NLRP3 inflammasome activation in macrophages fuels sterile inflammation, which has been tied with metabolic reprogramming characterized by high glycolysis and low oxidative phosphorylation. The key enzymes in glycolysis and glycolysis‐related products can regulate and activate NLRP3 inflammasome. In turn, NLRP3 inflammasome is considered to affect glycolysis, as well. However, the exact mechanism remains ambiguous. On the basis of these findings, the focus of this review is mainly on the developments in our understanding of interaction between NLRP3 inflammasome activation and glycolysis in macrophages, and small molecule compounds that influence the activation of NLRP3 inflammasomes by regulating glycolysis in macrophages. The application of this interaction in the treatment of diseases is also discussed. This paper may yield valuable clues for development of novel therapeutic agent for NLRP3 inflammasome‐related diseases.

Objectives. We aimed to investigate the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on blood lipid levels in patients with high and very-high cardiovascular risk. Design. 14 trials (n = 52,586 patients) comparing treatment with or without PCSK9 inhibitors were retrieved from PubMed and Embase updated to 1st Jun 2021. The data quality of included studies was assessed by two independent researchers using the Cochrane systematic review method. All-cause mortality, cardiovascular mortality, and changes in serum low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), apolipoprotein B (ApoB), lipoprotein (a) (LP (a)), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein A1 (ApoA1) from baseline were analyzed using Rev Man 5.1.0 software. Results. Compared with treatments without PCSK9 inhibitor, addition of PCSK9 inhibitors (evolocumab and alirocumab) had obvious decreasing effects on the levels of LDL-C [MD = −46.86, 95% CI (−54.99 to −38.72), ], TC [MD = −31.92, 95% CI (−39.47 to −24.38), ], TG [MD = −8.13, 95% CI (−10.48 to −5.79), ], LP(a) [MD = −26.69, 95% CI (-27.93 to −25.44), ], non-HDL-C [MD = −42.86, 95% CI (−45.81 to −39.92), ], and ApoB [MD = −38.44, 95% CI (−42.23 to -34.65), ] in high CVD risk patients. Conversely, changes of HDL-C [MD = 6.27, CI (5.17 to 7.36), ] and ApoA1 [MD = 4.33, 95% CI (3.53 to 5.13), ] from baseline were significantly more in high cardiovascular disease risk patients who received PCSK9 inhibitors treatment. Conclusion. Addition of PCSK9 inhibitors to standard therapy resulted in definite improvement in blood lipid levels compared with therapies that did not include them.

Background. Alleviating mild cognitive impairment (MCI) is crucial to delay the progression of Alzheimers disease (AD). Jia-Wei-Kai-Xin-San (JWKXS) is applied for treating AD with MCI. However, the mechanism of JWKXS in the treatment of MCI is unclear. Thus, this study aimed to investigate the effect and mechanism of JWKXS in SAMP8 mice models of MCI. Methods. MCI models were established to examine learning and memory ability and explore the pathomechanisms in brain of SAMP8 mice at 4, 6, and 8 months. The mice were treated for 8 weeks and the effects of JWKXS on MCI were characterized through Morris water maze and HE/Nissls/immunohistochemical staining. Its mechanism was predicted by the combination of UPLC-Q-TOF/MS and system pharmacology analysis, further verified with SAMP8 mice, BV2 microglial cells, and PC12 cells. Results. It was found that 4-month-old SAMP8 mice exhibited MCI. Two months of JWKXS treatment improved the learning and memory ability, alleviated the hippocampal tissue and neuron damage. Through network pharmacology, four key signaling pathways were found to be involved in treatment of MCI by JWKXS, including TLR4/NF-κB pathway, NLRP3 inflammasome activation, and intrinsic and extrinsic apoptosis. In vitro and in vivo experiments demonstrated that JWKXS attenuated neuroinflammation by inhibiting microglia activation, suppressing TLR4/NF-κB and NLRP3 inflammasome pathways, and blocking the extrinsic and intrinsic apoptotic pathways leading to neuronal apoptosis suppression in the hippocampus. Conclusion. JWKXS treatment improved the learning and memory ability and conferred neuroprotective effects against MCI by inducing anti-inflammation and antiapoptosis. Limitations. The small sample size and short duration of the intervention limit in-depth investigation of the mechanisms. Future Prospects. This provides a direction for further clarification of the anti-AD mechanism, and provides certain data support for the formulation to move toward clinical practice.

Background Traditional Chinese herbal prescription BuYangHuanWu decoction (BHD) works well in treating atherosclerosis. However, the mechanism of BHD in atherosclerosis has not been fully elucidated. We aimed to determine whether BHD could alleviate atherosclerosis by altering the microbiome-associated metabolic changes in atherosclerotic mice. Methods An atherosclerotic model was induced in ApoE^−/−mice fed a high-fat diet (HFD), and BHD were administered by gavage for 12 weeks at 8.4g/kg/d and 16.8g/kg/d. Atherosclerotic plaque size, composition, serum lipid profile, as well as inflammatory cytokines were assessed. Mechanistically, metabolomic and micro biota profiling were analyzed using liquid chromatography mass spectrometry (LC-MS) and 16S rRNA gene sequencing, respectively. Further, intestinal microbiota and atherosclerosis-related metabolic parameters were correlated using Spearman analysis. Results Atherosclerotic mice treated with BHD showed a reduction in plaque area, aortic lumen occlusion, and lipid accumulation in the aortic root. 9 perturbed serum metabolites were significantly restored along with the relative abundance of micro biota at the family and genus levels, but not at the phylum level. Gut microbiota improvements were strongly negatively correlated with improved metabolite levels. Conclusions BHD treatment effectively slows the progression of atherosclerosis by regulating altered intestinal microbiota and perturbed metabolites. Detailed analysis of these interactions between intestinal microbes and metabolites affected by BHD will help in the development of new anti-atherosclerosis medications.