Laboratory Preparation for Digital Medicine in Healthcare 4.0: An Investigation Into the Awareness and Applications of Big Data and Artificial Intelligence.

Background: Healthcare 4.0. refers to the integration of advanced technologies, such as artificial intelligence (AI) and big data analysis, into the healthcare sector. Recognizing the impact of Healthcare 4.0 technologies in laboratory medicine (LM), we seek to assess the overall awareness and implementation of Healthcare 4.0 among members of the Korean Society for Laboratory Medicine (KSLM). Methods: A web-based survey was conducted using an anonymous questionnaire. The survey comprised 36 questions covering demographic information (seven questions), big data (10 questions), and AI (19 questions). Results: In total, 182 (17.9%) of 1,017 KSLM members participated in the survey. Thirty-two percent of respondents considered AI to be the most important technology in LM in the era of Healthcare 4.0, closely followed by 31% who favored big data. Approximately 80% of respondents were familiar with big data but had not conducted research using it, and 71% were willing to participate in future big data research conducted by the KSLM. Respondents viewed AI as the most valuable tool in molecular genetics within various divisions. More than half of the respondents were open to the notion of using AI as assistance rather than a complete replacement for their roles. Conclusions: This survey highlighted KSLM members' awareness of the potential applications and implications of big data and AI. We emphasize the complexity of AI integration in healthcare, citing technical and ethical challenges leading to diverse opinions on its impact on employment and training. This highlights the need for a holistic approach to adopting new technologies.

Involvement of the anterior insula and frontal operculum during wh-question comprehension of wh-in-situ Korean language.

In this research, we employed functional magnetic resonance imaging (fMRI) to examine the neurological basis for understanding wh-questions in wh-in-situ languages such as Korean, where wh-elements maintain their original positions instead of moving explicitly within the sentence. Our hypothesis centered on the role of the salience and attention network in comprehending wh-questions in wh-in-situ languages, such as the discernment of wh-elements, the demarcation between interrogative types, and the allocation of cognitive resources towards essential constituents vis-à-vis subordinate elements in order to capture the speaker's communicative intent. We explored subject and object wh-questions and scrambled wh-questions, contrasting them with yes/no questions in Korean. Increased activation was observed in the left anterior insula and bilateral frontal operculum, irrespective of the wh-position or scrambling of wh-element. These results suggest the interaction between the salience and attentional system and the syntactic linguistic system, particularly the left anterior insula and bilateral frontal operculum, in comprehending wh-questions in wh-in-situ languages.

Prognostic Significance of Clinical Factors Including BRCA Mutation in Epithelial Ovarian, Peritoneal, Fallopian Tube Cancer.

BACKGROUND/AIM: We analyzed the survival outcomes of patients with epithelial ovarian, peritoneal, or fallopian tube cancer with BRCA1/2 mutations and the clinical factors associated with the prognosis of these cancers. PATIENTS AND METHODS: We included patients who had been diagnosed with and treated for epithelial ovarian, peritoneal, or fallopian tube cancer and had undergone germline BRCA testing in six hospitals between January 2012 and December 2019. RESULTS: Of the 378 identified patients, 76 (20.1%) carried a BRCA1/2 mutation. Progression-free survival (PFS) and overall survival (OS) did not differ between patients with and without BRCA1/2 mutation. Multivariate analysis for 18 months after the primary treatment showed higher PFS in the BRCA1/2 mutation group (p=0.024). Subgroup analysis in patients with high-grade serous carcinoma showed that BRCA1/2 mutation was an independent favorable prognostic factor for PFS (p=0.035). Subgroup analysis of patients with stage III or IV disease demonstrated an independent gain in PFS in patients with BRCA1/2 mutation (p=0.015). Neoadjuvant chemotherapy as a primary treatment was related to poor PFS (p<0.001) and reduced OS (p=0.005). CONCLUSION: Having a germline BRCA1/2 mutation improved short-term PFS in patients with epithelial ovarian, peritoneal, or fallopian tube cancer. Elevated initial CA125 level and primary neoadjuvant chemotherapy were related to poor prognosis.

Extratendinous migration of calcific tendinitis of the rotator cuff: imaging findings and clinical characteristics with temporal changes.

PURPOSE: The aim of this study was to analyze the imaging findings and clinical characteristics of extratendinous migration of calcific tendinitis of the shoulder with temporal changes. METHODS: Seventy-six patients with extratendinous calcific tendinitis of the shoulder diagnosed by ultrasonography (US) or magnetic resonance imaging (MRI) were enrolled in this retrospective study. Clinical symptoms and imaging findings (on radiography, US, and MRI) of extratendinous calcific tendinitis during an acute painful attack were analyzed. Temporal changes were analyzed in 28 patients before an acute attack and 40 patients after an acute attack. For comparison, 65 patients with intratendinous calcific tendinitis were included. RESULTS: Patients with extratendinous calcific tendinitis had a significantly higher average visual analogue scale (VAS) score (8.8±1.6) than the intratendinous group (6.4±2.2) (P<0.001). The fragmented type (80.5%) was the most common shape on US; sonographic black hole appearance (14.6%) and echogenic fluid (9.8%) were characteristic findings of intrabursal calcifications. In 28 patients with previous radiographs, radiographic type III (78.6%) was dominant and the location of calcific deposits changed (82.1%) during the acute painful attack, which was also perceivable in 12 patients with previous US or MRI. In follow-up radiographs of 40 patients, calcifications shrunk by more than 50% or became invisible in 82.5% of patients, with symptom improvement (VAS score, 8.9±1.5 to 1.9±1.2). Follow-up US and MRI of 16 patients also showed decreased size (56.3%) or disappearance (43.7%) of calcific deposits. CONCLUSION: Extratendinous calcific tendinitis has distinctive imaging features, the temporal changes of which correlate well with clinical symptoms.

Highly Stereoselective Asymmetric Total Synthesis of (-)-Jimenezin via Sequential Intramolecular Amide Enolate Alkylation.

A highly stereoselective asymmetric total synthesis of (-)-jimenezin (1), a potent anticancer acetogenin, was efficiently completed with the key feature being a sequential intramolecular amide enolate alkylation (IAEA). Our investigation to probe the origin of the complete stereoselectivity in the second IAEA step to form the conformationally flexible tetrahydrofuran with perfect stereocontrol identified the presence of the oxygen atom in the adjacent tetrahydropyran ring to be crucial.

Synthesis of Halogenated 1,5-Diarylimidazoles and Their Inhibitory Effects on LPS-Induced PGE2 Production in RAW 264.7 Cells.

A series of halogenated 1,5-diarylimidazole compounds were synthesized and their inhibitory effects on LPS-induced PGE2 production in RAW 264.7 cells were evaluated. A wide variety of 2,4-, 4-, and 2-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles were synthesized for SAR study via two different pathways. Overall, 4-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles, regardless of the species of halogen, exhibited very strong inhibitory activities of PGE2 production. Among them, 4-chloro-5-(4-methoxyphenyl)-1-(4-methylsulfonylphenyl)imidazole (3, IC50 3.3 nM ± 2.93), and 4-chloro-5-(4-chlorophenyl)-1-(4-methylsulfonylphenyl)imidazole (13, IC50 5.3 nM ± 0.23) showed the best results.

Internal Quality Control Data of Urine Reagent Strip Tests and Derivation of Control Rules Based on Sigma Metrics.

BACKGROUND: Urine reagent strip test (URST) results are semi-quantitative; therefore, the precision of URSTs is evaluated as the proportion of categorical results from repeated measurements of a sample that are concordant with an expected result. However, URSTs have quantitative readout values before ordinal results challenging statistical monitoring for internal quality control (IQC) with control rules. This study aimed to determine the sigma metric of URSTs and derive appropriate control rules for IQC. METHODS: The URiSCAN Super Plus fully automated urine analyzer (YD Diagnostics, Yongin, Korea) was used for URSTs. Change in reflectance rate (change %R) data from IQC for URSTs performed between November 2018 and May 2020 were analyzed. Red blood cells, bilirubin, urobilinogen, ketones, protein, glucose, leukocytes, and pH were measured from 2-3 levels of control materials. The total allowable error (TEa) for a grade was the difference in midpoints of a predefined change %R range between two adjacent grades. The sigma metric was calculated as TEa/SD. Sigma metric-based control rules were determined with Westgard EZ Rules 3 software (Westgard QC, Madison, WI, USA). RESULTS: Seven out of the eight analytes had a sigma metric >4 in the control materials with a negative grade (-), which were closer to the cut-offs. Corresponding control rules ranged from 12.5s to 13.5s. CONCLUSIONS: Although the URST is a semi-quantitative test, statistical IQC can be performed using the readout values. According to the sigma metric, control rules recommended for URST IQC in routine clinical practice are 12.5s to 13.5s.

Interruption of Helicobacter pylori-Induced NLRP3 Inflammasome Activation by Chalcone Derivatives.

Helicobacter pylori causes chronic gastritis through cag pathogenicity island (cagPAI), vacuolating cytotoxin A (VacA), lipopolysaccharides (LPS), and flagellin as pathogen-related molecular patterns (PAMPs), which, in combination with the pattern recognition receptors (PRRs) of host cells promotes the expression and secretion of inflammation-causing cytokines and activates innate immune responses such as inflammasomes. To identify useful compounds against H. pylori-associated gastric disorders, the effect of chalcone derivatives to activate the nucleotide-binding oligomerization domain (NOD)-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome was examined in an H. pylori-infected human monocytic THP-1 cell line in this study. Among the five synthetic structurally-related chalcone derivatives examined, 2'-hydroxy-4',6'-dimethoxychalcone (8) and 2'-hydroxy-3,4,5- trimethoxychalcone (12) strongly blocked the NLRP3 inflammasome in H. pylori-infected THP-1 cells. At 10 µM, these compounds inhibited the production of active IL-1ß, IL-18, and caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) oligomerization, but did not affect the expression levels of NLRP3, ASC, and pro-caspase-1. The interruption of NLRP3 inflammasome activation by these compounds was found to be mediated via the inhibition of the interleukin-1 receptor-associated kinase 4 (IRAK4)/IκBα/NF-κB signaling pathway. These compounds also inhibited caspase-4 production associated with non-canonical NLRP3 inflammasome activation. These results show for the first time that certain chalcones could interrupt the activation of the NLRP3 inflammasome in H. pylori-infected THP-1 cells. Therefore, these chalcones may be helpful in alleviating H. pylori-related inflammatory disorders including chronic gastritis.

Low serum T3 levels are associated with false-positive results when using the risk of ovarian malignancy algorithm (ROMA) in women with benign ovarian disease.

OBJECTIVE: We investigated factors that could cause false-positive results when using the risk of ovarian malignancy algorithm (ROMA) for assessing ovarian cancer risk. MATERIALS AND METHODS: ROMA scores were calculated from patients followed surgery to remove a pelvic mass. We compared a false-positive group with a true-negative group of ROMA scores. RESULTS: We analyzed 324 patients using medical records. There were 22 with an epithelial ovarian cancer (EOC), 15 with a borderline ovarian tumor, and 287 with benign disease. Twenty-nine (10.1%) of the patients with benign disease showed high-risk ROMA score (false positive) and 13/37 (35%) patients with EOC, or borderline ovarian tumor showed low ROMA scores (false negatives). The median serum triiodothyronine (T3) level of the false-positive ROMA group in patients with benign disease was lower than in the true-negative ROMA group (p < 0.001) and the estimated glomerular filtration rate (eGFR) was also lower (p = 0.001) in the false-positive ROMA group. Median serum T3 levels in the true-positive ROMA group among patients with EOC, or borderline ovarian tumor were lower than in the false-negative ROMA group (p = 0.043). CONCLUSION: Median serum T3 level and eGFR in the false-positive ROMA group in patients with benign ovarian disease were lower than in the true-negative group.

Synthesis, in vitro evaluation, and computational simulations studies of 1,2,3-triazole analogues as DPP-4 inhibitors.

Novel 1,2,3-triazole analogues (S7 ~ S10) were synthesized and evaluated for their inhibitory activity against hDPP-4. All the 1,2,3-triazole analogues exhibited moderate in vitro hDPP-4 inhibitory activities (265 ~ 780 nM). These results are somewhat less potent compared to those of known 1,2,3-triazole analogues (S1 ~ S6, 14 ~ 254 nM). S2 and S3 manifested excellent potency against hDPP-4 with IC50s of 28 and 14 nM, respectively. The role of the 1,2,3-triazole moiety in binding the molecule to the target was investigated using combined 10 1,2,3-triazole analogues (S1 ~ S10). Molecular dynamics (MD) simulations following the aforementioned docking phase were performed to elucidate potential binding modes of sitagliptin's 1,2,3-triazole analogues in hDPP-4, with the use of a cocrystal structure of hDPP-4 with sitagliptin (PDB ID: 1X70). Docking and MD simulations of the complexes of hDPP-4 with sitagliptin, S2 and S3 suggest that Glu205, Glu206, Tyr662, and Tyr666 would be the key amino acid residues for the binding of the molecules with the receptor. Especially, S2 and S3 showed additional strong π-π interaction between Phe357 and 1,2,3-triazole. Same strong π-π interaction is also observed between Phe357 and the 1,2,4-triazole ring of sitagliptin. Furthermore, additional interactions with Tyr547, Cys551, and especially Arg358 would enhance the binding affinity of the compounds for the pocket of the enzyme. In overall, in vitro hDPP-4 inhibitory activities of synthetic 1,2,3-triazole analogues were well matched with results of computational simulations studies.

Cross-Metathesis of Methallyl Halides: Concise Enantioselective Formal Total Synthesis of (-)-Presphaerene.

The cross-metathesis (CM) of methallyl halides catalyzed using four different ruthenium-based complexes-Grubbs catalyst, Grubbs second-generation catalyst, Hoveyda-Grubbs second-generation catalyst, and Stewart-Grubbs catalyst-was investigated. When methallyl chloride or bromide was reacted with a model substrate containing a benzyl ether group, the Grubbs catalyst, and Grubbs second-generation catalyst did not promote the reaction well. However, the Hoveyda-Grubbs second-generation catalyst and Stewart-Grubbs catalyst afforded the corresponding products in moderate to good yield with moderate E/Z selectivity. Accordingly, several functionalized methallyl halides were prepared by CM. Various functional groups were well-tolerated in this system when the Stewart-Grubbs catalyst was used. To demonstrate the practical utility of our method, methallyl halide CM was successfully employed for the formal total synthesis of a natural product (-)-presphaerene, in which the precursor of the key cyclopentanecarboxylate intermediate was efficiently prepared in three steps.

Analytical and Clinical Evaluation of Chemiluminescent Carcinoembryonic Antigen (CEA) by HISCL-5000 Immunoanalyzer.

OBJECTIVE: The carcinoembryonic antigen (CEA) is coupled with a diagnosis and prognosis for cancers METHODS: The analytical performance of CEA by chemiluminescent immunoassay (HISCL-5000, Sysmex, Kobe, Japan) was evaluated on the basis of precision, linearity, trueness, and method comparison. Clinical evaluation was performed by area under the receiver operating characteristic curve (AU-ROC) curve analysis for lung, stomach and colorectal cancers. RESULTS: Total coefficient of variation (CV) (5.039% to 5.632%), linearity (0.5 to 982 ng/mL) and the percentage bias by trueness verification were less than desirable specifications for imprecision (6.4%) and bias (14.3%). The regression equation was y=0.354+0.957x(r=0.968) from method comparison. AUROC for lung, stomach, and colorectal cancers compared with normal healthy control ranged from 0.908 to 0.967 (cut-off 4.50 to 4.71 ng/mL), and compared with non-malignant benign disease, ranged from 0.578 to 0.721 (cut-off 8 to 20.70 ng/mL). CONCLUSIONS: CEA by HISCL-5000 immunoassay provided reliable performance. Comorbidities should be considered for interpretation of CEA.

Neural correlates of anxiety under interrogation in guilt or innocence contexts.

Interrogation elicits anxiety in individuals under scrutiny regardless of their innocence, and thus, anxious responses to interrogation should be differentiated from deceptive behavior in practical lie detection settings. Despite its importance, not many empirical studies have yet been done to separate the effects of interrogation from the acts of lying or guilt state. The present fMRI study attempted to identify neural substrates of anxious responses under interrogation in either innocent or guilt contexts by developing a modified "Doubt" game. Participants in the guilt condition showed higher brain activations in the right central-executive network and bilateral basal ganglia. Regardless of the person's innocence, we observed higher activation of the salience, theory of mind and sensory-motor networks-areas associated with anxiety-related responses in the interrogative condition, compared to the waived conditions. We further explored two different types of anxious responses under interrogation-true detection anxiety in the guilty (true positive) and false detection anxiety in the innocent (false positive). Differential neural responses across these two conditions were captured at the caudate, thalamus, ventral anterior cingulate and ventromedial prefrontal cortex. We conclude that anxiety is a common neural response to interrogation, regardless of an individual's innocence, and that there are detectable differences in neural responses for true positive and false positive anxious responses under interrogation. The results of our study highlight a need to isolate complex cognitive processes involved in the deceptive acts from the emotional and regulatory responses to interrogation in lie detection schemes.

Analytical evaluation and clinical application of insulin and C-peptide by a whole blood, lateral flow, point of care (POC) assay system.

The analytical performance and clinical application of measuring insulin and connecting peptide (C-peptide) by point of care (POC) assay were evaluated. A POC assay system (SelexOn, Osang Healthcare Inc., Anyang-si, Korea) was evaluated for precision, linearity, limit of blank (LOB), and limit of detection (LOD). Method comparison was performed with the Cobas Elecsys insulin and C-peptide assay (Roche Diagnostics GmbH, Mannheim, Germany) using 215 and 201 patient specimens for insulin and C-peptide, respectively. For clinical application, insulin resistance indices were studied. Homeostasis model assessment (HOMA) 1 and 2, Quantitative insulin sensitivity check index (QUIKI), fasting insulin resistance index (FIRI), and other indices were evaluated. The coefficient of variation (CV) of imprecision for low, medium, and high concentrations was 10.8%1, 15.99%, and 12.05%, respectively, for insulin and 9.21%, 13.51%, and 13.77%, respectively, for C-peptide. The linearity was validated to 839.78 pmol/L for insulin and to 17.30 nmol/L for C-peptide. LOB and LOD were 8.05 and 9.72 pmol/L for insulin and 0.05 and 0.08 nmol/L for C-peptide, respectively. For the method comparison, the regression equation was y = 1.259x - 8.818 (r = 0.957) for insulin and y = 1.163x - 0.088 (r = 0.985) for C-peptide. The ROC value and overall accuracy were as follows: HOMA2 (C-peptide), 0.809, 79.7%; TyG, 0.788, 73.6%; CPR, 0.775, 74.8%; HOMA1, 0.725, 70.3%; QUIKI, 0.720, 70.3%; FIRI, 0.715, 70.1%; McAuley, 0.658, 65.1%; HOMA2 (Insulin), 0.645, 64.7%; Raynaud, 0.611, 61.4%, respectively. The POC assay system for insulin and C-peptide provided reliable results through a rapid and simple test that could be applied to clinical settings.

Comparison of Six Commercial Diagnostic Tests for the Detection of Dengue Virus Non-Structural-1 Antigen and IgM/IgG Antibodies.

ELISAs and rapid diagnostic tests (RDTs) are widely used for diagnosing dengue virus (DENV) infection. Using 138 single blood samples, we compared the ability to detect non-structural (NS)-1 antigen and anti-DENV IgM/IgG antibodies among (1) DENV Detect NS1 ELISA, DENV Detect IgM capture ELISA and DENV Detect IgG ELISA (InBios International, Inc.); (2) Anti-Dengue virus IgM Human ELISA and Anti-Dengue virus IgG Human ELISA (Abcam); (3) Dengue virus NS1 ELISA, Anti-Dengue virus ELISA (IgM) and Anti-Dengue virus ELISA (IgG) (Euroimmun); (4) Asan Easy Test Dengue NS1 Ag 100 and Asan Easy Test Dengue IgG/IgM (Asan Pharm); (5) SD BIOLINE Dengue Duo (Standard Diagnostics); and (6) Ichroma Dengue NS1 and Ichroma Dengue IgG/IgM (Boditech Med). For NS1 antigen detection, InBios and Euroimmun showed higher sensitivities (100%) than the RDTs (42.9-64.3%). All tests demonstrated variable sensitivities for IgM (38.1-90.5%) and IgG (65.7-100.0%). InBios and Boditech Med demonstrated higher sensitivity (95.6% and 88.2%, respectively) than the other tests for combined NS1 antigen and IgM antibody. Five NS1 antigen tests had good agreement (92.8-98.6%) without showing positivity for chikungunya. However, all IgG tests demonstrated potential false-positivity with variable ranges. Clinical laboratories should note performance variations across tests and potential cross-reactivity.

Diagnostic Accuracy of the Risk of Ovarian Malignancy Algorithm in Clinical Practice at a Single Hospital in Korea.

BACKGROUND: The risk of ovarian malignancy algorithm (ROMA) is used for assessing ovarian cancer risk in women with a pelvic mass. Its diagnostic accuracy is variable. We investigated whether the clinically acceptable minimal sensitivity of >80.0% could be obtained with the suggested cutoff of 7.4%/25.3% for pre/postmenopausal women and with adjusted cutoffs set to a specificity of ≥75.0% or a sensitivity of 95.0%, in a hospital with a lower ovarian cancer (OC) prevalence than previously reported. METHODS: ROMA scores were calculated from measurements of human epididymis protein 4 and cancer antigen 125 in blood specimens from 443 patients with a pelvic mass. The ROMA-based risk group was compared against biopsy (N=309) or clinical follow-up with imaging (N=134) results. The ROMA sensitivity and specificity for predicting epithelial OC (EOC) and borderline ovarian tumor (BOT) were calculated for the suggested and adjusted cutoff values. RESULTS: When targeting BOT and EOC, the prevalence was 7.4% and sensitivity and specificity at the suggested cutoff were 63.6% and 90.7%, respectively. Sensitivity was 81.8% at the 4.65%/13.71% cutoff set to a specificity of 75.0%. When targeting only EOC, the prevalence was 4.1% and sensitivity and specificity at the suggested cutoff were 77.8% and 89.4%, respectively. Sensitivity was 88.9% at the 4.78%/14.35% cutoff set to a specificity of 75.0%. CONCLUSIONS: The sensitivity of ROMA was lower than expected when using the suggested cutoff. When using the adjusted cutoff, its sensitivity reached 80.0%.

Stereoselective Protection-Free Asymmetric Total Synthesis of (+)-Chamuvarinin, a Potent Anticancer and Antitrypanosomal Agent: Substrate-Controlled Construction of the Adjacently Linked Oxatricyclic Core by Internal Alkylation.

A stereoselective protection-free asymmetric total synthesis of (+)-chamuvarinin (1), a potent anticancer and antitrypanosomal agent, has been accomplished. The adjacently linked [bis(tetrahydrofuran)]tetrahydropyran (THF-THF-THP) core of this natural product with seven stereogenic centers was constructed in a completely substrate-controlled fashion. The inter-ring stereochemistry ( threo,threo,threo) of the oxatricyclic core was established in a stereoselective fashion by a chelation-controlled Keck allylation, whereas the intraring cis or trans relative stereochemistry was controlled by a stereoselective internal alkylation.

Flavonoids interfere with NLRP3 inflammasome activation.

NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome is a component of innate immunity, and is responsible for producing mature IL-1ß and -18. Several flavonoids were found to affect inflammasome pathway, but the mechanism of action is still obscure. To elucidate the effects on NLRP3 inflammasome pathway and to determine the structure-activity relationships, NLRP3 inflammasome in differentiated THP-1 cells was activated via treatment with monosodium urate (MSU) crystals. Levels of mature IL-1ß, NLRP3 inflammasome components and apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain) (ASC) oligomerization were investigated and the mechanisms of action were also elucidated. Among the 56 flavonoids initially tested, only flavone, 2',4'-dihhydroxyflavone, 3',4'-dichloroflavone, 4',5,7-trihydroxyflavone (apigenin), 3,4',5,7-tetrahydroxyflavone (kaempferol) and 3,3',4',5,7-pentahydroxyflavone (quercetin) significantly inhibited IL-1ß production at 10 µM. Apigenin, kaempferol and 3',4'-dichloroflavone inhibited ASC oligomerization without affecting the ASC level in cell lysates. Apigenin also inhibited absent in melanoma 2 (AIM2) inflammasome-related pathway, but not NLR family CARD domain-containing protein 4 (NLRC4) inflammasome activation. The action of apigenin on NLRP3 inflammasome activation is mediated partly via inhibition of phosphorylation of spleen tyrosine kinase/protein tyrosine kinase 2 (Syk/Pyk2) pathway. Furthermore, orally administered apigenin (100 mg/kg) strongly reduced the number of neutrophils and monocytes in MSU-induced peritonitis in mice. The present study, for the first time, demonstrated the structure-activity profiles of flavonoids in NLRP3 inflammasome activation and mechanisms of cellular action. Certain flavonoids including apigenin are expected to ameliorate the inflammatory symptoms in autoinflammatory diseases associated with NLRP3 inflammasome activation.