Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Shen-Qi-Jiang-Tang granule ameliorates diabetic nephropathy via modulating tumor necrosis factor signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Qi-Jiang-Tang granule (SQJTG), a classic traditional Chinese medicine (TCM) prescription, has been widely used in clinical for diabetes, especially type Ⅱ diabetes. Previous anti-diabetic studies stumbled across that SQJTG has a potential kidney protective effect on diabetic nephropathy (DN). However, the protective mechanism of SQJTG on DN still needs to be explored. AIM OF THE STUDY: The purpose of the present study was to explore the therapeutic effect of SQJTG on DN through both bioinformatics analysis and in vivo experiments. METHODS AND MATERIALS: The TCMIP database was used for screening potential compounds and targets of SQJTG, and the GeneCards, OMIM, DrugBank, and TTD databases were used for collecting DN-related genes. Then protein-protein interaction analysis for the common targets of SQJTG and DN was performed by the STRING database. Meanwhile, KEGG and GO were carried out using the Metascape and DAVID databases. In vivo experiments, to testify the potential kidney protective effects of SQJTG, STZ-induced DN mice with different dosages of SQJTG treatment were collected and the renal tissues were detected by H&E, PAS, Masson and TUNEL staining. Immunohistochemistry and immunoblotting were used to assess the proteins' expressions. Flow cytometry and ELISA assay were used to detect the levels of pro-inflammatory cytokines. RESULTS: Among the 338 compounds ascertained by SQJTG, there were 789 related targets as well. Moreover, 1,221 DN-related targets were predicted and 20 core targets were screened by the PPI analyses. According to GO and KEGG pathway analysis, SQJTG may affect DN via the TNF pathway. For the in vivo experiments, renal histomorphological examinations demonstrated that SQJTG treatment significantly ameliorated STZ-induced kidney damage and had a dosage dependence. Meanwhile, mice with DN were found to have dramatic increases in IL-1, TNF-α, IL-6, and IL-12, but markedly decreased after administration of SQJTG. In addition, the protein levels of TNF signaling molecules, like p-P65, p-JNK, and p-p38, showed significantly elevated in kidney tissues of DN mice and attenuated after SQJTG treatment. CONCLUSIONS: SQJTG exerts a kidney protective effect in DN mice via modulating TNF signaling pathways, and it has promising applications for the treatment of DN.

Comparison of mitogenomes of three Petalocephala species (Hemiptera: Cicadellidae: Ledrinae) and their phylogenetic analysis.

Ledrinae is a unique group of leafhoppers with a distinct appearance. Petalocephala is the largest Ledrinae genus that is difficult to identify except by dissecting the male genitals. To date, research on Ledrinae is relatively less compared with other leafhoppers. Therefore, to better understand this group, we sequenced and analyzed three complete Petalocephala mitochondrial genomes. We comparatively analyzed these general Petalocephala genomic features (including size, AT content, AT/GC skew, 13 protein-coding gene nucleotide compositions, etc.), and predicted 22 transfer RNA secondary structures. We obtained highly consistent phylogenetic results within Cicadellidae based on mitogenomic data using the maximum likelihood and Bayesian methods. Our results showed that all subfamilies were monophyletic and had a high node support rate, and there was a sister group relationship between Ledrinae and all other leafhopper groups. Furthermore, treehoppers were found to originate from leafhoppers and showed sister group relationships with Megophthalminae. Within Ledrinae, all phylogenetic trees supporting phylogenetic relationships were as follows: ([P. dicondylica + P. gongshanensis] + [Tituria pyramidata + [Ledra auditura + P. gongshanensis]]) Based on the complete mitogenome phylogenetic analysis and the comparison of morphological characteristics, we propose that Petalocephala is not monophyletic.

Anti-inflammatory active components of the roots of Datura metel.

One new phenolic glycoside, methyl 3,4-dihydroxyphenylacetate-4-O-[2-O-ß-D-apisoyl-6-O-(2-hydroxybenzoyl)]-ß-D-glucopyranoside (1), together with 10 known compounds (2-11), were isolated from the roots of Datura metel. The structures of these compounds were elucidated on the basis of their spectroscopic data. Furthermore, the in vitro anti-inflammatory activities of compounds 1-11 were evaluated.[Formula: see text].

Structural and phylogenetic implications of the complete mitochondrial genome of Ledra auditura.

We sequenced and annotated the first complete mitochondrial genome (mitogenome) of Ledra auditura (Hemiptera: Cicadellidae: Ledrinae) and reconstructed phylogenetic relationships among 47 species (including 2 outgroup species) on the basis of 3 datasets using maximum likelihood (ML) and Bayesian inference (BI) analyses. The complete L. auditura mitogenome (length, 16,094 bp) comprises 37 genes [13 protein-coding genes (PCGs), 22 tRNAs, and 2 rRNAs], 1 control region, and 2 long non-coding regions. The first long non-coding region (length, 211 bp) is located between tRNA-I and tRNA-Q and the second region (length, 994 bp) between tRNA-S2 and ND1. All PCGs show ATN (Met/Ile) as their start codon and TAR as their stop codon. Except tRNA-S1 (AGN), which lacks the dihydrouridine arm, all tRNAs can fold into the typical cloverleaf secondary structure. The complete L. auditura mitogenome shows a base composition bias of 76.3% A + T (A = 29.9%, T = 46.4%, G = 13.3%, and C = 10.5%), negative AT skew of -0.22, and positive GC skew of 0.12. In ML and BI analyses, L. auditura was clustered with Evacanthus heimianus (Hemiptera: Cicadellidae: Evacanthinae) with strong branch support.

Vitamin C induces human melanoma A375 cell apoptosis via Bax- and Bcl-2-mediated mitochondrial pathways.

Melanoma is the most malignant type of skin cancer and is resistant to numerous chemotherapeutic and radiotherapy-based treatment approaches due to the activation of rapid and reversible pro-survival signaling pathways. As a result, patients will often present with a poor prognosis. Therefore, novel preventive methods and treatments are urgently required for patients with melanoma. Vitamin C (also known as L-ascorbic acid) is a water-soluble vitamin that is widely used as a dietary additive and has been demonstrated to exhibit anti-cancer properties. In the present study, the effects of vitamin C in human melanoma A375 cells, and the mechanisms underlying these effects were investigated. Vitamin C potently suppressed human melanoma A375 cell proliferation by inducing apoptosis in A375 cells. Induction of apoptosis was related to caspase-9 and caspase-3 activation and the mitochondrial membrane potential of A375 cells significantly decreased in the presence of vitamin C. Furthermore, vitamin C induced apoptosis in A375 cells by activating the Bax- and Bcl-2-mediated mitochondrial pathway. These results indicate that vitamin C may be a potentially useful clinical anti-tumor drug for treating patients with melanoma.

Isoliquiritigenin Induces Mitochondrial Dysfunction and Apoptosis by Inhibiting mitoNEET in a Reactive Oxygen Species-Dependent Manner in A375 Human Melanoma Cells.

The mitochondrial protein mitoNEET is a type of iron-sulfur protein localized to the outer membrane of mitochondria and is involved in a variety of human pathologies including cystic fibrosis, diabetes, muscle atrophy, and neurodegeneration. In the current study, we found that isoliquiritigenin (ISL), one of the components of the root of Glycyrrhiza glabra L., could decrease the expression of mitoNEET in A375 melanoma cells. We also demonstrated that mitoNEET could regulate the content of reactive oxygen species (ROS), by showing that the ISL-mediated increase in the cellular ROS content could be mitigated by the mitoNEET overexpression. We also confirmed the important role of ROS in ISL-treated A375 cells. The increased apoptosis rate and the decreased mitochondrial membrane potential were mitigated by the overexpression of mitoNEET in A375 cells. These findings indicated that ISL could decrease the expression of mitoNEET, which regulated ROS content and subsequently induced mitochondrial dysfunction and apoptosis in A375 cells. Our findings also highlight mitoNEET as a promising mitochondrial target for cancer therapy.

Reprogramming induced by isoliquiritigenin diminishes melanoma cachexia through mTORC2-AKT-GSK3ß signaling.

Isoliquiritigenin (ISL), a member of the flavonoids, is known to have anti-tumor activity in vitro and in vivo. The effect of ISL on reprogramming in cancer cells, however, remains elusive. In this study, we investigated the effect of ISL on reprogramming in human melanoma A375 cells. ISL (15 µg/ml) significantly inhibited A375 cell proliferation, anchorage independent cell proliferation and G2/M cell cycle arrest after ISL exposure for 24 h. However, there were no significant changes in apoptosis rate. Terminal differentiation indicators (melanin content, melanogenesis mRNA expression, tyrosinase (TYR) activity) were all up-regulated by ISL treatment. In ISL-treated cells, glucose uptake, lactate levels and mRNA expression levels of GLUT1 and HK2 were significantly decreased, and accompanied by an increase in O2 consumption rate (OCR) and adenosine triphosphate (ATP) deficiency. Protein expression levels of mTORC2-AKT-GSK3ß signaling pathway components (mTOR, p-mTOR, RICTOR, p-AKT, p-GSK3ß) decreased significantly after ISL treatment. Co-treatment of ISL and the mTOR-specific inhibitor Ku-0063794 had a synergistic effect on the inhibition of proliferation, and increased melanin content and TYR activity. Glucose uptake and lactate levels decreased more significantly than treatment with ISL alone. These findings indicate that ISL induced reprogramming in A375 melanoma cells by activating mTORC2-AKT-GSK3ß signaling.

[Influence of Submerged Plants on Microbial Community Structure in Sediment of Hongze Lake].

Phospholipid fatty acids (PLFAs) method was applied to analyze the influence of submerged plants on sediment microbial community structure, in order to investigate the changes of sediment microbial community structure for different kinds of the submerged plants in different growth periods. Particularly, Potamogeton crispus L., Potamogeton pectinatus L and the mixed group were chosen as the typical submerged plants in Hongze Lake for investigation in this paper. The results indicated that the change of total PLFAs in different periods was significant, on the contrary, the PLFA change for different groups in the same period was insignificant. The values of G⁺ PLFA/G⁻ PLFA in the submerged plant group were also highly related to the different growth periods, which demonstrated that the root function of the submerged plant had a severe impact on the microbial community in sediment. Furthermore, some environmental factors, such as Temperature, pH, TOC and DO, were correlated to characteristic phospholipid of PLFAs in sediment, which means the environmental factors could also affect the microbial community structure.

[Characteristics of Organic Phosphorus Fractions in the Sediments of the Black Water Aggregation in Lake Taihu].

Potential release of phosphorus in lake sediments depends largely on the fractions and distribution of organic phosphorus. MaoDu was chosen as the research area in the west of Lake Taihu. The chemical forms of the surface sediments were investigated by the Ivannoff extraction methods. The results showed that the main organic phosphorus form of sediments at different sampling places was humic acid-OP. It accounted for 35% of the total organic phosphorus. Horizontal distribution: Total organic phosphorus content from the shore to the middle of total showed a trend of rising after decline; vertical distribution: Total organic phosphorus content was the lowest in 2-6 cm and the highest in 4-8 cm. Various phosphorus content followed the order of humic acid-OP > residual-OP > HCl-OP > fulvic acid-OP; the relative content of NaHCO3-OP in the total organic phosphorus content showed a trend of rising followed by reduction and then rising again from the shore to the middle, cyanobacteria residue deposition increased the content of NaHCO3-OP in sediment. Contents of NaHCO3-OP and humic acid-OP both first reduced, then increased and finally reduced in the vertical distribution, the content of NaHCO3-OP was the lowest in 4-6 cm and humic acid-OP was the highest in 4-8 cm. HCl-OP and fulvic-OP decreased with increasing depth in the vertical distribution. The content of residual-OP showed stable tendency in the vertical direction and was about 45 µg·g-1. Labile OP and pH, DO, the depth of water were significantly negatively correlated, OM and NaOH-Pi were significantly correlated with total organic phosphorus, labile OP, moderately labile OP and nonlabile OP. Three components of organic phosphorus had bio-availability and played an important role in lake eutrophication. The increase of the content of labile OP might promote the black water aggregation (BWA) in cyanobacteria accumulation.