Wogonin inhibits hepatoma cell proliferation by targeting miR-27b-5p/YWHAZ axis.

Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid compound in herbal plants, can suppress growth in hepatocellular carcinoma (HCC). However, the microRNA (miRNA) expression profiles that are influenced by wogonin have not been thoroughly described. To explore the novel miRNAs and the biological mechanism underlying the effect of wogonin on HCC cells. The effect of wogonin on Huh7 cell growth was assessed both in vitro and in vivo. The expression profiles of miRNAs were obtained by small RNA sequencing. Luciferase reporter experiment and bioinformatics analysis were conducted to determine whether tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) can bind to miR-27b-5p. Effects of the ectopic expression of YWHAZ and miR-27b-5p on Huh7 cells proliferation and apoptosis were evaluated. Furthermore, the cell cycle, apoptosis and multiple signaling pathway-related molecules were detected by Western blot analysis. Wogonin substantially inhibited the growth of Huh7 cells both in vitro and in vivo. Seventy miRNAs exhibited greater than twofold changes in wogonin-treated cells. Upregulation of miR-27b-5p inhibited Huh7 cell proliferation, and the anticancer effect of wogonin was reversed after miR-27b-5p knockdown. miR-27b-5p directly targeted YWHAZ in HCC cells. The proliferation-inhibiting effect of miR-27b-5p was revoked by YWHAZ overexpression. Meanwhile, inhibition of HCC growth was achieved by downregulating YWHAZ. Wogonin exerted antitumor activity through multiple signaling molecules, such as focal adhesion kinase, protein kinase B, mammalian target of rapamycin and molecules related to apoptosis and cell cycle by upregulating miR-27b-5p and downregulating YWHAZ. Our findings suggest that miR-27b-5p/YWHAZ axis contributes to the inhibitory effect of wogonin in HCC by targeting related genes and multiple signaling pathways.

Evaluation of the mechanisms of intron loss and gain in the social amoebae Dictyostelium.

BACKGROUND: Spliceosomal introns are a common feature of eukaryotic genomes. To approach a comprehensive understanding of intron evolution on Earth, studies should look beyond repeatedly studied groups such as animals, plants, and fungi. The slime mold Dictyostelium belongs to a supergroup of eukaryotes not covered in previous studies. RESULTS: We found 441 precise intron losses in Dictyostelium discoideum and 202 precise intron losses in Dictyostelium purpureum. Consistent with these observations, Dictyostelium discoideum was found to have significantly more copies of reverse transcriptase genes than Dictyostelium purpureum. We also found that the lost introns are significantly further from the 5' end of genes than the conserved introns. Adjacent introns were prone to be lost simultaneously in Dictyostelium discoideum. In both Dictyostelium species, the exonic sequences flanking lost introns were found to have a significantly higher GC content than those flanking conserved introns. Together, these observations support a reverse-transcription model of intron loss in which intron losses were caused by gene conversion between genomic DNA and cDNA reverse transcribed from mature mRNA. We also identified two imprecise intron losses in Dictyostelium discoideum that may have resulted from genomic deletions. Ninety-eight putative intron gains were also observed. Consistent with previous studies of other lineages, the source sequences were found in only a small number of cases, with only two instances of intron gain identified in Dictyostelium discoideum. CONCLUSIONS: Although they diverged very early from animals and fungi, Dictyostelium species have similar mechanisms of intron loss.

Modifiable factors mediating the effects of educational attainment on gestational diabetes mellitus: A two-step Mendelian randomization study.

BACKGROUND: Although there is currently a wealth of evidence to indicate that maternal educational attainment is associated with gestational diabetes mellitus (GDM), the specific modifiable risk factors that mediate the causal relationship between these two variables have yet to be identified. AIM: To identify the specific modifiable risk factors that mediate the causal relationship between the level of maternal education and GDM. METHODS: Mendelian randomization (MR) was conducted using data from genome-wide association studies of European populations. We initially performed a two-sample MR analysis using data on genetic variants associated with the duration of education as instruments, and subsequently adopted a two-step MR approach using metabolic and lifestyle factors as mediators to examine the mechanisms underlying the relationship between the level of maternal education and risk of developing GDM. In addition, we calculated the proportions of total causal effects mediated by identified metabolic and lifestyle factors. RESULTS: A genetically predicted higher educational attainment was found to be associated with a lower risk of developing GDM (OR: 0.71, 95%CI: 0.60-0.84). Among the metabolic factors assessed, four emerged as potential mediators of the education-GDM association, which, ranked by mediated proportions, were as follows: Waist-to-hip-ratio (31.56%, 95%CI: 12.38%-50.70%), body mass index (19.20%, 95%CI: 12.03%-26.42%), high-density lipoprotein cholesterol (12.81%, 95%CI: 8.65%-17.05%), and apolipoprotein A-1 (7.70%, 95%CI: 4.32%-11.05%). These findings proved to be robust to sensitivity analyses. CONCLUSION: Our findings indicate a causal relationship between lower levels of maternal education and the risk of developing GDM can be partly explained by adverse metabolic profiles.

Evidence and possible mechanism of Scutellaria baicalensis and its bioactive compounds for hepatocellular carcinoma treatment.

BACKGROUND: Traditional Chinese medicines have been reported to have outstanding effects in the treating of hepatocellular carcinoma. Scutellaria baicalensis (S. baicalensis) has demonstrated anti-tumor, anti-angiogenic, and anti-inflammatory properties. Baicalein, wogonin, and baicalin are the main pharmacologically bioactive compounds of S. baicalensis. METHODS: Eight electronic databases were searched to select articles published from their inception to 30 May 2022. For selected articles, clinical and preclinical data was obtained on the use of S. baicalensis and its bioactive compounds in hepatocellular carcinoma therapy. Statistical analyses were performed using RevMan version 5.3 and Stata software. Quality assessment of the studies was performed using Cochrane and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE)'s risk of bias tools. RESULTS: Seven clinical and 17 preclinical in vivo studies along with 31 in vitro studies were included in this research. Meta-analysis showed that a Chinese herbal medicine preparation, with S. baicalensis as the sovereign herb, combined with Transcatheter arterial chemoembolization (TACE) or primary treatment, could lead to a significantly improved tumor objective response rate (Risk ratio (RR) = 1.57, 95% confidence interval (CI): [1.30, 1.90], p < 0.00001). Scutellaria baicalensis-based extracts (standard mean difference (SMD) = -0.86, 95%CI: [-1.20, -0.53], p < 0.00001), baicalein (SMD = -4.80, 95%CI: [-6.66, - 2.95], p < 0.00001), baicalin (SMD = -2.28, 95%CI [-3.26, -1.30], p < 0.00001) and wogonin (SMD = -1.41, 95%CI [-2.26, -0.57], p < 0.00001) slowed tumor growth in vivo. These outcomes might be linked to the mechanism by which S. baicalensis promotes apoptosis, induces autophagy, and blocks the expression of vascular endothelial growth factor (p < 0.05). CONCLUSION: Based on experimental and clinical evidence, we believe that S. baicalensis and its bioactive compounds have therapeutic potential and plausible mechanisms of action against hepatocellular carcinoma, in terms of efficacy and safety.

XinLi formula, a traditional Chinese decoction, alleviates chronic heart failure via regulating the interaction of AGTR1 and AQP1.

BACKGROUND: XinLi formula (XLF) is a traditional Chinese medicine used in clinical practice to treat chronic heart failure (CHF) in humans, with remarkable curative effect. However, the mechanism remains unknown. PURPOSE: The goal of the current investigation was to determine how XLF affected CHF in a rat model of the condition brought on by ligation of the left anterior descending coronary artery, and to investigate the underlying mechanism. STUDY DESIGN AND METHODS: Cardiac function was detected by echocardiography. The contents of myocardial enzymes, Ang II, ALD, TGF-ß1, and inflammatory factors were measured by ELISA. Myocardial injury and myocardial fibrosis were evaluated by HE and Masson staining. Myocardial edema was assessed by cardiac mass index and transmission electron microscopy. Using Western blot and immunohistochemistry to examining the protein expression of inflammasome, TGF-ß1, AGTR1, and AQP1 in the left ventricle. Furthermore, the interaction of AGTR1 and AQP1 was evaluated by co-immunoprecipitation. RESULTS: XLF attenuated myocardial enzymes and myocardial injury, and improved cardiac function in rats with CHF after myocardial infarction. It also reduced Ang II and ALD levels in CHF rats, and suppressed the expression of AGTR1 and TGF-ß1, finally alleviated myocardial fibrosis. By mechanism, XLF inhibited the expression of NLRP3 inflammasome proteins, reduced the plasma contents of IL-1ß, IL-18, IL-6 and TNF-α. Additionally, XLF inhibited the expression of AQP1 and the interaction of AGTR1 and AQP1, alleviating myocardial edema. The common structure of the main chemical constituents of XLF were glycoside compounds with glycosyl. CONCLUSION: XLF ameliorated CHF, which was evidenced by the alleviation of myocardial fibrosis by inhibiting AGTR1/NLRP3 signal, as well as the attenuation of myocardial edema by suppressing the interaction of AGTR1 and AQP1.

Intron losses and gains in the nematodes.

BACKGROUND: The evolution of spliceosomal introns has been widely studied among various eukaryotic groups. Researchers nearly reached the consensuses on the pattern and the mechanisms of intron losses and gains across eukaryotes. However, according to previous studies that analyzed a few genes or genomes, Nematoda seems to be an eccentric group. RESULTS: Taking advantage of the recent accumulation of sequenced genomes, we extensively analyzed the intron losses and gains using 104 nematode genomes across all the five Clades of the phylum. Nematodes have a wide range of intron density, from less than one to more than nine per kbp coding sequence. The rates of intron losses and gains exhibit significant heterogeneity both across different nematode lineages and across different evolutionary stages of the same lineage. The frequency of intron losses far exceeds that of intron gains. Five pieces of evidence supporting the model of cDNA-mediated intron loss have been observed in ten Caenorhabditis species, the dominance of the precise intron losses, frequent loss of adjacent introns, high-level expression of the intron-lost genes, preferential losses of short introns, and the preferential losses of introns close to 3'-ends of genes. Like studies in most eukaryotic groups, we cannot find the source sequences for the limited number of intron gains detected in the Caenorhabditis genomes. CONCLUSIONS: These results indicate that nematodes are a typical eukaryotic group rather than an outlier in intron evolution.

Intron gain by tandem genomic duplication: a novel case in a potato gene encoding RNA-dependent RNA polymerase.

The origin and subsequent accumulation of spliceosomal introns are prominent events in the evolution of eukaryotic gene structure. However, the mechanisms underlying intron gain remain unclear because there are few proven cases of recently gained introns. In an RNA-dependent RNA polymerase (RdRp) gene, we found that a tandem duplication occurred after the divergence of potato and its wild relatives among other Solanum plants. The duplicated sequence crosses the intron-exon boundary of the first intron and the second exon. A new intron was detected at this duplicated region, and it includes a small previously exonic segment of the upstream copy of the duplicated sequence and the intronic segment of the downstream copy of the duplicated sequence. The donor site of this new intron was directly obtained from the small previously exonic segment. Most of the splicing signals were inherited directly from the parental intron/exon structure, including a putative branch site, the polypyrimidine tract, the 3' splicing site, two putative exonic splicing enhancers, and the GC contents differed between the intron and exon. In the widely cited model of intron gain by tandem genomic duplication, the duplication of an AGGT-containing exonic segment provides the GT and AG splicing sites for the new intron. Our results illustrate that the tandem duplication model of intron gain should be diverse in terms of obtaining the proper splicing signals.

Comparison of the anti-ulcer activity between the crude and bran-processed Atractylodes lancea in the rat model of gastric ulcer induced by acetic acid.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes lancea (AL, Compositae, Chinese name: Cangzhu; Japanese name: Sou-ju-tsu) has been used traditionally for the treatment of various diseases such as digestive disorders, rheumatic diseases, and influenza in China, Korea and Japan. The crude AL and AL bran-processed are both listed in the Chinese Pharmacopoeia. However, the differences between the effects of the crude and AL bran-processed on gastric ulcer were poorly understood, and the mechanisms for the treatment of gastric ulcer were not clear. This study aimed at comparing the anti-ulcer effects between the crude AL and AL processed in acetic acid induced model in rats and evaluating the mechanisms of action involved in the anti-ulcer properties of AL. MATERIALS AND METHODS: The model of gastric ulcer was imitated by acetic acid in rats, and AL was gavaged. The serum and gastric tissues were collected. The levels of epidermal growth factor (EGF), trefoil factor2 (TFF2), tumor necrosis factor-α (TNF-α), interleukin 6, 8 (IL-6, 8) and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of EGF, TFF2, TNF-α, and IL-8 in stomach were analyzed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, histopathological changes were evaluated by hematoxylin and eosin (HE) stain. The protein expressions of EGF, TFF2, TNF-α, and IL-8 were examined by immunohistochemistry in stomach. RESULTS: The results demonstrated that the damage of gastric tissue was obviously alleviated and the productions of TNF-α, IL-8, IL-6, and PGE2 and the mRNA expressions of TNF-α, and IL-8 were notably inhibited. Furthermore, the productions of EGF and TFF2 and the mRNA expressions of EGF and TFF2 were significantly stimulated by both crude AL and AL processed in a dose-dependent manner. Compared with the crude AL, the processed AL was more effective. CONCLUSION: The AL processed had more satisfactory effects in treatment of gastric-ulcer than the crude AL. The anti-ulcer effects of AL could be attributed to the anti-inflammatory properties via down-regulating TNF-α, IL-8, IL-6 and PGE2 and to the gastroprotective effects via up-regulating EGF and TFF2.

Imprecise intron losses are less frequent than precise intron losses but are not rare in plants.

UNLABELLED: In this study, we identified 19 intron losses, including 11 precise intron losses (PILs), six imprecise intron losses (IILs), one de-exonization, and one exon deletion in tomato and potato, and 17 IILs in Arabidopsis thaliana. Comparative analysis of related genomes confirmed that all of the IILs have been fixed during evolution. Consistent with previous studies, our results indicate that PILs are a major type of intron loss. However, at least in plants, IILs are unlikely to be as rare as previously reported. REVIEWERS: This article was reviewed by Jun Yu and Zhang Zhang. For complete reviews, see the Reviewers' Reports section.

Rational design of carbon and TiO2 assembly materials: covered or strewn, which is better for photocatalysis?

The rational design of carbonaceous hybrid nanostructures is very important for obtaining high photoactivity. TiO2 particles strewn with an optimal quantity of carbon nanodots have a much higher photoactivity than that of TiO2 covered with a carbon layer, showing the importance of carbon morphology in the photocatalysis of carbonaceous hybrid nanostructures.