Search Results (114)

Chronic inflammation plays a central role in the progression and complications of chronic kidney disease (CKD). The nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome pathway has emerged as a crucial mediator of the inflammatory response in CKD. This cross-sectional study evaluated the expression of NLRP3 in patients with CKD undergoing different treatments. Blood samples were collected from 32 non-dialysis (ND) patients [63 (11.2) years, estimated glomerular filtration rate, 43.5 (22.0) mL/min, BMI, 29.5 (10.0) kg/m²)], 50 hemodialysis (HD) patients [48.5 (16.5) years, 60.5 (50) months on HD, BMI, 24.2 (4.9) kg/m²)], and 8 peritoneal dialysis (PD) patients [56.5 (8.5) years, 40.5 (41.2) months on PD, BMI, 28.8 (2.6) kg/m²)]. The mRNA expression level of NLRP3 was measured using real-time PCR. The cytokines and the malondialdehyde (MDA) levels were also assessed. The results indicated that the mRNA level of NLRP3 was significantly elevated in patients undergoing HD (1.23, IQR = 0.95) compared with that in non-dialysis patients (0.79, IQR = 0.35) and in patients undergoing PD (0.77, IQR = 0.38) after adjusting for confounding variables, including age, sex, BMI, and dialysis duration. Furthermore, the MDA levels were significantly higher in HD patients. NLRP3 is upregulated in HD patients, and the results suggested that the inflammasome may be associated with oxidative stress in patients with CKD. Full article

Cognitive problems are associated with impaired learning ability and memory dysfunction. Neuroinflammation has been identified as an important factor in the progression of anxiety and depressive disorders. Zingerone is a phenolic alkanone derived from ginger (Zingiber officinale Roscoe), which is known for its antioxidant and anti-inflammatory properties. A number of studies have investigated the effect of zingerone on neuroinflammation and cognitive impairment. However, this evidence has not been systematically reviewed. This study sought to systematically review the effect of zingerone on neuroinflammation and neurobehavioural changes associated with memory and learning impairment and anxiety-like and depressive-like behaviours. A systematic review was conducted using pre-defined search criteria on Google Scholar, Scopus and Web of Science. The records obtained were screened based on inclusion criteria, and data was extracted from the included studies. Out of the 482 studies that were identified, only 9 studies met the inclusion criteria. Neuroinflammatory markers such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumour necrosis factor-alpha (TNF-α) and ionized calcium binding adaptor molecule (IBA-1), as well as behavioural parameters including Morris water maze, Y-Maze, recognition test, passive avoidance test, elevated plus maze, sucrose preference test and forced swimming test were measured. Zingerone exhibited anti-neuroinflammatory effects by improving IL-1β, IL-6 and TNF-α levels. However, zingerone did not show any significant changes on activated microglia. The anti-neuroinflammatory mechanisms of zingerone were linked to the inhibition of nuclear factor kappa B (NF-kB) activation and the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, as well as the reduction in neuronal nitric oxide synthase (nNOS). The anxiolytic and anti-depressive effects of zingerone were also associated with an improvement in cortical cholinergic transmission, the mitigation of oxidative stress and the upregulation of neurotransmitters such as serotonin and dopamine. This review provides scientific evidence on the cognitive enhancing and neuroprotective mechanisms of zingerone, which may be beneficial for future experimental investigations. Full article

This study investigates the anti-inflammatory effects of the marine diterpene glycosides pseudopterosin A-D (PsA-D) in mitigating nickel sulfate (NiSO₄)-induced skin sensitization. In dermal dendritic cell (DDC) surrogates, PsA-D pre-treatment significantly reduced NiSO₄-induced upregulation of key activation surface markers, cluster of differentiation (CD)54 (~1.2-fold), and CD86 (~1.6-fold). Additionally, PsA-D inhibited the NiSO₄-induced activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway by suppressing inhibitor of kappa B alpha (IκBα) degradation. Furthermore, PsA-D suppressed inflammatory responses by inhibiting the NiSO₄-induced secretion of pro-inflammatory cytokines, including interleukin (IL)-8 (~6.8-fold), IL-6 (~2.2-fold), and IL-1β (~5.3-fold). In a full-thickness human skin model incorporating DDC surrogates, topical application of PsA-D effectively attenuated NiSO₄-induced mRNA expression of IL-8 (~2.1-fold), IL-6 (~2.6-fold), and IL-1β (~2.2-fold), along with the key inflammatory mediators cyclooxygenase-2 (COX-2) (~3.5-fold) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) (~2.1-fold). Overall, PsA-D demonstrated comparable efficacy to dexamethasone, a benchmark corticosteroid, providing a promising therapeutic alternative to corticosteroids for the treatment of skin sensitization and allergic contact dermatitis. However, to maximize PsA-D’s therapeutic potential, future studies on optimizing the bioavailability and formulation of PsA-D are required. Full article

Deregulation of microRNAs (miRNAs) has been implicated in the development of inflammatory bowel disease (IBD). Specific miRNAs are differentially expressed in patients with IBD compared to healthy individuals. Regulation of their expression can modulate the inflammatory response, the composition of the intestinal microbiota, and intestinal barrier function. miRNAs can regulate the immune and inflammatory response via multiple mechanisms, from Th1/Th17 regulation and ferroptosis to modulation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) and control of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway. The use of miRNAs as biomarkers and therapeutic targets may help monitor IBD treatment and support the development of new, more individualized therapies that minimize common side effects. Full article

Infection with influenza A virus (IAV) may trigger excessive inflammatory responses, leading to severe viral pneumonia and accelerating disease progression. Therefore, controlling these excessive inflammatory responses is crucial for the prevention and treatment of pneumonia caused by IAV. Berberine (BBR), an isoquinoline alkaloid extracted from traditional Chinese medicine, possesses extensive pharmacological activities. However, its immunoregulatory effects and molecular mechanisms in the context of IAV infection require further investigation. This study explored the impact of BBR on macrophage pyroptosis and inflammatory responses induced by IAV infection. Our findings revealed that BBR effectively inhibits the release of IL-1β and TNF-α induced by IAV infection and suppresses gasdermin D (GSDMD)-mediated pyroptosis in a dose-dependent manner. Further research indicates that BBR alleviates macrophage pyroptosis and inflammatory responses in IAV-infected cells by reducing the release of mitochondrial reactive oxygen species (mtROS), inhibiting mitochondrial antiviral signaling protein (MAVS) expression and blocking the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Experiments using siRNA to knockdown MAVS further confirmed the pivotal role of MAVS in BBR’s inhibition of IAV-induced macrophage pyroptosis. This study provides a scientific basis for the application of BBR as an anti-inflammatory drug in the treatment of inflammatory diseases caused by IAV infection and directs future research endeavors. Full article

While the beneficial effects of colchicine on inflammation and infarcted myocardium have been documented, its impact on cardiac fibroblast activation in the context of myocardial infarction (MI) remains unknown. This study aimed to investigate the effect of colchicine on the regulation of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and Interleukin-1β (IL-1β) expression in fibroblasts. 3T3 fibroblasts were exposed to 600 μM CoCl₂ for 24 h to simulate hypoxia, with normoxic cells as controls. Colchicine (1 μM) was administered for 24 h. ASC-NLRP3 colocalization and IL-1β expression were evaluated using immunofluorescence and flow cytometry, respectively. Data were analyzed using t-tests and one-way ANOVA with post hoc tests. Hypoxia treatment significantly induced apoptosis-associated speck-like protein containing a CARD (ASC)-NLRP3 colocalization (p < 0.05). Colchicine treatment of hypoxic 3T3 cells reduced ASC-NLRP3 colocalization, although this reduction was not statistically significant. Additionally, IL-1β expression was significantly inhibited in colchicine-treated hypoxic 3T3 cells compared to those treated with placebo (p < 0.05). The findings of this study indicate that colchicine treatment inhibits the activation of the NLRP3 inflammasome by disrupting the colocalization of ASC and NLRP3, thereby reducing IL-1β expression in CoCl₂-treated 3T3 cells. Full article

Aside from its immediate traumatic effects, spinal cord injury (SCI) presents multiple secondary complications that can be harmful to those who have been affected by SCI. Among these secondary effects, gut dysbiosis (GD) and the activation of the NOD (nucleotide-binding oligomerization domain) like receptor-family pyrin-domain-containing three (NLRP3) inflammasome are of special interest for their roles in impacting mental health. Studies have found that the state of the gut microbiome is thrown into disarray after SCI, providing a chance for GD to occur. Metabolites such as short-chain fatty acids (SCFAs) and a variety of neurotransmitters produced by the gut microbiome are hampered by GD. This disrupts healthy cognitive processes and opens the door for SCI patients to be impacted by mental health disorders. Additionally, some studies have found an increased presence and activation of the NLRP3 inflammasome and its respective parts in SCI patients. Preclinical and clinical studies have shown that NLRP3 inflammasome plays a key role in the maturation of pro-inflammatory cytokines that can initiate and eventually aggravate mental health disorders after SCI. In addition to the mechanisms of GD and the NLRP3 inflammasome in intensifying mental health disorders after SCI, this review article further focuses on three promising treatments: fecal microbiome transplants, phytochemicals, and melatonin. Studies have found these treatments to be effective in combating the pathogenic mechanisms of GD and NLRP3 inflammasome, as well as alleviating the symptoms these complications may have on mental health. Another area of focus of this review article is exploring how artificial intelligence (AI) can be used to support treatments. AI models have already been developed to track changes in the gut microbiome, simulate drug-gut interactions, and design novel anti-NLRP3 inflammasome peptides. While these are promising, further research into the applications of AI for the treatment of mental health disorders in SCI is needed. Full article

The side effects associated with the chemotherapy of triple-negative breast cancer (TNBC), such as nucleotide-binding oligomerization domain (NOD)-like receptor family (NLR), pyrin domain containing 3 (NLRP3) inflammasome activity, are responsible for the treatment failure and high mortality rates. Therefore, advanced delivery systems have been developed to improve the transport and targeted administration of anti-tumor agents at the tumor sites using tissue engineering approaches. Implantable delivery systems based on biodegradable polymers are an effective alternative due high biocompatibility, porosity, and mechanical strength. Moreover, the use of paclitaxel (PTX)-cyclodextrin complexes increases the solubility and permeability of PTX, enhancing the bioavailability and efficacy of the drug. All of these properties contribute to the efficient encapsulation and controlled release of drugs, preventing the damage of healthy tissues. In the current study, we detailed the synthesis process and evaluation of 3D scaffolds based on gelatin functionalized with methacryloyl groups (GelMA) and pectin loaded with PTX–cyclodextrin inclusion complexes on TNBC pathogenesis in vitro and in vivo. Bio-physio-chemical analysis of the proposed scaffolds revealed favorable mechanical and biological properties for the cellular component. To improve the drug solubility, a host–guest interaction was performed by the complexation of PTX with a cyclodextrin derivative prior to scaffold synthesis. The presence of PTX suppressed the growth of breast tumor cells and promoted caspase-1 activity, the release of interleukin (IL)-1β, and the production of reactive oxygen species (ROS), conditioning the expression levels of the genes and proteins associated with breast tumorigenesis and NLRP3 inflammasome. The in vivo experiments suggested the activation of pyroptosis tumor cell death, confirming the in vitro experiments. In conclusion, the bio-mechanical properties of the GelMA and pectin-based scaffolds as well as the addition of the PTX–cyclodextrin complexes allow for the targeted and efficient delivery of PTX, suppressing the viability of the breast tumor cells via pyroptosis cell death initiation. Full article

Atherosclerosis, a chronic inflammatory disease, is driven by complex molecular mechanisms involving inflammatory cytokines and immune pathways. According to recent research, tricyclic antidepressants (TCAs), which are typically prescribed to treat depressive disorders, have strong anti-inflammatory effects. TCAs, including imipramine and amitriptyline, alter inflammatory signaling cascades, which include lowering the levels pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6 and inhibiting NF-κB activation. By inhibiting the NLRP3 inflammasome and suppressing pathways including JAK/STAT, MAPK, and PI3K, these effects are produced, improving endothelial function and reducing oxidative stress. The intricacy of TCAs’ anti-inflammatory actions has demonstrated by the existence of contradictory findings about how they alter IL-6 levels. The dependence of the heterogeneity of the reaction on the use of particular TCAs and experimental settings is shown by the fact that some studies show reduced IL-6 production, while others indicate increases or no changes. This review explores the multifaceted mechanisms through which TCAs modulate inflammatory pathways. TCAs inhibit NF-κB activation, reduce oxidative stress, and suppress the production of key inflammatory mediators, including IL-6 and TNF-α. They also regulate Toll-like receptor (TLR) signaling and NOD-, LRR-, and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome activation, reducing the release of IL-1β and IL-18, critical drivers of endothelial dysfunction and plaque instability. Given their capacity to target critical inflammatory molecules and pathways, TCAs provide great potential in the therapy of atherosclerosis, particularly for individuals with associated depression and cardiovascular risk factors. Nevertheless, further research is essential to clarify the precise molecular mechanisms, resolve inconsistencies in current findings, and establish the clinical applicability of TCAs as anti-inflammatory agents in atherosclerosis management. Full article

Current knowledge about Alzheimer’s disease highlights the accumulation of β-amyloid plaques (Aβ1–42) and neurofibrillary tangles composed of hyperphosphorylated Tau, which lead to the loss of neuronal connections. Microglial activation and the release of inflammatory mediators play a significant role in the progression of Alzheimer’s pathology. Recent advances have identified the involvement of inflammasomes, particularly NOD-like receptor NLR family pyrin domain containing 3 (NLRP3), whose activation promotes the release of proinflammatory cytokines and triggers pyroptosis, exacerbating neuroinflammation. Aggregates of Aβ1–42 and hyperphosphorylated Tau have been shown to activate these inflammasomes, while the apoptosis-associated speck-like protein (ASC) components form aggregates that further accelerate Aβ aggregation. Defects in the autophagic clearance of inflammasomes have also been implicated in Alzheimer’s disease, contributing to sustained inflammation. This review explores strategies to counteract inflammation in Alzheimer’s, emphasizing the degradation of ASC specks and the inhibition of NLRP3 inflammasome activation. Notably, the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor emerges as a promising therapeutic target due to its dual role in mitigating oxidative stress and directly inhibiting NLRP3 inflammasome formation. By reducing inflammasome-driven inflammation, Nrf2 offers significant potential for addressing the neuroinflammatory aspects of Alzheimer’s disease. Full article

Background/Objectives: Cutibacterium acnes (C. acnes), a bacterium residing in hair follicles, triggers acne by inducing monocyte-mediated inflammatory cytokine production. Gedunin, a limonoid derived from Azadirachta indica (commonly known as neem), is renowned for its antifungal, antimalarial, anticancer, anti-inflammatory, and neuroprotective effects. However, its role in mitigating C. acnes-induced skin inflammation remains unexplored. This study investigates the anti-inflammatory effects of gedunin on C. acnes-induced skin inflammation and elucidates the underlying mechanisms. Methods: The anti-inflammatory activity of gedunin was assessed using RAW 264.7 mouse macrophage cells and mouse bone-marrow-derived macrophages (BMDMs). Key inflammatory mediators, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin-6 (IL-6), were evaluated. Mechanistic studies focused on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, along with the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome. An in vivo acne model was employed to examine gedunin’s therapeutic efficacy. Results: Gedunin significantly reduced the expression of IL-1β, TNF-α, iNOS, COX-2, and IL-6 in RAW 264.7 cells. It inhibited NF-κB activation without affecting the MAPK pathways, including JNK/SAPK, ERK, and p38 MAPK. Gedunin also suppressed the activation of the NLRP3 inflammasome in BMDMs. In the mouse acne model, gedunin effectively alleviated C. acnes-induced inflammation, primarily by targeting NF-κB signaling. Conclusions: Gedunin demonstrates potential as a therapeutic agent for acne treatment by targeting key inflammatory pathways, particularly NF-κB signaling. This study highlights gedunin’s promise as an alternative approach to managing C. acnes-induced skin inflammation. Full article

Polycystic ovarian syndrome (PCOS) is a multifaceted metabolic and hormonal disorder in females of reproductive age, frequently associated with cardiac disturbances. This research aimed to explore the protective potential of adropin and/or tirzepatide (Tirze) on cardiometabolic aberrations in the letrozole-induced PCOS model. Female Wistar non-pregnant rats were allotted into five groups: CON; PCOS; PCOS + adropin; PCOS + Tirze; and PCOS + adropin+ Tirze. The serum sex hormones, glucose, and lipid profiles were securitized. Cardiac phosphorylated levels of AKT(pAKT), glycogen synthase kinase-3 beta (pGSK-3β), NOD-like receptor family pyrin domain containing 3 (NLPR3), IL-1β and IL-18 were assayed. The cardiac redox status and endoplasmic reticulum stress (ER) parameters including relative glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) gene expressions were detected. Finally, the immunoreactivity of cardiac NF-κB, Bcl2, and BAX were assessed. Our results displayed that adropin and/or Tirze intervention successfully alleviated the PCOS-provoked cardiometabolic derangements with better results recorded for the combination treatment. The synergistic effect of adropin and Tirze is mostly mediated via activating the cardiac Akt, which dampens the GSK3β/NF-κB/NLRP3 signaling pathway, with a sequel of alleviating oxidative damage, inflammatory response, ER stress, and related apoptosis, making them alluring desirable therapeutic targets in PCOS-associated cardiac complications. Full article

Acute pancreatitis (AP) remains a serious clinical condition, with current treatment options being largely supportive. The discovery of inflammasomes, particularly the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, has significantly advanced our knowledge regarding many inflammatory diseases’ pathogenesis, including AP. The NLRP3 inflammasome is central in mediating the inflammatory process in AP through its diverse activation mechanisms and its involvement in multiple signal transduction pathways. This has made NLRP3 an appealing target for novel therapeutic strategies aimed at modulating inflammation in AP. Despite the growing interest in NLRP3 as a therapeutic target, there remains a notable gap in clinical research, with few clinical trials exploring the efficacy of NLRP3 inhibitors in AP. Results of several preclinical studies and animal models are promising and suggest that the use of NLRP3 inhibitors could result in reduced inflammation and improved patient outcomes in AP. Further research is urgently needed to assess their potential benefits, safety, and applicability in human patients and address the underlying inflammatory processes driving AP. Full article

The muskrat (Ondatra zibethicus) is an animal with special economic significance whose scented glands rapidly atrophy during the non-breeding season, but the mechanism of atrophy is not clear, with significant differences in apoptotic and pyroptotic signaling pathway expression according to transcriptome sequencing. During the non-breeding season, key apoptosis-related genes such as Tnfr1 (TNF Receptor Superfamily Member 1A), TRADD (TNFRSF1A Associated via Death Domain), FADD (Fas Associated via Death Domain), Casp-8 (Cysteine-aspartic proteases-8), and Bax (Bcl-associated X protein) were upregulated in the scented glands, while Bcl2 (B-cell lymphoma-2) expression was downregulated. In the classical pyroptosis pathway, the mRNA expression levels of key genes including Nlrp3 (the Nod-like receptor family pyrin domain-containing 3), ASC (the apoptosis-associated speck-like protein), Casp-1 (Cysteine-aspartic proteases-1), Gsdmd (Gasdermin D), and IL-1β (Interleukin 1 Beta) were higher during the non-breeding season, similar to the transcription level of Ripk1 (Receptor Interacting Serine/Threonine Kinase 1) in the non-canonical pyroptosis pathway, while TAK1 (transforming growth factor kinase) expression was downregulated in this latter pathway. TUNEL assays and immunofluorescence analysis indicated increased apoptosis and GSDMD and Caspase-8 protein levels during the non-breeding season. Indeed, the protein levels of GSDMD-N, Caspase-8 p43, and Caspase-8 p18 were significantly higher during the non-breeding season, while the GSDMD levels were significantly lower compared to the secretion season. These results suggest that apoptosis and pyroptosis play regulatory roles in scented gland atrophy and that there is an interplay between them during this process. Full article

Neuroplasticity and neuroinflammation are variables seen during recovery from traumatic brain injury (TBI), while biomarkers are useful in monitoring injury and guiding rehabilitation efforts. This systematic review examines how neuroinflammation affects neuroplasticity and recovery following TBI in animal models and humans. Studies were identified from an online search of the PubMed, Web of Science, and Embase databases without any search time range. This review has been registered on Open OSF (n) UDWQM. Recent studies highlight the critical role of biomarkers like serum amyloid A1 (SAA1) and Toll-like receptor 4 (TLR4) in predicting TBI patients’ injury severity and recovery outcomes, offering the potential for personalized treatment and improved neurorehabilitation strategies. Additionally, insights from animal studies reveal how neuroinflammation affects recovery, emphasizing targets such as NOD-like receptor family pyrin domain-containing 3 (NLRP3) and microglia for enhancing therapeutic interventions. This review emphasizes the central role of neuroinflammation in TBI, and its adverse impact on neuroplasticity and recovery, and suggests that targeted anti-inflammatory treatments and biomarker-based personalized approaches hold the key to improvement. Such approaches will need further development in future research by integrating neuromodulation and pharmacological interventions, along with biomarker validation, to optimize management in TBI. Full article