways in pulpitis.EZH2 can decrease the type I collagen levels in vivo and vitro.