Moxibustion improves motor function by down-regulating SNX5 and inhibiting ferroptosis in neurons of corpus striatum in mice with Parkinson's disease. / 艾灸调控SNX5å¯¹å¸•é‡‘æ£®ç— æ¨¡åž‹å°é¼ ç¥žç»å ƒé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. METHODS: C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 µL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe2+, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. RESULTS: Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (P<0.01), and strikingly decreased in the moxibustion group relevant to the model group (P<0.01). The immunofluorescence intensity of TH in the substantia nigra, the ratio of GSH/GSSG, and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased (P<0.01, P<0.05), while the contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the decreased immunofluorescence intensity of TH, GSH/GSSH, and the expression levels of GPX4 and FTH1 mRNAs and proteins, and the increased contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion may improve motor dysfunction in PD mice, which may be related to its effects in down-regulating the expression of SNX5, promoting the synthesis of GSH, decreasing the contents of Fe2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.

Draft Genome of a Blister Beetle Mylabris aulica.

Mylabris aulica is a widely distributed blister beetle of the Meloidae family. It has the ability to synthesize a potent defensive secretion that includes cantharidin, a toxic compound used to treat many major illnesses. However, owing to the lack of genetic studies on cantharidin biosynthesis in M. aulica, the commercial use of this species is less extensive than that of other blister beetle species in China. This study reports a draft assembly and possible genes and pathways related to cantharidin biosynthesis for the M. aulica blister beetle using nanopore sequencing data. The draft genome assembly size was 288.5 Mb with a 467.8 Kb N50, and a repeat content of 50.62%. An integrated gene finding pipeline performed for assembly obtained 16,500 protein coding genes. Benchmarking universal single-copy orthologs assessment showed that this gene set included 94.4% complete Insecta universal single-copy orthologs. Over 99% of these genes were assigned functional annotations in the gene ontology, Kyoto Encyclopedia of Genes and Genomes, or Genbank non-redundant databases. Comparative genomic analysis showed that the completeness and continuity of our assembly was better than those of Hycleus cichorii and Hycleus phaleratus blister beetle genomes. The analysis of homologous orthologous genes and inference from evolutionary history imply that the Mylabris and Hycleus genera are genetically close, have a similar genetic background, and have differentiated within one million years. This M. aulica genome assembly provides a valuable resource for future blister beetle studies and will contribute to cantharidin biosynthesis.

[Small intestine motility and gastrointestinal hormone levels in irritable bowel syndrome].

OBJECTIVE: To investigate the relationship between interdigestive migrating motor complex (MMC) and plasma gastrointestinal hormones in patients with diarrhea or constipation-predominant irritable bowel syndrome (IBS) to elucidate the pathophysiology of IBS. METHODS: A small intestine manometry was used to record the MMC cycles for at least 4-6 h in 19 IBS patients and 10 healthy volunteers. The plasma gastrointestinal hormone levels were examined according to altered MMC phases. RESULTS: Compared with the healthy controls, IBS-D patients exhibited shortened duration of the small intestinal MMC cycle, prolonged phase III duration with greater amplitude, as well as faster propagation velocity, whereas the contrary alterations were found in IBS-C patients. The peak plasma motilin level occurred in phase III of the MMC cycle. The plasma somatostatin level was higher in IBS groups than in the healthy controls, but comparable between the diarrhea and constipation groups. Plasma 5-hydroxytryptamine showed periodical fluctuations with the phases of MMC cycles, reaching the peak level in phase II. IBS-D patients had higher 5-hydroxytryptamine levels than IBS-C patients and the healthy controls. CONCLUSIONS: Plasma hormone levels are correlated with the MMC cycles, and the hormone level changes and small intestine motility disorder may play important roles in IBS pathophysiology.