SmDXS5, acting as a molecular valve, plays a key regulatory role in the primary and secondary metabolism of tanshinones in Salvia miltiorrhiza.

Red sage, the dry root and rhizome of the herbaceous plant Salvia miltiorrhiza Bunge, is widely used for treating various diseases. The low content of tanshinones (terpenoids) has always restricted development of the S. miltiorrhiza industry. Here, we found that SmDXS5, a rate-limiting enzyme-coding gene located at the intersection of primary and secondary metabolism, can effectively change the transcription level and secondary metabolome profile of hairy roots of S. miltiorrhiza, and significantly increase the content of tanshinones. Agrobacterium rhizogenes was used to infuse S. miltiorrhiza explants, and hairy roots of S. miltiorrhiza expressing the SmDXS5 gene were obtained successfully. We identified 39 differentially accumulated metabolites (DAMs) by metabolomics based on ultra-high performance liquid chromatography quadrupole exactive mass spectrometry and multivariate statistics. These DAMs might be key metabolites of SmDXS5 gene regulation. RNA sequencing was used to compare gene expression between the hairy roots of the SmDXS5 overexpressing group and the blank control (BC) group. Compared with the BC group, 18,646 differentially expressed genes were obtained: 8994 were upregulated and 9,652 downregulated. The combined transcriptome and metabolome analyses revealed that the mevalonate and methylerythritol phosphate pathways and synthase gene expression levels in the SmDXS5 overexpressing group were upregulated significantly, and the accumulation of tanshinone components was increased significantly, which promoted the process of glycolysis and promoted the transformation of carbohydrates to secondary metabolism. Moreover, the expression of SmPAL, the first rate-limiting enzyme gene of the phenylpropane pathway, decreased, reducing the accumulation of phenolic acid, another secondary metabolite. Therefore, SmDXS5 can be defined as a 'valve' gene, mainly responsible for regulating the distribution of primary and secondary metabolic flow of tanshinones in S. miltiorrhiza, and for other secondary metabolic pathways. The discovery of SmDXS5 and its molecular valve function in regulating primary and secondary metabolism will provide a basis for the industrial production of tanshinone components, and cultivation of high quality S. miltiorrhiza.

[Protective effect of ginsenoside Rg_1 aganist diabetic retinopathy by inhibiting NLRP3 inflammasome in type 2 diabetic mice].

Ginsenoside Rg_1, one of the main active components of precious traditional Chinese medicine Ginseng Radix et Rhizoma, has the anti-oxidative stress, anti-inflammation, anti-aging, neuroprotection, and other pharmacological effects. Diabetic retinopathy(DR), the most common complication of diabetes, is also the main cause of impaired vision and blindness in the middle-aged and the elderly. The latest research shows that ginsenoside Rg_1 can protect patients against DR, but the protection and the mechanism are rarely studied. This study mainly explored the protective effect of ginsenoside Rg_1 against DR in type 2 diabetic mice and the mechanism. High fat diet(HFD) and streptozotocin(STZ) were used to induce type 2 diabetes in mice, and hematoxylin-eosin(HE) staining was employed to observe pathological changes in the retina of mice. The immunohistochemistry was applied to study the localization and expression of nucleotide-binding oligomerization domain-like receptors 3(NLRP3) and vascular endothelial growth factor(VEGF) in retina, and Western blot was used to detect the expression of nuclear factor-kappa B(NF-κB), p-NF-κB, NLRP3, caspase-1, interleukin-1ß(IL-1ß), transient receptor potential channel protein 6(TRPC6), nuclear factor of activated T-cell 2(NFAT2), and VEGF in retina. The results showed that ginsenoside Rg_1 significantly alleviated the pathological injury of retina in type 2 diabetic mice. Immunohistochemistry results demonstrated that ginsenoside Rg_1 significantly decreased the expression of NLRP3 and VEGF in retinal ganglion cells, middle plexiform layer, and outer plexiform layer in type 2 diabetic mice. According to the Western blot results, ginsenoside Rg_1 significantly lowered the expression of p-NF-κB, NLRP3, caspase-1, IL-1ß, TRPC6, NFAT2, and VEGF in retina of type 2 diabetic mice. These findings suggest that ginsenoside Rg_1 can significantly alleviate DR in type 2 diabetic mice, which may be related to inhibition of NLRP3 inflammasome and VEGF. This study provides experimental evidence for the clinical application of ginsenoside Rg_1 in the treatment of DR.

The complete mitochondrial genome of Aucklandia lappa Decne. (Asteraceae, Aucklandia Falc.).

The complete mitochondrial genome of Aucklandia lappa was sequenced for the first time. The mitochondrial genome length was 320,439 bp, with 45.05% GC contents. There were 67 genes annotated, including 31 known protein-coding genes, 25 tRNAs, and six rRNAs. The maximum likelihood method was used to establish the phylogenetic tree of 37 species. Results have shown that A. lappa and Arctium lappa were sister groups. It reveals the genetic relationship between different species and provides a theoretical basis for the establishment of a classification system.

The complete mitochondrial genome of Aconitum kusnezoffii Rchb. (Ranales, Ranunculaceae).

Aconitum kusnezoffii Rchb. is a medicinal plant in the Ranunculaceae family. In this study, we report the first complete mitochondrial genome of A. kusnezoffii. The total length of the mitochondrial genome of A. kusnezoffii is 440,720 bp and the GC content of 46.85%. The mitochondrial genome contained 37 protein-coding genes, 29 tRNAs, and three rRNAs. These data will provide the basis for the systematic evolutionary analysis of Ranunculaceae.

The complete mitochondrial genome of Euonymus alatus (celastraceae, Euonymus L.).

The complete mitochondrial genome of medicinal plant, Euonymus alatus, was sequenced for the first time. The genome sequence is 1,045,106 bp in length (GenBank accession number MW009108), with 44.98% GC contents. There are 72 genes in the genome, including 41 known protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), and three ribosomal RNAs (rRNAs). The phylogenetic trees of 28 species are constructed using the maximum-likelihood method. The information will provide references for phylogenetic research.

The complete mitochondrial genome of Glycyrrhiza uralensis Fisch. (Fabales, Leguminosae).

The complete mitochondrial genome of an important medicinal plant Glycyrrhiza uralensis Fisch. is reported for the first time. The mitochondrial genome sequence of G. uralensis was 463,869 bp in length and had a GC content of 45.19%. The genome contained 40 protein-coding genes (PCGs), 30 transfer RNAs (tRNAs), and three ribosomal RNAs (rRNAs). The phylogenetic tree was built based on 25 plants, using the maximum-likelihood method. These data will provide certain help to determine the taxonomic status of G. uralensis.

Low-grade myofibroblastic sarcoma of gastric cardia on 18F-FDG positron emission tomography/computed tomography: An extremely rare case report.

RATIONALE: Low-grade myofibroblastic sarcoma (LGMS) is a rare mesenchyme-derived tumor, which usually occurs in head, neck (especially tongue and mouth), and limbs. In this report, we described a case of gastric LGMS by F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT), which has not been reported previously. PATIENT CONCERNS: A 51-year-old female patient was admitted to our hospital with upper abdominal discomfort for 1 year and gradually increased eating difficulties over the last 3 months. From gastroscopy, an ulcer of 1.0 cm × 1.2 cm at the entrance of cardia and stiffness of peripheral mucosa were found, leading to suspicion of cardia cancer. F-FDG PET/CT was performed for further diagnosis and staging. DIAGNOSES: According to pathological findings in combination with immunohistochemical features, diagnosis of gastric LGMS was made. INTERVENTIONS: To relieve symptoms of upper gastrointestinal obstruction in the patient, proximal gastrectomy was carried out 1 week after the F-FDG PET/CT scan. OUTCOMES: The patient died due to advanced tumor. LESSONS: F-FDG PET/CT scan showed local thickening of the gastric wall, invasion of adjacent soft tissue, diaphragmatic and peritoneal metastasis at early stage, absence of regional lymph node metastasis, and increased F-FDG metabolism in primary tumor and metastatic tumor.

ΔNp63, CK5/6, TTF-1 and napsin A, a reliable panel to subtype non-small cell lung cancer in biopsy specimens.

Histopathological subtyping of nonsmall cell lung cancer (NSCLC) is currently important in selecting specific therapeutic agents. It can be challenging in distinguishing poorly differentiated lung adenocarcinoma (AC) from squamous cell carcinoma (SCC) on small biopsy samples. This study was aimed to evaluate the utility of a panel of immunohistochemical markers consisting of ΔNp63 (p40), cytokeratins (CK) 5/6, thyroid transcription factor-1 (TTF-1) and napsin A (novel aspartic proteinase of the pepsin family) in subtyping poorly differentiated NSCLC. Forty-eight cases of NSCLC that could not be further classified by examination of hematoxylin-eosin (H&E)-stained slides on biopsy and had subsequent resection specimens were selected. Subtyping of the tumor was based on the resection specimen using the World Health Organization criteria. ΔNp63 was expressed in all 16 SCCs (100%), and was negative in all ACs and LCCs. CK5/6 was positive in 13 of 16 SCCs (81%), and was negative in all ACs and LCCs. TTF-1 was positive in 20 of 25 ACs (80%) and 3 of 7 LCCs (43%), but none of 16 SCCs. Napsin A was positive in 16 of 25 ACs (64%) and was negative in all SCCs and LCCs. Our study shows that a panel including ΔNp63, CK5/6, TTF-1, and napsin A allows correct subclassification of 39 of 48 cases of NSCLC on biopsy and may contribute to refine lung cancer classification in biopsy specimens, remarkably reducing the NSCLC-NOS (not otherwise specified) diagnostic category.