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- dactinomycin / Generic mfg., azithromycin / Generic mfg., macrocyclic peptide / UCB, Merck (MSD)
Rhesus theta defensin-1: an antimicrobial peptide with immunomodulatory properties for the treatment of cystic fibrosis. (HALL F) - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_3797;
Background: Rhesus Theta Defensin-1 (RTD-1) is a macrocyclic peptide isolated from Rhesus macaque leukocytes with dual anti-microbial and anti-inflammatory properties...Gene transcript stability was assessed using Actinomycin-D...THP-1 cytokine data for IL-1β and TNFα reveal RTD-1 more potently inhibits their production by 2-fold and 4-fold respectively when compared to Azithromycin, a commonly prescribed macrolide for treatment of airway inflammation in CF patients. These data demonstrate the anti-inflammatory mechanism of action of RTD-1 is partially mediated in part by inhibition of inflammasome activity.
- Cubicin (daptomycin) / Merck (MSD)
Daptomycin exerts a differential immunomodulatory effect on human monocytes exposed to mature biofilms of Staphylococcus aureus () - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_804;
DAP alone induces an immune cell recruitment and inflammatory response profile; however, MRSA BF does not allow this activation to occur. This suppressive response may constitute a decoy mechanism for the protection MRSA within a BF with potential serious complications to the patient’s health.
- | Kolchin (colchicine) / Incepta
Clinical, Journal: State of care for patients with systemic autoinflammatory diseases - Results of a tertiary care survey. (Pubmed Central) - Apr 4, 2019
...The diagnostic work-up included inflammatory markers and genetic testing, the first line treatment interleukin-1 (IL-1) blockers for CAPS and colchicine for FMF...The overall state of care for SAID patients was rated to be excellent or good by only 12% of departments, and to be poor or non-sufficient by 40% of departments. This study demonstrates a high need to improve the state of care and to harmonize diagnostic and treatment strategies for SAID patients.
- | Journal: Weighted Gene Co-expression Network Analysis for RNA-Sequencing Data of the Varicose Veins Transcriptome. (Pubmed Central) - Apr 4, 2019
Skeletal myofibril assembly pathway may play a crucial role in the pathogenesis of varicose veins. Characterization of these RNAs may provide new targets for understanding varicose veins diagnosis, progression, and treatment.
- | Journal: [Corrigendum] NLRP3 inflammasome is responsible for Hantavirus inducing interleukin‑1β in THP‑1 cells. (Pubmed Central) - Apr 4, 2019
The authors regret that this Figure was not corrected prior to the publication of this article, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 35: 1633‑1640, 2015; DOI: 10.3892/ijmm.2015.2162].
- | Review, Journal: Recent advances in inflammasome biology. (Pubmed Central) - Apr 3, 2019
Activation of this complex often involves the adaptor protein ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. Here we discuss new regulatory mechanisms that have been identified for the canonical inflammasomes, the most recently identified NLRP9b inflammasome, and the new gasdermin family of proteins that mediate pyroptosis and other forms of regulated cell death.
- | Preclinical, Journal, IO Biomarker: Anti-inflammatory effect of cinnamaldehyde and linalool from the leaf essential oil of Cinnamomum osmophloeum Kanehira in endotoxin-induced mice. (Pubmed Central) - Apr 3, 2019
In addition, cinnamaldehyde and linalool at the dose equivalent to their corresponding content in the tested dose of the leaf essential oil, which was 0.9Â mg/kg and 5.2Â mg/kg, respectively, showed similar or slightly less inhibitory activity for most of these inflammatory parameters compared with that of the leaf essential oil. Our data confirmed the potential use of leaf essential oil of Cinnamomum osmophloeum Kanehira as an anti-inflammatory natural product and provide evidence for cinnamaldehyde and linalool as two potent agents for prophylactic use in health problems associated with inflammations that being attributed to over-activated TLR4 and/or NLRP3 signaling pathways.
- | Review, Journal: Ion homeostasis and ion channels in NLRP3 inflammasome activation and regulation. (Pubmed Central) - Apr 3, 2019
Here, we discuss how the complex interplay of ion fluxes contributes to canonical, non-canonical, and alternative NLRP3 activation pathways that induce IL-1β secretion from immune cells. Particular attention is given to the concrete evidence for the involvement of ion channels, which may present viable therapeutic targets for the modulation of NLRP3 inflammasome activation.
- | Preclinical, Journal, PD(L)-1 Biomarker, IO Biomarker: Immunological behavior analysis of muscle cells under IFN-γ stimulation in vitro and in vivo. (Pubmed Central) - Apr 3, 2019
In Cardiotoxin-damaged tibialis anterior (TA) muscle, some regenerated myofibers expressed both MHC class I and class II molecules under IFN-γ enhanced inflammatory condition. Thus, our work demonstrates that muscle cells are active participants of local immune reactions.
- | Journal: Tetramethylpyrazine ameliorates experimental autoimmune encephalomyelitis by modulating the inflammatory response. (Pubmed Central) - Apr 3, 2019
Therefore, our results demonstrate that TMP (30 mg/kg) improved functional recovery in part by reducing inflammation in EAE mice. TMP may be a potential therapeutic agent for MS therapy.
- | Journal: Withaferin A attenuates ovalbumin induced airway inflammation. (Pubmed Central) - Apr 3, 2019
Notably, WA significantly reduced the activation of the NLRP3 inflammasome. The results indicate that WA may be an effective novel candidate for the treatment of airway inflammation.
- | Journal: Calcitriol inhibits ROS-NLRP3-IL-1β signaling axis via activation of Nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells. (Pubmed Central) - Apr 3, 2019
The results indicate that WA may be an effective novel candidate for the treatment of airway inflammation. The current study indicated that calcitriol could inhibit the priming stage of HS-induced cellular inflammation, highlighting its potential capacity to prevent and mitigate dry eye related corneal inflammation at an earlier stage.
- | probenecid / generics
Journal: Inflammasome Activation Induces Pyroptosis in the Retina Exposed to Ocular Hypertension Injury. (Pubmed Central) - Apr 2, 2019
...The OHT-induced release of cytokines and RGC death were significantly decreased in the retinas of Casp1Casp4(11), Panx1 and in Wild-type (WT) mice treated with the Panx1 inhibitor probenecid...Furthermore, they indicate an active contribution of neuronal NLRP1/NLRP3 inflammasomes and the pro-pyroptotic gasdermin D pathway to pathophysiology of the OHT injury. These results support the feasibility of inflammasome modulation for neuroprotection in OHT-injured retinas.
- |||| An exciting research pathway #NLRP3 #inflammasome #Alzheimers #DiabetesType3 #VascularDementia #fibrinogen #BloodBrainBarrier #Remnants #TRLs @Novartis @Amarincorp @skathire @DLBHATTMD (Twitter) - Apr 1, 2019
- | Brilliant talk by M. Heneka on Tau mediated NLRP3 modulation and insights on age-related transcriptomics of senescence markers! @adpdnet (Twitter) - Mar 31, 2019
- | Journal: Mutational profile of rare variants in inflammasome-related genes in Behçet disease: A Next Generation Sequencing approach. (Pubmed Central) - Mar 30, 2019
The maxima contribution corresponds to NOD2. This study supports influence of rare variants in genes involved in AIDs in the pathogenesis of BD.
- | Journal: Long noncoding RNA SNHG1 promotes neuroinflammation in Parkinson's disease via regulating miR-7/NLRP3 pathway. (Pubmed Central) - Mar 30, 2019
Downregulation of Snhg1 elevated miR-7 expression, suppressed the activation of microglia and NLRP3 inflammasome as well as dopaminergic neuron loss in the midbrain substantia nigra pars compacta in MPTP-treated mice. In conclusion, our study suggests that SNHG1 promotes neuroinflammation in the pathogenesis of PD via modulating miR-7/NLRP3 pathway.
- | Journal: Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis. (Pubmed Central) - Mar 30, 2019
Moreover, DCA significantly reduced the level of secretory immunoglobulin A (sIgA), and promoted the polarization of M2 macrophages in the intestine of Apcmin/+ mice. In conclusion, these data suggested that DCA induced intestinal low grade inflammation and disrupted the mucosal physical and functional barriers, aggravating intestinal tumorigenesis.
- | allopurinol / generics
Journal: NLRP3 inflammasome inhibition ameliorates tubulointerstitial injury in the remnant kidney model. (Pubmed Central) - Mar 29, 2019
...Allopurinol (ALLO) inhibits xanthine oxidase (XOD) activity, and, consequently, reduces the production of uric acid (UA) and reactive oxygen species (ROS), both of which can activate the NLRP3 pathway...ALLO reduced renal NLRP3 activation, without interfering with the NF-κB pathway. These observations indicate that the tubulointerstitial antiinflammatory and antifibrotic effects of ALLO in the Nx model involve inhibition of the NLRP3 pathway, and reinforce the view that ALLO can contribute to arrest or slow the progression of CKD.
- | cisplatin / generics
Preclinical, Journal: Astragaloside IV protects against cisplatin-induced liver and kidney injury via autophagy-mediated inhibition of NLRP3 in rats. (Pubmed Central) - Mar 29, 2019
Autophagy-mediated NLRP3 inhibition might play a crucial role in AS IV-mediated protection against cisplatin-induced toxicity. These results provide evidence of a novel therapeutic that may be used to alleviate the toxic effects of platinum-based chemotherapy.
- | Journal: Some non-sensitizers upregulate CD54 expression by activation of the NLRP3 inflammasome in THP-1 cells. (Pubmed Central) - Mar 29, 2019
CD54 expression, induced by OA and SA, was suppressed by potassium chloride, a typical inhibitor of NLRP3 inflammasome activation. These results suggested that the NLRP3 inflammasome may be activated in THP-1 cells resulting in the expression of CD54, and subsequently leading to false-positive results.
- | Preclinical, Journal: The activation of pyrin domain-containing-3 inflammasome depends on lipopolysaccharide from Porphyromonas gingivalis and extracellular adenosine triphosphate in cultured oral epithelial cells. (Pubmed Central) - Mar 29, 2019
These results suggested that the NLRP3 inflammasome may be activated in THP-1 cells resulting in the expression of CD54, and subsequently leading to false-positive results. The findings indicate that the activation of NLRP3 inflammasome does not rely on P. gingivalis infection, unless stimulated by P. gingivalis LPS and/or extracellular ATP, suggesting diverse signaling pathways are involved in the host immune response.
- | Clinical, Journal: New evidence of connections between increased O-GlcNAcylation and inflammasome in the oral mucosa of patients with oral lichen planus. (Pubmed Central) - Mar 29, 2019
In conclusion, the present study provides supportive evidence that increased O-GlcNAcylation is associated with increased expression of NLRP3 inflammasome via the NF-κB signaling pathway. These findings provide a new perspective on immunopathogenesis of OLP in relation to autoinflammation.
- | Journal: Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway. (Pubmed Central) - Mar 29, 2019
Finally, we showed that pretreatment with IL-1 receptor (IL-1R) antagonist or IL-1R knockdown blocked AF proliferation and differentiation in AFs cultured in PVAT-conditioned medium. These results demonstrate that obesity-induced PVAT dysfunction aggravates adventitial remodeling after early vascular injury with elevated AF proliferation and differentiation via activating the NLRP3/IL-1 signaling pathway.
- | Review, Journal: Anti-Inflammatory Role of TAM Family of Receptor Tyrosine Kinases Via Modulating Macrophage Function. (Pubmed Central) - Mar 28, 2019
In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.
- | Clinical, Journal: Dual Role of PTPN22 but Not NLRP3 Inflammasome Polymorphisms in Type 1 Diabetes and Celiac Disease in Children. (Pubmed Central) - Mar 28, 2019
Interestingly, the same PTPN22 variant protected from CD. We hypothesize that this effect may be mediated through the NLRP3 inflammasome activation.
- | Journal: A new lead to NLRP3 inhibition. (Pubmed Central) - Mar 27, 2019
We hypothesize that this effect may be mediated through the NLRP3 inflammasome activation. The discovery of a small molecule inhibitor that targets the inflammasome sensor NLRP3 offers a new path for the development of selective inflammasome blockers with potential therapeutic benefit in a wide range of human diseases (in this issue, see Jiang et al., https://doi.org/10.1084/jem.20171419).
- | Preclinical, Journal: Gastrodin Alleviates Cognitive Dysfunction and Depressive-Like Behaviors by Inhibiting ER Stress and NLRP3 Inflammasome Activation in db/db Mice. (Pubmed Central) - Mar 27, 2019
Moreover, Gas inhibited ER stress and NLRP3 inflammasome activation in the hippocampus. Taken together, this study demonstrates that Gas attenuates the diabetic encephalopathy by inhibiting ER stress and NLRP3 inflammasome activation.
- | Preclinical, Journal: Purple Sweet Potato Color Attenuates Kidney Damage by Blocking VEGFR2/ROS/NLRP3 Signaling in High-Fat Diet-Treated Mice. (Pubmed Central) - Mar 27, 2019
Purple sweet potato color (PSPC), a natural anthocyanin, can exert renal protection by inhibiting ROS in HFD-treated mice. Here, we provide a novel mechanism of PSPC against renal damage in HFD-treated mice by downregulating VEGFR2 expression.
- | Preclinical, Journal: Antidepressant-like Effects Induced by Chronic Blockade of the Purinergic 2X7 Receptor through Inhibition of Non-like Receptor Protein 1 Inflammasome in Chronic Unpredictable Mild Stress Model of Depression in Rats. (Pubmed Central) - Mar 26, 2019
Chronic administration of BBG in CUMS model results in antidepressant-like activity in a dose dependent manner. Molecular and histological results show that these effects might be at least partially related to the suppression of inflammasome-related neuroinflammatory responses and suggest involvement of NLRP1 in depression.
- | metformin / generics
Journal: Metformin induces the M2 macrophage polarization to accelerate the wound healing via regulating AMPK/mTOR/NLRP3 inflammasome singling pathway. (Pubmed Central) - Mar 24, 2019
Metformin regulated AMPK/mTOR singling pathway to inhibit NLRP3 inflammasome activation, which boosted M2 macrophage polarization to accelerate the wound healing. These findings provided new insights into the molecular mechanism of metformin therapy and its therapeutic potential in wound healing.
- | Journal: SXBX pill suppresses homocysteine-induced vascular smooth muscle cells dedifferentiation by inhibiting NLRP3 inflammasomes activation via ERK/p38 MAPK pathways. (Pubmed Central) - Mar 24, 2019
Knockdown of NLRP3 reversed the inhibitory effects of SXBX pill in VSMCs. In conclusion, SXBX pill inhibited Hcy-induced proliferation, migration and dedifferentiation of VSMCs by suppressing NLRP3 inflammasomes activation via of ERK/p38 MAPK pathway.
- | fimasartan (BR-A-657) / Boryung Group
Journal: Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage. (Pubmed Central) - Mar 23, 2019
Pretreatment with a low-dose fimasartan alleviated brain damage after acute ICH by inhibiting the NLRP3 inflammasome without lowering MBP. Our study suggests pre-stroke administration of fimasartan could potentially attenuate ICH-induced secondary brain injury by targeting the inflammasome.
- | Journal, IO Biomarker: Inducible Nitric Oxide Synthase Is a Key Host Factor for Toxoplasma GRA15-Dependent Disruption of the Gamma Interferon-Induced Antiparasitic Human Response. (Pubmed Central) - Mar 23, 2019
Here, we show that GRA15, a Toxoplasma effector protein, suppresses the IFN-γ-induced indole-2,3-dioxygenase 1-dependent antiparasite immune response in human cells. Because NLRP3-dependent production of IL-1β and nitric oxide (NO) in Toxoplasma-infected human cells is involved in the GRA15-dependent virulence mechanism, blocking NO or IL-1β production in the host could represent a novel therapeutic approach for treating human toxoplasmosis.
- | Journal: Klotho controls the brain-immune system interface in the choroid plexus. (Pubmed Central) - Mar 23, 2019
We conclude that klotho functions as a gatekeeper at the interface between the brain and immune system in the choroid plexus. Klotho depletion in aging or disease may weaken this barrier and promote immune-mediated neuropathogenesis.
- | Journal: Increased HIF-1α in Knee Osteoarthritis Aggravate Synovial Fibrosis via Fibroblast-Like Synoviocyte Pyroptosis. (Pubmed Central) - Mar 6, 2019
Taken together, our findings indicate that increased HIF-1α is highly involved in the KOA synovial fibrosis. Moreover, elevated HIF-1α may aggravate synovial fibrosis via FLS pyroptosis.
- | Journal: Mediterranean Diet, Glucose Homeostasis and Inflammasome Genetic Variants: The CORDIOPREV Study. (Pubmed Central) - Jan 19, 2019
Moreover, elevated HIF-1α may aggravate synovial fibrosis via FLS pyroptosis. Our results show that the benefits associated with a Mediterranean diet regarding glucose homeostasis in non-T2DM patients depend on genetic variation in the inflammasome.
- | Onglyza (saxagliptin) / AstraZeneca, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Preclinical, Journal: Combined SGLT2 and DPP4 Inhibition Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Nephropathy in Mice with Type 2 Diabetes. (Pubmed Central) - Jan 17, 2019
Adding Saxa to Dapa augmented attenuation of the inflammasome, but had no significant effect on kidney weight or collagen-1 and collagen-3 mRNA levels. Future clinical trials are necessary to study the effect of combined SGLT2 inhibitor and incretin therapy on renal outcomes in patients with T2DM.
- | Journal: Microbial metabolite sensor GPR43 controls severity of experimental GVHD. (Pubmed Central) - Jan 8, 2019
The GVHD protective effect of SCFAs requires GPR43-mediated ERK phosphorylation and activation of the NLRP3 inflammasome in non-hematopoietic target tissues of the host. These data provide insight into mechanisms of microbial metabolite-mediated protection of target tissues from the damage caused allogeneic T cells.
- | belnacasan (VX-765) / Vertex
Journal: Roles of mitochondrial ROS and NLRP3 inflammasome in multiple ozone-induced lung inflammation and emphysema. (Pubmed Central) - Jan 4, 2019
These data provide insight into mechanisms of microbial metabolite-mediated protection of target tissues from the damage caused allogeneic T cells. Both mtROS and NLRP3 inflammasome play a role in ozone-induced lung inflammation while only NLRP3 is involved in ozone-induced emphysema.
- | Biomarker, Observational data, Journal: Assessment of ASC specks as a putative biomarker of pyroptosis in myelodysplastic syndromes: an observational cohort study. (Pubmed Central) - Nov 27, 2018
Both mtROS and NLRP3 inflammasome play a role in ozone-induced lung inflammation while only NLRP3 is involved in ozone-induced emphysema. Our results underscore the pathobiological relevance of ASC specks and suggest that ASC specks are a sensitive and specific candidate plasma biomarker that provides an index of medullary pyroptotic cell death and ineffective haemopoiesis in patients with myelodysplastic syndromes.