scholarly journals Targeted Inhibition of FTO Demethylase Protects Mice Against LPS-Induced Septic Shock by Suppressing NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahui Luo ◽  
Faxi Wang ◽  
Fei Sun ◽  
Tiantian Yue ◽  
Qing Zhou ◽  
...  
Keyword(s):  
Septic Shock ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Endotoxic Shock ◽  
Sirna Delivery ◽  
Clinical Problem ◽  
Targeted Inhibition ◽  
Major Clinical Problem

Sepsis refers to the systemic inflammatory response syndrome caused by infection. It is a major clinical problem and cause of death for patients in intensive care units worldwide. The Fat mass and obesity-related protein (FTO) is the primary N6-methyladenosine demethylase. However, the role of FTO in the pathogenesis of inflammatory diseases remains unclear. We herein show that nanoparticle-mediated Fto-siRNA delivery or FTO inhibitor entacapone administration dramatically inhibited macrophage activation, reduced the tissue damage and improved survival in a mouse model of LPS-induced endotoxic shock. Importantly, ablation of FTO could inhibit NLRP3 inflammasome through FoxO1/NF-κB signaling in macrophages. In conclusion, FTO is involved in inflammatory response of LPS-induced septic shock and inhibition of FTO is promising for the treatment of septic shock.

Epidemiology and antimicrobial resistance of Acinetobacter

2018 ◽  
Vol 2 (4) ◽  
pp. 46-59
Author(s):  
A.G. Salmanov ◽  
O.M. Verner ◽  
L.F. Slepova
Keyword(s):  
Antibiotic Resistance ◽  
Laboratory Testing ◽  
Immunocompromised Host ◽  
Clinical Problem ◽  
Healthcare Associated Infections ◽  
Opportunistic Bacteria ◽  
Acinetobacter Spp ◽  
Healthcare Associated ◽  
Major Clinical Problem

Species of the Acinetobacter represent opportunistic bacteria with a growing clinical significance for Healthcare-associated infections (HAIs). In this literature review, we focus on the current role of Acinetobacter in infectious pathology and describe taxonomy, pathogenicity, and antibiotic resistance of these bacteria. Pathogenesis and regulation of virulence factors in Acinetobacter spp. are described in detail. The majority of acinetobacterial infections are associated with A. baumannii and occur predominantly in an immunocompromised host. Usually, acinetobacterial  infections  are characterized by local purulent inflammation; in severe cases, meningitis and sepsis may develop. Antibiotic resistance of Acinetobacter is a major clinical problem; therefore we give special attention to laboratory testing of resistance to antibiotics as well as identification of Acinetobacter.

scholarly journals The Beneficial Effect of Direct Peritoneal Resuscitation on Septic Shock in Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Xingjun Luo ◽  
Daolin Jian ◽  
Zuojun Lv
Keyword(s):  
Septic Shock ◽  
Inflammatory Response ◽  
Beneficial Effect ◽  
Multiple Organ Failure ◽  
Hemorrhagic Shock ◽  
Clinical Problem ◽  
Multiple Organ ◽  
Cellular Viability ◽  
Internal Organs ◽  
Organ Systems

The high mortality associated with conventionally resuscitated septic shock and the subsequent multiple-organ failure remain a very significant and costly clinical problem. Conventional simple intravenous resuscitation (CR) from septic shock often fails to restore the progressive splanchnic vasoconstriction and hypoperfusion, and fails to reverse gut-derived systemic inflammatory response and fluid sequestration. Numerous interventions have been used to protect organ systems and cellular viability from the lethal injury accompanying hypoperfusion and ischemia but none of these efforts have been sufficient to halt or reverse the main course of the pathophysiology noted with conventional resuscitated shock. Recently, some studies have found that in hemorrhagic shock, direct peritoneal resuscitation (DPR) not only produces sustained hyperperfusion in viscera but also has immunomodulatory and anti-fluid sequestration effects. Although the etiology and pathogenesis of septic shock and hemorrhagic shock differ, both kinds of shock result in hypoperfusion of the intestines and other internal organs. In this paper, we seek to determine whether DPR has a similar therapeutic effect on septic shock/resuscitation.

scholarly journals The Role of Poly(ADP-ribose) Polymerase-1 in Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Samuel García ◽  
Carmen Conde
Keyword(s):  
Rheumatoid Arthritis ◽  
Septic Shock ◽  
Dna Repair ◽  
Beneficial Effect ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Genomic Stability ◽  
Inflammatory Processes ◽  
Parp 1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis.

scholarly journals Inhibitory Role of Berberine, an Isoquinoline Alkaloid, on NLRP3 Inflammasome Activation for the Treatment of Inflammatory Diseases

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6238
Author(s):  
Paromita Sarbadhikary ◽  
Blassan P. George ◽  
Heidi Abrahamse
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
In Vivo Studies ◽  
Inflammasome Activation ◽  
Inflammatory Disorders ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

The pyrin domain-containing multiprotein complex NLRP3 inflammasome, consisting of the NLRP3 protein, ASC adaptor, and procaspase-1, plays a vital role in the pathophysiology of several inflammatory disorders, including neurological and metabolic disorders, chronic inflammatory diseases, and cancer. Several phytochemicals act as promising anti-inflammatory agents and are usually regarded to have potential applications as complementary or alternative therapeutic agents against chronic inflammatory disorders. Various in vitro and in vivo studies have reported the anti-inflammatory role of berberine (BRB), an organic heteropentacyclic phytochemical and natural isoquinoline, in inhibiting NLRP3 inflammasome-dependent inflammation against many disorders. This review summarizes the mechanism and regulation of NLRP3 inflammasome activation and its involvement in inflammatory diseases, and discusses the current scientific evidence on the repressive role of BRB on NLRP3 inflammasome pathways along with the possible mechanism(s) and their potential in counteracting various inflammatory diseases.

scholarly journals Downregulation of ALDH5A1 Promotes Tumor Metastasis and Contributes to Poor Prognosis in Ovarian Cancer

2020 ◽  
Author(s):  
Chen Cao ◽  
Xin Wang ◽  
Rui Li ◽  
Ping Jin ◽  
Hongwei Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Expression Profile ◽  
Poor Prognosis ◽  
Tumor Metastasis ◽  
Clinical Problem ◽  
Primary Site ◽  
Oncomine Database ◽  
Risk Of Mortality ◽  
Major Clinical Problem

Abstract Background Despite modern therapies, ovarian cancer (OC) remains a major clinical problem with a high risk of mortality. We previously reported that low expression of ALDH5A1 could serve as an indicator for predicting poor prognosis in OC. However, the function of ALDH5A1 in OC progression has not been elucidated yet. Methods We firstly compared ALDH5A1 expression in metastatic tissues to primary site of OC based on the Oncomine database. Then wound healing assay and Transwell assay were utilized to determine the biological role of OC cells transfected with ALDH5A1 siRNA. To unravel the potential mechanism of ALDH5A1 meditating metastasis of OC, the co-expression profile of ALDH5A1 in OC cell lines and OC patients were generated using cBioPortal. Moreover, qRT-PCR and WB analysis were used to detect the expression levels of metastasis-related genes after ALDH5A1 suppression, HPA database was used to confirm the relative expression of ALDH5A1 and MMP in OC patients. In addition, KM survival plots in 578 OC patients from the TCGA database were analyzed. Results We proved lower ALDH5A1 expression in metastatic tissues compared to primary site of OC, and knockdown of ALDH5A1 promoted the malignant behavior of OC cells. Additionally, the co-expression profile of ALDH5A1 was significantly enriched in extracellular matrix (ECM) organization pathway. We further confirmed ALDH5A1 was negatively associated with MMP expression in OC, indicating that ALDH5A1 was closely related to OC metastasis via ECM organization pathway. Finally, KM survival plots revealed that low ALDH5A1 expression contributed to poor OC survival. Conclusions These results suggested a key role of ALDH5A1 in driving the progression of OC and identified ALDH5A1 as a robust therapeutic target of OC.

scholarly journals The Role of HDAC6 in Autophagy and NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Chang ◽  
Hao Li ◽  
Hui Hu ◽  
Yongqing Li ◽  
Tianbing Wang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Histone Deacetylase 6 ◽  
Physiological Processes ◽  
Class Iib ◽  
Underlying Mechanisms ◽  
Nlrp3 Inflammasomes ◽  
Insight Into

Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1β/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy and NLRP3 inflammasome in multifaceted ways to influence host defense and inflammation. However, the underlying mechanisms require further clarification. Histone deacetylase 6 (HDAC6) is a class IIb deacetylase among the 18 mammalian HDACs, which mainly localizes in the cytoplasm. It is involved in two functional deacetylase domains and a ubiquitin-binding zinc finger domain (ZnF-BUZ). Due to its unique structure, HDAC6 regulates various physiological processes, including autophagy and NLRP3 inflammasome, and may play a role in the crosstalk between them. In this review, we provide insight into the mechanisms by which HDAC6 regulates autophagy and NLRP3 inflammasome and we explored the possibility and challenges of HDAC6 in the crosstalk between autophagy and NLRP3 inflammasome. Finally, we discuss HDAC6 inhibitors as a potential therapeutic approach targeting either autophagy or NLRP3 inflammasome as an anti-inflammatory strategy, although further clarification is required regarding their crosstalk.

scholarly journals Sinapic Acid Controls Inflammation by Suppressing NLRP3 Inflammasome Activation

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2327
Author(s):  
Eun Hye Lee ◽  
Jin Hak Shin ◽  
Seon Sook Kim ◽  
Su Ryeon Seo
Keyword(s):  
Cinnamic Acid ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Endotoxic Shock ◽  
Sinapic Acid ◽  
Inflammasome Activation ◽  
Cinnamic Acid Derivative ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Anti Inflammatory

A natural phenolic acid compound, sinapic acid (SA), is a cinnamic acid derivative that contains 3,5-dimethoxyl and 4-hydroxyl substitutions in the phenyl ring of cinnamic acid. SA is present in various orally edible natural herbs and cereals and is reported to have antioxidant, antitumor, anti-inflammatory, antibacterial, and neuroprotective activities. Although the anti-inflammatory function of SA has been reported, the effect of SA on the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome has not been explored. In the present study, to elucidate the anti-inflammatory mechanism of SA, we examined whether SA modulates the NLRP3 inflammasome. We found that SA blocked caspase-1 activation and IL-1β secretion by inhibiting NLRP3 inflammasome activation in bone marrow-derived macrophages (BMDMs). Apoptosis-associated speck-like protein containing CARD (ASC) pyroptosome formation was consistently blocked by SA treatment. SA specifically inhibited NLRP3 activation but not the NLRC4 or AIM2 inflammasomes. In addition, SA had no significant effect on the priming phase of the NLRP3 inflammasome, such as pro-IL-1β and NLRP3 inflammasome expression levels. Moreover, we found that SA attenuated IL-1β secretion in LPS-induced systemic inflammation in mice and reduced lethality from endotoxic shock. Our findings suggest that the natural compound SA has potential therapeutic value for the suppression of NLRP3 inflammasome-associated inflammatory diseases.

Plantamajoside Ameliorates Inflammatory Response of Chondrocytes via Regulating NF-κB/NLRP3 Inflammasome Pathway

2021 ◽  
Vol 11 (5) ◽  
pp. 997-1002
Author(s):  
Chi Zhang ◽  
Yuanhe Wang ◽  
Chuan Hu ◽  
Kang Sun ◽  
Dingzhu Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cell Viability ◽  
Nlrp3 Inflammasome ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Enzyme Linked Immunosorbent Assay ◽  
Apoptotic Cells ◽  
Protein Levels

The damage of articular cartilage in osteoarthritis involves the oxidative stress and inflammation. The aim of the present study was to explore the role of plantamajoside (PM) in chondrocytes and elucidate the underlying mechanism. The cell viability following treatment with PM or lipopolysac-charide (LPS) was assessed by cell counting kit-8 (CCK-8). Enzyme-Linked Immunosorbent Assay (ELISA) was supplied to determine the levels of pro-inflammatory cytokines. Moreover, the oxidative stress-related markers were evaluated via assay kits. TUNEL assay was employed to stain the apoptotic cells. The components of nuclear factor-κB (NF-κB) pathway and NLRP3 inflammasome were estimated by western blot analysis. LPS-insulted cell viability of ATDC5 was restored by PM. PM alleviated the inflammatory response and oxidative stress of ATDC5 cells induced by LPS. Furthermore, it was found that the apoptotic cells were reduced following PM treatment. The protein levels of NF-κB, IκB kinase β (IKKβ) and NLRP3 inflammasome were decreased by PM. These results suggested that PM protected the ATDC5 cells from LPS stimulation, alleviated the inflammatory response may through regulating the NF-κB and NLRP3 inflammasome.

NLRP3 inflammasome is involved in uterine activation for labor at term and preterm

Reproduction ◽  
2021 ◽  
Vol 162 (6) ◽  
pp. 449-460
Author(s):  
Zixi Chen ◽  
Yali Shan ◽  
Xingji You ◽  
Hang Gu ◽  
Chen Xu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Inflammasome Activation ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Pregnant Mice ◽  
Labor Onset

The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in various inflammatory diseases. We sought to investigate the role of NLRP3 inflammasome in uterine activation for labor at term and preterm. We found that NLRP3 inflammasome was activated in the myometrium tissues obtained from the pregnant women undergoing labor at term (TL) compared with those not undergoing labor (TNL) at term. NLRP3 inflammasome was also activated in amnion and chorion-deciduas in TL and preterm labor (PTL) groups. In the mouse model, uterine NLRP3 inflammasome and nuclear factor kappaB (NF-κB) were activated toward term and during labor. Treatment of pregnant mice with lipopolysaccharide (LPS) and RU38486 induced preterm birth (PTB) and also promoted uterine NLRP3 inflammasome and NF-κB activation. Treatment of pregnant mice with NLRP3 inflammasome inhibitor BAY11-7082 and MCC950 delayed the onset of labor and suppressed NLRP3 inflammasome and NF-κB activation in uterus. MCC950 postponed labor onset of the mice with LPS and RU38486 treatment and inhibited NLRP3 inflammasome activation in uterus. Our data provide the evidence that NLRP3 inflammasome is involved in uterine activation for labor onset in term and PTB in humans and mouse model.

scholarly journals Interaction between autophagy and the NLRP3 inflammasome

2019 ◽  
Vol 51 (11) ◽  
pp. 1087-1095 ◽  
Author(s):  
Zhenrui Cao ◽  
Yanhao Wang ◽  
Zhimin Long ◽  
Guiqiong He
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Dynamic Balance ◽  
Cell Structure ◽  
Innate Immune ◽  
Interleukin 18 ◽  
Disease Treatment ◽  
Selective Autophagy ◽  
Inflammatory Bowel

Abstract Autophagy, a metabolic pathway that plays an important role in maintaining the dynamic balance of cells, has two types, i.e. non-selective autophagy and selective autophagy. The role of non-selective autophagy is primarily to allow cells to circulate nutrients in an energy-limited environment, while selective autophagy primarily cleans up the organelles inside the cells to maintain the cell structure. The NLRP3 inflammasome is an innate immune response produced by the organism that can promote the secretion of interleukin-1β and interleukin-18 through caspase-1 activation and resist the damage of some pathogens. However, when the NLRP3 inflammasome is overactivated, it can cause various inflammatory diseases, such as inflammatory liver disease and inflammatory bowel disease. Many previous studies have shown that autophagy can inhibit the NLRP3 inflammasome, while in recent years, new studies have found that autophagy can also promote the NLRP3 inflammasome in some cases, and the NLRP3 inflammasome can, in turn, affect autophagy. In this review, the interaction between autophagy and the NLRP3 inflammasome is explored, and then the application of this interaction in disease treatment is discussed.

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