Preparation and characterisation of kaempferol composite carrier solid dispersion: evaluation of its application in preventing soybean oil spoilage.

Kaempferol (KPF) can be used as a natural antioxidant and food additive in food processing. However, the poor solubility of KPF limited its bioavailability and application. In order to improve the solubility of KPF, kaempferol composite carrier solid dispersion (KPF-CC-SD) was prepared and the process was optimised. When the ratio of KPF: CA (citric acid): Soluplus reached 1:4:6, the dissolution rate was the highest, and the sample was stable over 12 weeks. The characterisation results indicated that KPF-CC-SD exists in an amorphous form. Peroxidation value and acid value of soybean oil showed that the preservation effect of KPF-CC-SD was better than that of KPF, and the inhibition effect of KPF-CC-SD on acid value was better than that of butylated hydroxytoluene. In conclusion, KPF-CC-SD can change the solubility, crystal form and spatial stability of KPF through the carrier, which has a great application prospect in the field of food preservation.

Association among physical activity, anxiety and oral health status in Chinese university students: A cross-sectional study.

Background: Evidence is limited regarding the relationship among physical activity, anxiety, and oral health in Chinese university students. This cross-sectional investigation aimed to assess the potential relationship between physical activity, anxiety, and oral health conditions among university students in China. Methods: An online questionnaire measuring physical activity, anxiety status, and oral health condition was completed by 1604 university students. The International Physical Activity Questionnaire Short Form (IPAQ-SF) and Generalized Anxiety Disorder-7 (GAD-7) were selected to evaluate physical activity and anxiety, respectively. Oral health condition was assessed through several self-reported variables, including self-reported toothache, gingival bleeding, frequency of tooth brushing, and use of dental floss. Multivariate logistic regression was performed to analyze the underlying relationship between outcome variables. The control variables included age, height, weight, gender, whether only one-child, education level, parental education level, smoking status, drinking habits, and length of sleep. Path analysis was conducted to disentangle the association between physical activity, anxiety, and oral health conditions. Results: Among 1604 university students, 666 (41.5 %) were males and 938 (58.5 %) were females, with an average of 21.9 ± 2.8 years. Only 833 (51.9 %) reported sufficient physical activity, while 684 (42.6 %) of the subjects displayed varying degrees of anxiety. Self-reported gingival bleeding was associated with insufficient physical activity (OR = 1.25; 95%CI: 1.02-1.55), anxiety (OR = 0.45; 95%CI: 0.27-0.74), frequency of tooth brushing (OR = 0.75; 95%CI: 0.60-0.95) and use of dental floss (OR = 0.75; 95%CI: 0.59-0.96), while toothache was not directly influenced by the physical activity and anxiety among university students. Anxiety markedly mediated the relationship between physical activity and oral health conditions. Conclusions: Anxiety was considered a factor associated with the level of physical activity, tooth brushing habits, and self-reported gingival bleeding among university students. Further investigations are required to elucidate whether oral health conditions could be enhanced through the improvement of anxiety and physical activity.

Overview of the pharmacokinetics and pharmacodynamics of URAT1 inhibitors for the treatment of hyperuricemia and gout.

INTRODUCTION: Hyperuricemia is a common metabolic disease, which is a risk factor for gouty arthritis and ureteral stones and may also lead to cardiovascular and chronic kidney disease (CDK). Therefore, hyperuricemia should be treated early. Xanthine oxidase inhibitors (XOIs) and uricosuric agents (UAs), which target uric acid, are two types of medications that are used to treat gout and hyperuricemia. XOIs stop the body from producing excessive uric acid, while UAs eliminate it rapidly via the kidneys. Urate transporter 1 (URAT1) belongs to the organic anion transporter family (OAT) and is specifically localized to the apical membrane of the epithelial cells of proximal tubules. Unlike other organic anion transporter family members, URAT1 identifies and transports organic anions that are primarily responsible for urate transport. AREAS COVERED: This article reviews the pharmacokinetics and pharmacodynamics of the existing URAT1 inhibitors to serve as a reference for subsequent drug studies. EXPERT OPINION: The URAT1 inhibitors that are currently used as clinical drugs mainly include dotinurad, benzbromarone, and probenecid. Results indicate that RDEA3170 may be the most promising inhibitor, in addition to SHR4640, URC-102, and MBX-102, which are in the early stages of development.

Bioactivity and Component Analysis of Water Extract of Sophora japonica against Hyperuricemia by Inhibiting Xanthine Oxidase Activity.

Hyperuricemia (HUA) is a metabolic condition caused by excessive production or low excretion of uric acid (UA) in the body. Xanthine oxidase (XOD) is the key enzyme in the process of metabolism purines to generate UA. In this study, the in vitro inhibitory effect of water extract of the flower bud of Sophora japonica (WESJ) on XOD was investigated by ultraviolet spectrophotometry. A mice model of HUA was constructed to explore the effect of WESJ on UA levels and the mechanism of action on renal function. Based on Box-Behnken design, the optimal extraction process of WESJ was determined to extract Sophora japonica twice with 8 times of water, 0.5 h each time. Pharmacological results showed that low, medium, and high doses of WESJ (200, 400, 600 mg/kg) could significantly reduce serum UA level, inhibit the activity of XOD in blood and liver, and have a protective effect on kidney damage caused by high UA. Through UPLC-Q-TOF-MS/MS analysis, 214 compounds were identified in WESJ, including flavonoids, polyphenols, triterpenoids, organic acids, and others. The rat serum of WESJ was analyzed, and 23 prototype components entering the blood were identified, including 15 flavonoids and polyphenols, which may be the main bioactive components. In conclusion, flavonoids and polyphenols in WESJ may reduce the level of UA and alleviate kidney damage by inhibiting the activity of XOD. WESJ is expected to be used as a plant-based food and dietary supplement for the treatment of HUA.

Icariin Inhibits Intestinal Inflammation of DSS-Induced Colitis Mice Through Modulating Intestinal Flora Abundance and Modulating p-p65/p65 Molecule.

BACKGROUND: Ulcerative colitis, as a kind of inflammatory bowel disease (IBD) is characterized by abdominal pain. This study aimed to investigate the effect of icariin (ICA) on the intestinal microflora of colitis mice. METHODS: Fifteen female C57BL/6 mice were randomly divided into the Control group, dextran sodium sulfate (DSS)-induced colitis (DSS) group, and ICA treatment (DSS+ICA) group. The severity of inflammation in DSS-induced colitis mice was evaluated using disease activity scoring (considering weight-loss percentage, stool-shape change, and stool-bleeding scoring). Pathological changes of mice intestinal tract were evaluated using hematoxylin-eosin (HE) staining. Serum levels of TNF-α and IL-6 were detected with enzyme-linked immunosorbent assay. Expressions of p65 and p-p65 (p-p65/p65 ratio) were analyzed using Western blot assay. 16S rDNA sequencing was used to analyze the abundance and composition of intestinal microflora. RESULTS: Compared with DSS group, ICA significantly improved disease activity (P < .05) and reduced inflammatory damage of colon tissues (P < .05) in DSS-induced colitis mice. Compared with the DSS group, mice in the ICA group demonstrated significant weight and colon length (P < .05). ICA significantly inhibited expressions of IL-6 and TNF-α compared to the DSS group (P < .05). p-p65/ p65 ratio in the DSS + ICA group was remarkably enhanced compared to the DSS group (P < .05). ICA significantly reduced the proportion and activity of Bacteroides, Helicobacteraceae, Turicibacter, and significantly increased that of beneficial microflora (Lactobacillus, Lachnospiraceae, Akkermansia), so as improved damages of colon tissues. CONCLUSION: ICA can improve intestinal flora abundance and composition of DSS-induced colitis mice, and inhibit tissue damage and inflammatory response through modulating the p-p65/p65 expression.

A brief review of urate transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia and gout: Current therapeutic options and potential applications.

Hyperuricemia is a common metabolic condition, cause by increased levels of serum urate (SUA). Reduced excretion of uric acid is reported as the key factor of primary hyperuricemia, accounting for approximately 90% of the cases. Urate transporter 1 (URAT1) is a major protein involved in uric acid reabsorption (about 90%). Therefore, URAT1 inhibitors are considered to be a highly effective and promising class of uricosuric agents for treating hyperuricemia. This review summarizes the development of URAT1 inhibitors for the treatment of hyperuricemia, including approved URAT1 inhibitors, URAT1 inhibitors under development in clinical trials, substances with URAT1 inhibitory effects from derivatives and natural products, and conventional drugs with new uses. This review provides new ideas regarding research on URAT1 inhibitors by introducing the structure, properties, and side effects of chemical drugs, as well as the sources and categories of natural drugs. We also discuss new mechanisms of classic drugs, which may provide guidance to many practicing clinicians. The research and discovery of new inhibitors remain in full swing, and tremendous developments are expected in the field.

Genomic and clinical characteristics of MET exon14 alterations in a large cohort of Chinese cancer patients revealed distinct features and a novel resistance mechanism for crizotinib.

Background: Alterations in MET exon 14 (METex14) and its flanking intronic regions have been identified in a variety of cancers. Patients with METex14 alterations often benefit from MET inhibitors such as crizotinib. Given the unique mutation profiles of Chinese lung cancer patients, it is necessary to investigate the prevalence of METex14 alterations in a large cohort of cancer patients. Patients and methods: Cases carrying METex14 alterations were screened from 26,391 Chinese cancer patients by next-generation sequencing (NGS), and the clinicopathologic and molecular characteristics were reviewed. Results: Compared to Western population (~3%), the frequency of METex14 alterations is much lower in Chinese cancer patients (0.7%, n=184) and lung cancer patients (1.1%, n=175). Seventy-eight distinct METex14 alterations, including several novel alteration types were detected. Concurrent MET copy gain and non-exon14 MET mutations were also found. EGFR copy gain (11%) and mutations (8%), KRAS (5%) and PIK3CA (5%), appeared in a mutually exclusive pattern. Female patients contain much less TP53 mutations than male patients (65% vs. 24%, FDR = 0.01). Co-amplification of CDK4 and MDM2, CDK6 and EGFR were identified, which indicated cell cycle dysregulation and EGFR alteration are important co-occurring features in patients with METex 14 alteration. Of 9 tissue specimens having PD-L1 immunohistochemistry (IHC) results, 5 of them (55.5%) were found PD-L1 positive, which is comparable to other types of tumor. In 14 crizotinib-treated patients, the median progression free survival (mPFS) was 7 months. Upon resistance to crizotinib, two patients acquired secondary mutations in MET and one patient acquired BRAF p.K601E that can be a novel resistance mechanism. Conclusion: Chinese cancer patients have a relatively lower frequency of METex14 alterations compared to Western patients. Patients with METex14 alterations showed distinct molecular characteristics and the representative case study showed responses to MET tyrosine kinase inhibitor (TKI).