Mechanisms of ginseng in pancreatic cancer metastasis: A network pharmacology analysis

It has been shown that ginsenosides can inhibit proliferation, migration, and invasion of pancreatic cancer (PC) cells, and promote apoptosis of PC cells. However, the potential mechanisms of ginseng in treating PC metastasis (PCM) have not been fully elucidated. In this study, we employed an integrated bioinformatics approach of network pharmacology analysis. By selecting common targets of diseases and drugs, a drug-component-target-disease network was constructed to analyze the biological functions and signaling pathways involved in the targets. A total of 6 PC samples were includedd, which were divided into primary PC group (PANC-1, n=3) and metastatic PC group. A total of 9263 differentially expressed genes (DEGs) and 14 PC target genes were identified. According to the network pharmacology analysis, we found that ginsenoside Rg3 was associated with the treatment of PCM and identified 6 potential targets. Among them, CD44, EGFR, KRAS, and PRNP were the main DEGs related to the treatment of PC by ginsenoside Rg3. These genes were mainly enriched in the Proteoglycans in Cancer pathway, and KRAS, EGFR, and CD44 were upregulated in the pathway, which may be affected by the ginsenoside Rg3. This provides a new direction for further research on the mechanisms of ginseng in PCM

Fungicides Reduce the Abundance of Yeast-like Symbionts and Survival of White-Backed Planthopper Sogatella furcifera (Homoptera: Delphacidae)

The white-backed planthopper (WBPH) Sogatella furcifera is one of the most harmful pests of rice in Southeast Asia. The fat body of WBPH harbors intracellular yeast-like symbionts (YLS). YLS are vertically transmitted to WBPH offspring by transovarial infection. YLS play an important role in the WBPH life cycle. YLS diversity and function have been extensively studied in the brown planthopper (BPH) and small brown planthopper but not in WBPH, even though a novel strategy for controlling the BPH based on suppressing YLS has been proposed. Here, using denaturing gradient gel electrophoresis, we identified 12 unique fungal sequences among YLS of WBPH, and five of them represented uncultured fungi. We then fed WBPH with rice plants treated with different fungicides [70% propineb wettable powder (WP) (PR), 70% propamocarb hydrochloride aqueous solution (AS) (PH), 25% trifloxystrobin and 50% tebuconazole water-dispersible granules (WG) (TT), 40% pyrimethanil suspension concentrate (SC) (PY), and 50% iprodione SC (IP)] and evaluated their effects on YLS abundance and WBPH survival rate. Both YLS abundance and adult WBPH survival rate were significantly decreased upon feeding fungicide-treated rice plants, and exposure to 50% IP resulted in the strongest reduction. The abundance of two Sf-YLS species (Ascomycetes symbiotes and Cla-like symbiotes) was significantly reduced upon exposure to 50% IP. The counts of Ascomycetes symbiotes, the most abundant YLS species, were also suppressed by the other fungicides tested. In conclusion, 50% IP was the most effective fungicide, reducing YLS abundance and WBPH survival rate under controlled conditions, suggesting its potential use to control WBPH

Base-Promoted Tandem Synthesis of 2‑Substituted Indoles and <i>N</i>‑Fused Polycyclic Indoles

Herein is developed a base-promoted approach for the synthesis of C2-substituted indoles and N-fused polycyclic indoles via 5-endo-dig cyclization of 2-alkynyl anilines, followed by a 1,3′-acyl migration or a dearomatizing Michael addition process. A range of N–H free indoles and 8,9-dihydropyrido[1,2-a]indol-6(7H)-one scaffolds were synthesized in good to excellent yields with broad scope

Involvement of Endoplasmic Reticulum Stress in Capsaicin-Induced Apoptosis of Human Pancreatic Cancer Cells

Capsaicin, main pungent ingredient of hot chilli peppers, has been shown to have anticarcinogenic effect on various cancer cells through multiple mechanisms. In this study, we investigated the apoptotic effect of capsaicin on human pancreatic cancer cells in both in vitro and in vivo systems, as well as the possible mechanisms involved. In vitro, treatment of both the pancreatic cancer cells (PANC-1 and SW1990) with capsaicin resulted in cells growth inhibition, G0/G1 phase arrest, and apoptosis in a dose-dependent manner. Knockdown of growth arrest- and DNA damage-inducible gene 153 (GADD153), a marker of the endoplasmic-reticulum-stress- (ERS-) mediated apoptosis pathway, by specific siRNA attenuated capsaicin-induced apoptosis both in PANC-1 and SW1990 cells. Moreover, in vivo studies capsaicin effectively inhibited the growth and metabolism of pancreatic cancer and prolonged the survival time of pancreatic cancer xenograft tumor-induced mice. Furthermore, capsaicin increased the expression of some key ERS markers, including glucose-regulated protein 78 (GRP78), phosphoprotein kinase-like endoplasmic reticulum kinase (phosphoPERK), and phosphoeukaryotic initiation factor-2α (phospho-eIF2α), activating transcription factor 4 (ATF4) and GADD153 in tumor tissues. In conclusion, we for the first time provide important evidence to support the involvement of ERS in the induction of apoptosis in pancreatic cancer cells by capsaicin

Flowchart showing generation and identification of ECFP knockout mutants based on transgenic PUbB2 P61 x HWE hybrids.

<p>Five groups of Cas9/sgRNA constructs were each micro-injected into ~500–700 double-hemizygous embryos (G₀). All surviving G₀ individuals were outcrossed to HWE and pooled. All G₁ individuals of each pool were screened for the ECFP knockout phenotype. Pools containing individuals with ECFP knockout phenotype were again outcrossed to HWE to generate G₂. DNA was extracted and sequenced from G₀ adults and from G₁ and G₂ larvae showing ECFP knockout phenotype and also from groups of G₁ larvae, which did not show a mutant phenotype.</p

Transformation data of PUbB2 P61 x HWE embryos injected with different CRISPR/Cas9 constructs

<p>KO: knockout.</p><p>Transformation data of PUbB2 P61 x HWE embryos injected with different CRISPR/Cas9 constructs</p

Proportion of different eye marker phenotypes among G₁ and G₂ larvae of pools P41, P49, P55, and family F82.

<p>*PUBB2 P61 x HWE embryos (G₀) were injected with CRISPR/Cas9 RNA constructs.</p><p>**G₂ mutants x HWE.</p><p>Proportion of different eye marker phenotypes among G₁ and G₂ larvae of pools P41, P49, P55, and family F82.</p

Schematic representation of the transgene in <i>Ae. aegypti</i> line PUbB2 P61 and the ECFP gene depicting sg35 and sg13 target sites.

<p>A single copy of the transgene is shown. The protospacer adjacent motifs (PAM) are indicated in red. Abbreviations: pB left, pB right = <i>piggyBac</i> transposon left or right arm; svA = SV40 polyA signal; ECFP = cyan fluorescent protein gene; 3xP3 = eye-specific synthetic promoter; attR, attL = right or left PhiC31 attachment site; DsRed = red fluorescent protein gene; v5B2 = Flockhouse virus B2 gene; <i>PUb</i> = <i>Ae</i>. <i>aegypti</i> poly-ubiquitin promoter.</p