Simultaneous monitoring of seven antiepileptic drugs by dried blood spot and dried plasma spot sampling: method validation and clinical application of a LC-MS/MS-based technique.

Alternative blood sampling strategy can enhance the application of therapeutic drug monitoring (TDM), then improve precision therapy and medication compliance. In developing nations, alternative sampling strategy that allows self-sampling and room temperature transport is especially important. This study validates the use of dried blood spot (DBS) and dried plasma spot (DPS) sampling along with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for analyzing seven common antiepileptic drugs (AEDs) (phenytoin, lamotrigine, levetiracetam, topiramate, carbamazepine, oxcarbazepine and its active metabolite 10,11-dihydro-10-hydroxy carbamazepine) and evaluates their applicability to clinical practice. Following simple protein precipitation with acetonitrile, the AEDs were separated on a C18 column by gradient elution with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.65 mL/min. The method provided linear analysis over the tested concentration ranges, with a total run time of 7 min. Intra- and inter-assay precision for all quality controls were ≤12% with accuracies of 85.9%-113%. The average extraction efficiencies were 69.0%-92.4% for DBS and 65.9%-96.5% for DPS, and no significant matrix effects were observed. The AEDs were stable in all samples for seven days at room temprature and 40°C. There was good correlation between the dry and wet plasma concentrations with greater accuracy for DPS compared to DBS indicating that alternative sampling strategy using DBS and DPS are suitable for monitoring the concentrations of AEDs with satisfied performance and logistical advantages.

Discovery of a novel lead characterized by a stilbene-extended scaffold against sepsis as soluble epoxide hydrolase inhibitors.

Recently, some inhibitors of soluble epoxide hydrolase (sEH) showed limited potential in treating sepsis by increasing survival time, but they have unfortunately failed to improve survival rates. In this study, we initially identified a new hit 11D, belonging to a natural skeleton known as stilbene and having an IC50 of 644 nM on inhibiting murine sEH. Natural scaffold-based sEH inhibitors are paid less attention. A combination of structure-activity relationships (SARs)-guided structural optimization and computer-aided skeleton growth led to a highly effective lead compound 70P (IC50: 4.0 nM). The dose-response study indicated that 70P (at doses of 0.5-5 mg/kg, ip.) significantly increased survival rates and survival time by reducing the levels of the inflammatory factors TNF-α and IL-6 in the liver. Interestingly, 70P exhibited much higher accumulation in the liver than in plasma (AUC ratio: 175). In addition, 70P exhibits equal IC50 value (1.5 nM) on inhibiting human sEH as EC5026 (1.7 nM). In conclusion, the natural scaffold-extended sEH inhibitor 70P has the potential to become a new promising lead for addressing the unmet medical need in sepsis treatment, which highlighted the importance of natural skeleton in developing sEH inhibitors.

Determination of Vitamin K1, MK-4, MK-7, and D Levels in Human Serum of Postmenopausal Osteoporosis Women Based on High Stability LC-MS/MS: MK-7 May Be a New Marker of Bone Metabolism.

INTRODUCTION: Vitamin K (VK) as well as vitamin D (VD) plays an important role in osteoporosis. Vitamin K1 (VK1), vitamin K2 (VK2, menaquinone-4 (MK-4), and menaquinone-7 (MK-7)) are significant for the metabolism of skeletal muscle. 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 (25(OH)D2 and 25(OH)D3) reflect circulating VD levels. More sensitive measurements remain to be developed. In the present study, a new high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of VK1, VK2 (MK-4 and MK-7), as well as 25(OH)D2 and 25(OH)D3 levels in human serum. METHODS: We developed a simple LC-MS/MS method for the determination of VK1, MK-4, MK-7, 25(OH)D2, and 25(OH)D3 levels in human serum and validated the method in a study cohort of 200 patients divided into the premenopausal women group and postmenopausal osteoporosis patient group. RESULTS: The overall precision (coefficient of variation) ranged from 2.66 to 10.11% in the specified working range (0.05-5 ng/mL) for VK1, MK-4, and MK-7. Serum VK1, MK-4, and MK-7 levels in postmenopausal women with osteoporosis were 1.187 ± 0.094 ng/mL, 0.058 ± 0.009 ng/mL, and 0.885 ± 0.064 ng/mL, respectively (mean ± standard deviation). Serum VK1, MK-4, and MK-7 levels in premenopausal women were 1.143 ± 0.103 ng/mL, 0.028 ± 0.003 ng/mL, and 1.553 ± 0.226 ng/mL, respectively. Serum 25(OH)D2 and 25(OH)D3 levels in postmenopausal women with osteoporosis were 0.757 ± 0.056 ng/mL and 11.72 ± 0.632 ng/mL, respectively. Serum 25(OH)D2 and 25(OH)D3 levels in premenopausal were 1.793 ± 0.575 ng/mL and 12.42 ± 1.069 ng/mL, respectively. CONCLUSION: A new LC-MS/MS method for determination of serum VK and VD levels was evaluated and validated. MK-7 in plasma decreased earlier than VD in postmenopausal osteoporosis patients. MK-7 status is significantly associated with osteoporosis and could be considered a predictable biomarker in the diagnosis of osteoporosis in postmenopausal women.

Advances in traditional Chinese medicine as adjuvant therapy for diabetic foot.

Diabetes mellitus (DM) is a complex disease that often causes multiple systemic complications that have become a major international public health problem. Diabetic foot (DF) is one of the severe and frequent chronic complications of DM due to vascular lesions and neuropathy. DF ulcers (DFU) affect approximately 15% of people with DM and are the leading cause of death and disability. The prevalence and recurrence of DF are worrisome, and morbidity and mortality are also on the rise, which poses a substantial socioeconomic burden. Treating DF is difficult for clinicians and requires multidisciplinary cooperation, combining local and systemic therapy to reduce amputation and case-fatality rates. Traditional Chinese Medicine (TCM) has received extensive attention due to noticeable therapeutic effects and few adverse reactions. In recent years, research on DF treatment by TCM has been increasing, and further progress has been made. TCM includes oral medication, injectable preparations, and adjuvant therapy. This article reviews the relevant research on TCM-related adjuvant therapy for DF. We describe current progress in TCM in terms of external application, acupuncture, massage, acupoint injection, foot bath, fumigation, and moxibustion, as well as the mechanisms involved.

Effect of Aerobic Exercise on Liver Tissue in Rats with NAFLD.

Objective: To observe the improvement effect of aerobic exercise on liver tissue of rats with NAFLD, explore whether it can reduce NAFLD symptoms without drug dependence, and provide certain data support for the relief of NAFLD by aerobic exercise. Methods: 40 healthful male SD rats have been divided into ordinary diet and high-fat diet. To observe whether the molding is forming after 6 weeks, then divide the rats into control (C), model (M), and exercise (E) group. E group received 8-week aerobic exercise intervention. Serum and liver samples were taken and analyzed after the last intervention. Results: The morphological of hepatocytes between C and M group becomes different, and the accumulation of fat and inflammatory cells was significant, suggesting that NAFLD symptoms appeared, that is, the model was successfully established. Compared with M group, the morphology of rats in E group was improved in varying degrees. The quantity of ALT, AST, and MDA of rats in M group is increased, and the SOD activity is significantly reduced (P < 0.01). However, aerobic exercise intervention changed those result (P < 0.01). Conclusions: Aerobic exercise can relieve oxidative stress damage, lipid peroxidation levels, and chronic inflammatory status in rats with NAFLD, which can reduce NAFLD symptoms without drug dependence, and is expected to become a means of NAFLD treatment.

Effect of Aerobic Exercise on Lipid Metabolism in Rats With NAFLD.

This work aimed to study the intervention effect of exercise on lipid metabolism in NAFLD rats, provide a more scientific experimental basis for exploring and improving the theoretical system of exercise intervention in NAFLD, and further provide a theoretical research basis for clinical treatment of NAFLD. Forty healthy male Sprague Dawley rats were randomly divided into a blank control group (BC,14) and a model group (MO, 26). After 6°weeks of modeling, the MO group was randomly divided into the model control group (MC, 12) and the aerobic exercise group (AE, 12). Platform running intervention in group E was conducted at a slope of 0°, a speed of 15 m/min, 1 h/time, once a day, six times a week, and a day of rest, for 8°weeks in total. After the intervention, the liver tissues of rats were taken for pathological sections, and serum was taken and analyzed for TC, TG, LDL-C, HDL-C, and FFA levels. Under the light microscope, the liver tissue structure of rats in the BC group was complete and clear, the structure of liver lobules was clear and normal, the volume of hepatocytes was uniform, the nucleus was in the middle, and the cytoplasm was red-stained, and no steatosis of hepatocytes was found. The liver of rats in the MC group showed diffuse fatty lesions, disordered structure of hepatic lobules, disordered arrangement of hepatic cords, different sizes of hepatocytes, loose cytoplasm, and diffuse lipid droplets of different sizes in the cytoplasm. The accumulation of liver lipid droplets in the AE group was improved compared with the MC group, the number of fat vacuoles in hepatocytes was significantly reduced, and the degree of liver lipid deposition was reduced. Compared with the BC group, the content of TC, TG, LDL-C, and FFA in the serum of the MC group increased significantly (p < 0.01), and the content of HDL-C decreased significantly (p < 0.01). Compared with the MC group, the content of TC, TG, LDL-C, and FFA in the serum of the AE group decreased significantly (p < 0.01/p < 0.05), and the content of HDL-C increased significantly (p < 0.01). Therefore, moderate-intensity aerobic exercise has an intervention effect on lipid metabolism in NAFLD rats, which can be used as one of the means to treat NAFLD.

A Wearable Gait Analysis and Recognition Method for Parkinson's Disease Based on Error State Kalman Filter.

For the purpose of quantitative analysis, this paper proposes a wearable gait analysis method for Parkinson's disease (PD) to evaluates the motor ability. The error state Kalman filter (ESKF) is used for attitude estimation, and the gait parameters are modified by phase segmentation and zero velocity update (ZUPT) algorithm. In addition, this study uses gait parameters as classifier features to recognize abnormal gait, and compares the recognition effect with statistical features. The effect of our gait system is verified by comparison with the OptiTrack system, and the mean absolute error (MAE) of step length and foot clearance are 2.52 ±3.61 cm and 0.96 ±1.24 cm respectively. Forty Parkinson's patients and forty age-matched healthy people are recruited for gait comparison, the analysis results showed significant differences between the two groups. The abnormal gait recognition results show that gait features have stronger generalization ability than statistical features in leave-one-subject-out (LOSO) validation. The method proposed in this study can be applied to the gait analysis and objective evaluation of PD.

Highly unstable heterogeneous representations in VIP interneurons of the anterior cingulate cortex.

A hallmark of the anterior cingulate cortex (ACC) is its functional heterogeneity. Functional and imaging studies revealed its importance in the encoding of anxiety-related and social stimuli, but it is unknown how microcircuits within the ACC encode these distinct stimuli. One type of inhibitory interneuron, which is positive for vasoactive intestinal peptide (VIP), is known to modulate the activity of pyramidal cells in local microcircuits, but it is unknown whether VIP cells in the ACC (VIPACC) are engaged by particular contexts or stimuli. Additionally, recent studies demonstrated that neuronal representations in other cortical areas can change over time at the level of the individual neuron. However, it is not known whether stimulus representations in the ACC remain stable over time. Using in vivo Ca2+ imaging and miniscopes in freely behaving mice to monitor neuronal activity with cellular resolution, we identified individual VIPACC that preferentially activated to distinct stimuli across diverse tasks. Importantly, although the population-level activity of the VIPACC remained stable across trials, the stimulus-selectivity of individual interneurons changed rapidly. These findings demonstrate marked functional heterogeneity and instability within interneuron populations in the ACC. This work contributes to our understanding of how the cortex encodes information across diverse contexts and provides insight into the complexity of neural processes involved in anxiety and social behavior.

Study on the Pharmacokinetic Profiles of Three Ingredients in Qilong Capsules and Their Potential Interactions in Rats by LC-MS/MS.

Qilong capsule (QLC) is a well-known Traditional Chinese Medicine, and it has a long history for the treatment of ischemic stroke. Its major ingredients are saponins, such as paeoniflorin, amygdalin and calycosin-7-glucoside, contributing to vasodilation function. In this study, a simple, rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry method was developed to determine three bioactive ingredients in rat plasma after oral administration of QLC. A simple acetonitrile precipitation method was introduced during the sample preparation. Chromatographic separation was performed on a Shiseido CAPCELL PAC MGIII-C18 column using a gradient elution with acetonitrile and water (0.1% formic acid) as a mobile phase, and the chromatographic separation was 5 min. The methodological evaluation showed that this method had a high sensitivity (the lower limit of quantification was 1 ng/mL for calycosin-7-glucoside, 5 ng/mL for paeoniflorin, 5 ng/mL for amygdalin), satisfactory accuracy (relative error ≤ ±15%) and precision (relative standard deviation ≤15%). Then, the analytical method was applied to the pharmacokinetic study in rats following oral administration of the extracts in QLC. Meanwhile, the pharmacokinetic parameters of complex system in QLC were analyzed and the potential interaction between ingredients was explored. The present quantification method and pharmacokinetic study will provide a meaningful reference for the formulas research of QLC in the treatment of ischemic stroke.

The predictive value of preoperative luteinizing hormone to follicle stimulating hormone ratio for ovulation abnormalities recovery after laparoscopic sleeve gastrectomy: A prospective cohort study.

Introduction: Obesity-related ovulation abnormalities (OA) affect fertility. LSG is the most frequent bariatric operation. However, no research has identified a reliable indicator for predicting OA recovery after LSG. The purpose of this research was to examine the prognostic usefulness of preoperative the luteinizing hormone (LH) to follicle-stimulating hormone (FSH) ratio (LFR). Methods: Our department conducted a prospective study from 2016 to 2021. Venous blood was typically tested 3 days before surgery to get the preoperative LFR. Descriptive data, preoperative and postoperative variables were also collected. Binary logistic regression related preoperative LFR with OA recovery. The receiver operating characteristic (ROC) curve evulated preoperative LFR's predictive capability. Results: A total of 157 women with a complete follow-up of one year were included. LFR was the only factor linked with OA (P < 0.001). AUC (area under the ROC curve) = 0.915, cutoff = 1.782, sensitivity = 0.93, and specificity = 0.82. Discussion: Overall, LSG has a favorable surgical result, with a %TWL of 66.082 ± 12.012 at 12 months postoperatively. Preoperative sexual hormone levels, as expressed by LFR, has the potential to predict the fate of OA following LSG at one year post-operatively.

A developed HPLC-MS/MS method to quantitate 5 steriod hormones in clinical human serum by using PBS as the surrogate matrix.

Steroid hormones play an essential role in regulating physiological and reproductive development throughout the lifetime of an individual. One of the difficulties in determining endogenous substances is the lack of a blank matrix. Especially when the level of analytes is lower than the level in the so-called blank matrix. In the present study, an optimized HPLC-MS/MS method was developed and validated to quantify androstenedione (ASD), testosterone (Ts), dehydroepiandrosterone (DHEA), 5α-dihydrotestosterone (DHT), and progesterone (P) in serum samples from healthy people using PBS (pH = 7.4) as the blank surrogate matrix. Simultaneously, the method investigated the characteristics of NaCl, bull serum albumin, pure water as surrogate matrices for the analysis of steroid hormones. The data showed that the matrix effects of ASD, Ts, DHEA, DHT, and P in the same groups were not significantly different between PBS and twice charcoal-stripped serum (CS2S) as a blank surrogate matrix. Furthermore, the LLOQ using PBS as the blank matrix was up to 0.005 ng/mL for ASD, Ts, and P and 0.05 ng/mL for DHEA and DHT. The reference ranges of concentration (CPBS) of 5 steroid hormones were provided. Compared to the concentration with CS2S (CCSS) as the blank surrogate matrix, the relative biases (RBs) of Ts, DHT, P, and DHEA were finally stabilized at approximately -0.7%, -15%, -1.2%, and 9.2%, respectively. The results suggest that, in the cases of special required, the developed HPLC-MS/MS method can be used to determine the absolute concentration of 5 hormones in biological samples with PBS as the blank surrogate matrix.

Development of a novel tandem mass spectrometry method for the quantification of eszopiclone without interference from 2-amino-5-chloropyridine and application in a pharmacokinetic study of rat.

Eszopiclone (E-ZOP), a strictly controlled psychoactive drug, must be accurately quantified in biological matrices. However, because of its rapid degradation and transformation into 2-amino-5-chloropyridine (ACP) during specimen preparation, the concentration of E-ZOP in biological matrices is likely underestimated. In this study, a sensitive and simple high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the accurate determination of the initial concentration of E-ZOP in rat plasma was developed and validated. ACP was monitored simultaneously throughout the method validation process to ensure that it was not produced via E-ZOP hydrolysis. E-ZOP and structurally similar metabolites were stabilized in rat plasma by controlling the pH at 4.2 using a modified phosphate buffer solution (PBS) with acetic acid. Using this method, E-ZOP, ACP and the internal standard (IS), venlafaxine, were extracted from rat plasma via a simple protein precipitation and separated on a C18 column using methanol, 5 mM ammonium acetate, and 0.1 % acetic acid as the isocratic mobile phase. The validated method covered a working range from 0.1-50 ng/mL for E-ZOP, and the lower limit of detection (LLOD) for ACP was 0.2 ng/mL. In conclusion, an accurate, sensitive, and simple HPLC-MS/MS method for E-ZOP quantification was developed and successfully applied to a preclinical pharmacokinetics (PK) study in rats. The toxic product APC was effectively monitored. The HPLC-MS/MS method is a stable and sensitive quantitative method for the determination of E-ZOP in biological matrices.

Regulations of Glycolytic Activities on Macrophages Functions in Tumor and Infectious Inflammation.

Macrophages differentiated into a classically activated (M1) or alternatively activated phenotype (M2) in infection and tumor, but the precise effects of glycolysis and oxidative phosphorylation (OXPHOS) metabolic pathway remain unclear. Herein, the effects of glycolysis or OXPHOS on macrophage polarizations were investigated using a pharmacological approach in mice. 2-Deoxy-D-glucose (2-DG) treatments, which blocks the key enzyme hexokinase of glycolysis, efficiently inhibits a specific switch to M1 lineage, decreasing the secretion of pro-inflammatory cytokines and expressions of co-stimulatory molecules associated with relieving infectious inflammation in vitro and in vivo. Glycolytic activation through the hypoxia-inducible factor-1α (HIF-1α) pathway was required for differentiation to the M1 phenotype, which conferred protection against infection. Dimethyl malonate (DMM) treatment, which blocks the key element succinate of OXPHOS, efficiently inhibits a specific switch to M2 lineage when macrophages receiving M2 stimulation, decreasing the secretion of anti-inflammatory cytokine and CD206 expressions. Mitochondrial dynamic alterations including mitochondrial mass, mitochondrial membrane potential (Dym) and ROS productions were critically for differentiation to the M2 phenotype, which conferred protection against anti-tumor immunity. Glycolysis is also required for macrophage M2 differentiation. Thus, these data provide a basis for a comprehensively understanding the role of glycolysis and OXPHOS in macrophage differentiation during anti-infection and anti-tumor inflammation.

Glucocorticoids Promote the Onset of Acute Experimental Colitis and Cancer by Upregulating mTOR Signaling in Intestinal Epithelial Cells.

The therapeutic effects of glucocorticoids on colitis and colitis-associated cancer are unclear. In this study, we investigated the therapeutic roles of glucocorticoids in acute experimental ulcerative colitis and colitis-associated cancer in mice and their immunoregulatory mechanisms. Murine acute ulcerative colitis was induced by dextran sulfate sodium (DSS) and treated with dexamethasone (Dex) at different doses. Dex significantly exacerbated the onset and severity of DSS-induced colitis and potentiated mucosal inflammatory macrophage and neutrophil infiltration, as well as cytokine production. Furthermore, under inflammatory conditions, the expression of the glucocorticoid receptor (GR) did not change significantly, while mammalian target of rapamycin (mTOR) signaling was higher in colonic epithelial cells than in colonic immune cells. The deletion of mTOR in intestinal epithelial cells, but not that in myeloid immune cells, in mice significantly ameliorated the severe course of colitis caused by Dex, including weight loss, clinical score, colon length, pathological damage, inflammatory cell infiltration and pro-inflammatory cytokine production. These data suggest that mTOR signaling in intestinal epithelial cells, mainly mTORC1, plays a critical role in the Dex-induced exacerbation of acute colitis and colitis-associated cancer. Thus, these pieces of evidence indicate that glucocorticoid-induced mTOR signaling in epithelial cells is required in the early stages of acute ulcerative colitis by modulating the dynamics of innate immune cell recruitment and activation.

Determination of the in vitro metabolic stability and metabolites of the anticancer derivative riccardin D-N in human and mouse hepatic S9 fractions using HPLC-Q-LIT-MS.

Riccardin D-N (RD-N) is an aminomethylated derivative of the macrocyclic bisbibenzyl compound riccardin D (RD), which has shown stronger activity against cancer cells than RD. However, there has been no research on the metabolism of RD-N. The present study aimed to characterize the in vitro metabolism and metabolic stability of RD-N after incubation with mouse and human hepatic S9 fractions using high performance liquid chromatography-hybrid triple quadrupole/linear ion trap mass spectrometry (HPLC-Q-LIT-MS). Multiple ion monitoring (MIM) and multiple reaction monitoring (MRM)-information dependent acquisition-enhanced product ion (MIM/MRM-IDA-EPI) scans were used to identify the metabolites formed. MRM scans were also used to quantify the changes in the amount of RD-N and to semi-quantify the main metabolites. Twenty-eight metabolic products were detected and 25 structures were predicted. Hydroxylation, dehydrogenation, glucuronidation, and methylation were proposed to be the principle metabolic pathways in the in vitro incubation with human and mouse hepatic S9 fractions. There were differences in the number and abundance of RD-N metabolites between the human and mouse hepatic S9 fractions. RD-N was shown to have good metabolic stability. After 2 h of incubation, 44% of the original RD-N remained in the human hepatic S9 fraction compared with 22% in the mouse. The major metabolites of RD-N, M4, M8, M20 and M21, were monitored semi-quantitatively using the typical transitions. Finally, HPLC-Q-LIT-MS was used for the identification and quantitation of the metabolites of R D-N, which is a simple and efficient method to rapidly screen potential drug candidates.

Metabolic reprogramming of macrophages during infections and cancer.

In response to different microenvironmental stimuli, macrophages are polarized into two populations, M1 macrophages which are classically activated by interferon (IFN)-γ with lipopolysaccharides (LPSs) and M2 macrophages which are alternatively activated by interleukin-4 (IL-4), to perform specific roles in innate immune responses. Accordingly, macrophages occupy distinct metabolic profiles, regulated by orchestrated factors and signaling pathways, including the PI3K-AKT, HIF, c-Myc, AMPK, and PPARs pathways. These factors and pathways play pivotal roles not only in metabolic regulation but also in macrophage polarization. After activation, classically activated M1 macrophages and alternatively activated M2 macrophages display distinct patterns in glucose, lipid, amino acid and iron metabolism. Here, we summarized recently discovered metabolism-related inflammatory signaling factors, along with reprogrammed metabolism, after the activation of macrophages under conditions related to immunity and cancer. Additionally, macrophage regulatory roles in infectious diseases, cancer progression and anti-cancer immunotherapy are discussed in terms of metabolic profiles, providing insight into the prevention and treatment of immune-associated diseases.

Data mean and ratio of absorbance to concentration methods: A novel optimization strategy for near infrared spectroscopy modeling.

For the modeling of near infrared spectroscopy (NIRS), the accuracy of the basic data, the stability of the spectra and the optimality of variables selection method were the important factors. In this paper, a novel optimization strategy for NIRS modeling was proposed, which was formed by data mean and ratio of absorbance to concentration (RATC) methods. The data mean method was aim to obtain accurate basic data and stable spectra, the RATC method was aim to select the optimal variables and compared with other variables selection methods (FiPLS, BiPLS, CC, UVE). The experimental subject was raw human plasma, with this novel optimization strategy, the predictive capability of NIRS model of its total protein (TP) content had been improved. At the same time, the public NIRS testing data (water, protein, oil, starch of corn and octane of gasoline) were used to verify the proposed variables selection method, and the predictive capability of these models of different parameters were also improved. To some extent, the optimization strategy of NIRS modeling provided theoretical supports for the development of protein content analyzer of NIRS and the quick determination of parameters of biologics and other materials.

Metabolic regulation of inflammasomes in inflammation.

Inflammasome activation and subsequent inflammatory cytokine secretion are essential for innate immune defence against multiple stimuli and are regarded as a link to adaptive immune responses. Dysfunction of inflammasome activation has been discovered at the onset or progression of infectious diseases, autoimmune diseases and cancer, all of which are also associated with metabolic factors. Furthermore, many studies concerning the metabolic regulation of inflammasome activation have emerged in recent years, especially regarding the activity of the NLRP3 inflammasome under metabolic reprogramming. In this review, we discuss the molecular mechanisms of the interactions between metabolic pathways and inflammasome activation, which exerts further important effects on various diseases.