Viral manipulation of a mechanoresponsive signaling axis disassembles processing bodies

Processing bodies (PBs) are ribonucleoprotein granules important for cytokine mRNA decay that are targeted for disassembly by many viruses. Kaposi’s sarcoma-associated herpesvirus is the etiological agent of the inflammatory endothelial cancer, Kaposi’s sarcoma, and a PB-regulating virus. The virus encodes Kaposin B (KapB), which induces actin stress fibres (SFs) and cell spindling as well as PB disassembly. We now show that KapB-mediated PB disassembly requires actin rearrangements, RhoA effectors and the mechanoresponsive transcription activator, YAP. Moreover, ectopic expression of active YAP or exposure of ECs to mechanical forces caused PB disassembly in the absence of KapB. We propose that the viral protein KapB activates a mechanoresponsive signaling axis and links changes in cell shape and cytoskeletal structures to enhanced inflammatory molecule expression using PB disassembly. Our work implies that cytoskeletal changes in other pathologies may similarly impact the inflammatory environment.

α-bisabolol Exerts Anti-inflammatory Action and Ameliorates Collagen-induced Arthritis in Rats

Background: Development of synovial hypertrophy, articular tissue inflammation and tenderness in joints is the characteristic feature of rheumatoid arthritis. Drugs that are derived from natural sources which target inflammation with reduced side-effects receive much attention. Hence, the present study was designed to investigate the anti-arthritic effects of α-bisabolol, a natural chamomile essential oil and also an anti-inflammatory molecule on the rat model of collagen-induced arthritis (CIA). Methods: Animal model of CIA was established and orally administered with α-bisabolol (100 mg/kg) or vehicle and the pathological and inflammatory parameters were evaluated. Result: The results of the present findings indicate that α-bisabolol treatment ameliorates CIA-induced inflammation via inhibiting the proteases and inflammatory mediators suggesting that α-bisabolol may be a potential candidate against arthritis inflammations.

Syringol Isolated From Eleusine Coracana (L.) Gaertn Bran Suppresses Inflammatory Response Through the Down-Regulation of cPLA2, COX-2, IκBα, p38 and MPO Signaling in sPLA2 Induced Mice Paw Edema.

Eleusine coracana (L.) Gaertn (E. coracana) is one of the highest consuming food crops in Asia and Africa. E. coracana is a plant with several medicinal values including anti-ulcerative, anti-diabetic, anti-viral and anti-cancer properties. However, the anti-inflammatory property of E. coracana remains to be elucidated. Therefore, the objective of present study was to investigate the potential in isolated molecule from E. coracana via a combination of in vitro, in vivo and in silico methods. In this study we have isolated, purified and characterized an anti-inflammatory molecule from E coracana bran extract known as syringol. Purification of syringol was accomplished by combination of GC-MS and RP-HPLC techniques. Syringol significantly inhibited the enzyme activity of sPLA2 (IC50 = 3 µg) and 5-LOX (IC50 = 0.325 µg) in vitro. The inhibition is independent of substrate concentration, calcium ion concentration and was irreversible. Syringol interacts with purified sPLA2 enzymes as evidenced by fluorescence and molecular docking studies. Further, the syringol molecule dose dependently inhibited the development of sPLA2 and carrageenan induced edema. Furthermore, syringol decreases the expression of cPLA2, COX-2, IκBα, p38 and MPO in edematous tissues as demonstrated by western blots. These studies revealed that syringol isolated from E coracana bran may develop as a potent anti-inflammatory molecule.

What is new in Purinergic Signaling and Cervical Cancer?

Since our publication “Purinergic Signaling and Tumor Microenvironment in Cervical Cancer” [1], in early 2020, there has been a significant change in purinergic signaling research. The Coronavirus disease 2019 (COVID-19) significantly impacted the prevention, diagnosis, and treatment of cervical cancer [2]. In that previous review, we had addressed the possibilities of purinergic signaling in the tumor microenvironment of this type of cancer [1]. The conclusions were: the extracellular medium of cervical cancer is rich in adenosine triphosphate (ATP) and adenosine [3, 4, 5]; ATP is a pro-inflammatory molecule that has an affinity for P2X2, P2X4, and P2X7 receptors [6]; this activation leads to apoptosis of the cells of the cervix [7]; P2X7 is still involved in stimulating factors that lead to mitogenic and angiogenic pathways [8]; there is a variant of P2X7 in cervical cancer cells, P2X7j, which decreases permeability and cell death [9, 10, 11]. The P2Y1, P2Y2, and P2Y6 receptors, in turn, have the effect of tumor progression [12]. The review also contributed to the understanding of adenosine, which would activate A2A receptors on T lymphocytes, which would promote a decrease in the proliferation and effector function of such cells

Anti-Apoptotic and Anti-Inflammatory Role of Trans ε-Viniferin in a Neuron–Glia Co-Culture Cellular Model of Parkinson’s Disease

The polyphenol trans-ε-viniferin (viniferin) is a dimer of resveratrol, reported to hold antioxidant and anti-inflammatory properties. The aims of our study were to evaluate the neuroprotective potential of viniferin in the nerve growth factor (NGF)-differentiated PC12 cells, a dopaminergic cellular model of Parkinson’s disease (PD) and assess its anti-inflammatory properties in a N9 microglia–neuronal PC12 cell co-culture system. The neuronal cells were pre-treated with viniferin, resveratrol or their mixture before the administration of 6-hydroxydopamine (6-OHDA), recognized to induce parkinsonism in rats. Furthermore, N9 microglia cells, in a co-culture system with neuronal PC12, were pre-treated with viniferin, resveratrol or their mixture to investigate whether these polyphenols could reduce lipopolysaccharide (LPS)-induced inflammation. Our results show that viniferin as well as a mixture of viniferin and resveratrol protects neuronal dopaminergic cells from 6-OHDA-induced cytotoxicity and apoptosis. Furthermore, when viniferin, resveratrol or their mixture was used to pre-treat microglia cells in our co-culture system, they reduced neuronal cytotoxicity induced by glial activation. Altogether, our data highlight a novel role for viniferin as a neuroprotective and anti-inflammatory molecule in a dopaminergic cellular model, paving the way for nutraceutical therapeutic avenues in the complementary treatments of PD.

Inhibition of miRNA-155 Alleviates High Glucose-Induced Podocyte Inflammation by Targeting SIRT1 in Diabetic Mice

Objective. Microinflammation plays a crucial role in podocyte dysfunction in diabetic nephropathy, but its regulatory mechanism is still unclear. This study is aimed at discussing the mechanisms underlying the effect of miRNA-155 on podocyte injury to determine its potential as a therapeutic target. Methods. Cultured immortalized mouse podocytes and diabetic KK-Ay mice models were treated with a miR-155 inhibitor. Western blotting, real-time PCR, ELISA, immunofluorescence, and Luciferase reporter assay were used to analyze markers of inflammation cytokines and podocyte injury. Results. miRNA-155 was found to be highly expressed in serum and kidney tissue of mice with diabetic nephropathy and in cultured podocytes, accompanied by elevated levels of inflammatory factors. Inhibition of miRNA-155 can reduce proteinuria and ACR levels, diminish the secretion of inflammatory molecules, improve kidney function, inhibit podocyte foot fusion, and reverse renal pathological changes in diabetic nephropathy mice. Overexpression of miRNA-155 in vitro can increase inflammatory molecule production in podocytes and aggravates podocyte injury, while miRNA-155 inhibition suppresses inflammatory molecule production in podocytes and reduces podocyte injury. A luciferase assay confirmed that miRNA-155 could selectively bind to 3 ′ -UTR of SIRT1, resulting in decreased SIRT1 expression. In addition, SIRT1 siRNA could offset SIRT1 upregulation and enhance inflammatory factor secretion in podocytes, induced by the miRNA-155 inhibitor. Conclusions. These findings strongly support the hypothesis that miRNA-155 inhibits podocyte inflammation and reduces podocyte injury through SIRT1 silencing. miRNA-155 suppression therapy may be useful for the management of diabetic nephropathy.

Recent Advances in Molecular Hydrogen Research Reducing Exercise-Induced Oxidative Stress and Inflammation

: Physical exercise-induced oxidative stress and inflammation may be beneficial when exercise is a regular activity, but it is rather harmful when exercise is exhaustive and performed by unaccustomed organisms. Molecular hydrogen (H2 ) has recently appeared as a potent antioxidant and anti-inflammatory molecule in numerous pathological conditions. However, its role is relatively unknown under physiological conditions such as physical exercise. Therefore, this review summarizes the current knowledge of the H2 reducing oxidative stress and inflammation in physical exercise, reporting data from both animal and human studies.