Fucoxanthin is a pigment found in plants and animals such as algae， marine plankton and aquatic shellfish， and holds significant potential for development in the pharmaceutical field. This review introduces the anti-inflammatory， antioxidant， anticancer， anti-obesity， and other pharmacological effects of fucoxanthin， as well as recent advances in drug design research. It was found that fucoxanthin can exert anti-inflammatory and antioxidant effects through mechanisms such as activating AMP- activated protein kinase related signaling pathways， regulating the expression of inflammatory factors， altering microbial stability， thereby improving conditions such as metabolic associated fatty liver disease and colitis. It can exert selective antitumor effects through multi-target synergistic actions； and it was also found that it can exert anti-obesity effects by regulating the intestinal microbiota. Its characteristic functional groups （such as hydroxyl and epoxy groups） possess target specificity and reversible inhibitory properties， making it a suitable template for guiding the design and development of novel drugs， thereby providing new insights for breaking through the limitations of traditional drug design.

Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.

Objective: To investigate the changes of microorganisms and metabolites in joint effusion of patients with Rheumatoid arthritis(RA), Osteoarthritis(OA) and Urarthritis(UA). To provide new ideas for the study of the effect of microbiota on the pathogenesis of arthritis. Methods: Joint effusion samples were collected from 20 patients with RA, 20 patients with OA, and 20 patients with UA. 16S rRNA gene sequencing and untargeted ultra-high performance Liquid chromatography-mass spectrometry(LC-MS) were used to explore the differences in microorganisms and metabolites among the three groups. Pearson correlation analysis was used to detect the correlation between effusion microbiota and metabolites. Results: There were differences in microbial diversity and microbiota composition among the three groups. Combined with VIP>1 from OPLS-DA andP<0.05 from two-tailed Students t-test, 45 differential metabolites(Between RA and OA groups), 38 differential metabolites(Between UA and OA groups) and 16 differential metabolites(Between RA and UA groups), were identified. GO analysis and KEGG pathway analysis showed that the differential metabolic pathways among the three groups were mainly concentrated in citric acid cycle(TCA cycle), nucleotide metabolism, amino acid metabolism and glycolysis pathway. Correlation analysis of joint effusion microbiota and metabolites suggested that bacteria enriched in the three groups of joint effusion, such asPrevotella,Clostridium ruminosus,Prevotellaceae＿UCG-001, were related to many key metabolites such as lysozyme, uric acid, glucose, and L-glutamine. Conclusion This study shows that there are a variety of bacterial flora in joint cavity effusion of RA, OA, and UA patients, and the differential metabolites produced by them are involved in the pathogenesis of the three types of arthritis by affecting a variety of metabolic pathways.

In order to solve the problem of resistance of Pseudomonas aeruginosa to multiple antibiotics, it is an effective way to find inhibitors of P. aeruginosa efflux pump. In this study, 15 new ornithine peptidomimetic derivatives were designed and synthesized by changing the side chain structure of natural amino acids with PAβN, a dipeptide efflux pump inhibitor, and their synergic activity with aztreonam, a monocyclic β-lactam antibiotic, against P. aeruginosa was evaluated. Among them, the representative compound 12b not only enhanced the antibacterial activity of β-lactam antibiotics aztreonam, ceftazidime and meropenem, but also significantly enhanced the antibacterial action of macrolide antibiotics clarithromycin, showing a broad-spectrum synergic sensitization effect. In addition, compound 12b also has a good safety. Preliminary mechanisms suggest that 12b works by directly targeting the efflux transporter MexB. These results provide a new lead compound for the development of a new class of efflux pump inhibitors against P. aeruginosa.

Humans ; Phosphorylation ; Serine ; Protein Serine-Threonine Kinases/metabolism* ; Spasms, Infantile

Objective:To investigate the expression, methylation and prognosis of DKK2 in non-small cell lung cancer, and also its effect and correlation with the sensitivity of hypofractionated radiotherapy sensitivity in non-small cell lung cancer.Methods:qPCR, online database and Kaplan-Meier survival curve were used to detect the expression, methylation and prognosis of DKK2 in NSCLC samples. A549 cells was set as the research objects, and cloning formation experiment and Western blot were used to evaluated the effects of DKK2 on hypofractionated radiotherapy in NSCLC.Results:Compared with the normal tissues, the expression of DKK2 mRNA in NSCLC samples was down-regulaged [ (0.00042±0.0001) vs (0.00065±0.0002), P<0.001]. Data taken from an online methylation database showed that compared with normal tissue, DKK2 hypermethylated in NSCLC, and its methylation was significantly negatively correlated with the mRNA expression. Downregulated DKK2 expression was inversely correlated with its methylation status ( P=0.034). The hypofractionated radiotherapy sensitivity of NSCLC patients was 53.3%. Compared with radiosensitivity group, DKK2 mRNA expression was significantly down-regulated in radioresistance group[ (0.00064±0.0002) vs (0.00043±0.0002), P<0.001]. The progression free survival of radiotherapy sensitive group was better than that of radiotherapy resistant group (median PFS: 21.4 months vs 4.6 months). Ectopic expression of DKK2 in A549 lines inhibited colony formation after irradiation with 4 Gy X-ray radiotherapy. Western blot further showed that restoration of DKK2 expression resulted in upregulation of DNA damage markers γ-H2AX[ (1.00±0.24) vs (3.22±0.41), P<0.001], and the difference was statistically significant. Conclusion:DKK2 expression is downregulated in NSCLC due to methylation, which may be acted as an important target to predict the hypofractionated radiotherapy sensitivity of NSCLC.

In order to explore the functions of genes of key rate-limiting enzymes chalcone isomerase(CHI) and chalcone synthase(CHS) in the biosynthesis of flavonoids in Lonicera macranthoides, this study screened and cloned the cDNA sequences of CHI and CHS genes from the transcriptome data of conventional variety and 'Xianglei' of L. macranthoides. Online bioinformatics analysis software was used to analyze the characteristics of the encoded proteins, and quantitative reverse-transcription polymerase chain reaction(qRT-PCR) to detect the expression of CHI and CHS in different parts of the varieties at different flowering stages. The content of luteo-loside was determined by high performance liquid chromatography(HPLC) and the correlation with the expression of the two genes was analyzed. The results showed that the CHI and CHS of the two varieties contained a 627 bp and 1170 bp open reading frame(ORF), respectively, and the CHI protein and CHS protein were stable, hydrophilic, and non-secretory. qRT-PCR results demonstrated that CHI and CHS of the two varieties were differentially expressed in stems and leaves at different flowering stages, particularly the key stages. Based on HPLC data, luteoloside content was in negative correlation with the relative expression of the genes. Thus, CHI and CHS might regulate the accumulation of flavonoids in L. macranthoides, and the specific functions should be further studied. This study cloned CHI and CHS in L. macranthoides and analyzed their expression for the first time, which laid a basis for investigating the molecular mechanism of the differences in flavonoids such as luteoloside in L. macranthoides and variety breeding.
Acyltransferases/metabolism* ; Chalcone ; Cloning, Molecular ; Intramolecular Lyases ; Lonicera/metabolism* ; Plant Breeding

Objective: To investigate the association of blood lead and blood selenium with serum high-sensitivity C-reactive protein (hs-CRP) among Chinese adults aged 19 to 79 years. Methods: The participants were enrolled from the first wave of China National Human Biomonitoring (CNHBM) conducted from 2017 to 2018. 10 153 participants aged 19 to 79 years were included in this study. Fasting blood samples were obtained from participants. Lead and selenium in whole blood and hs-CRP in serum were measured. Individuals with hs-CRP levels above 3.0 mg/L were defined as elevated hs-CRP. Generalized linear mixed models and restricted cubic spline models were used to analyze the association of blood lead and blood selenium with elevated hs-CRP. Logistic regression models were used to analyze the multiplicative scale and additive scale interaction between blood lead and blood selenium on elevated hs-CRP. Results: The age of participants was (48.91±15.38) years, of which 5 054 (61.47%) were male. 1 181 (11.29%) participants were defined as elevated hs-CRP. After multivariable adjustment, results from generalized linear models showed that compared with participants with the lowest quartile of blood lead, the OR (95%CI) of elevated hs-CRP for participants with the second, third, and highest quartiles were 1.14 (0.94-1.37), 1.25 (1.04-1.52) and 1.38 (1.13-1.68), respectively. When compared with participants with the lowest quartile of blood selenium, the OR (95%CI) of elevated hs-CRP for participants with the second, third and highest quartiles were 0.86 (0.72-1.04), 0.91 (0.76-1.11), and 0.75 (0.61-0.92), respectively. Results from the interaction analysis showed no significant interaction between lead and selenium on elevated hs-CRP. Conclusion: Blood concentration of lead was positively associated with elevated serum hs-CRP, and blood concentration of selenium was inversely related to elevated hs-CRP, while blood lead and selenium did not present interaction on elevated hs-CRP.
Adult ; Aged ; Asians ; Biomarkers ; C-Reactive Protein/analysis* ; China/epidemiology* ; Humans ; Male ; Middle Aged ; Risk Factors ; Selenium ; Young Adult

Objective:To explore the application value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in prenatal diagnosis of isolated corpus callosum abnormality (CCA) fetus.Methods:Fetuses diagnosed with isolated CCA by ultrasound and MRI and receiving invasive prenatal diagnosis in Guangzhou Women and Children′s Medical Center and Qingyuan People′s Hospital from January 2010 to April 2021 were selected. Karyotype analysis and/or CMA [or copy number variation sequencing (CNV-seq)] were performed on all fetal samples, and WES was performed on fetal samples and their parents whose karyotype analysis and/or CMA (or CNV-seq) results were not abnormal.Results:Among 65 fetuses with isolated CCA, 38 cases underwent karyotype analysis, and 3 cases were detected with abnormal karyotypes, with a detection rate of 8% (3/38). A total of 49 fetuses with isolated CCA underwent CMA (or CNV-seq) detection, and 6 cases of pathogenic CNV were detected, the detection rate was 12% (6/49). Among them, the karyotype analysis results were abnormal, and the detection rate of further CMA detection was 1/1. The karyotype results were normal, and the detection rate of further CMA (or CNV-seq) detection was 14% (3/21). The detection rate of CMA as the first-line detection technique was 7% (2/27). A total of 25 fetuses with isolated CCA with negative results of karyotyping and/or CMA were tested by WES, and 9 cases (36%, 9/25) were detected with pathogenic genes. The gradient genetic diagnosis of chromosomal karyotyping, CMA and WES resulted in a definite genetic diagnosis of 26% (17/65) of isolated CCA fetuses.Conclusions:Prenatal genetic diagnosis of isolated CCA fetuses is of great clinical significance. The detection rate of CMA is higher than that of traditional karyotyping. CMA detection could be used as a first-line detection technique for fetuses with isolated CCA. WES could increase the pathogenicity detection rate of fetuses with isolated CCA when karyotype analysis and/or CMA test results are negative.

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors