The combined anticancer of peanut skin procyanidins and resveratrol to CACO-2 colorectal cancer cells.

Colorectal cancer is one of the leading causes of cancer deaths worldwide. Currently, chemotherapy is the primary way for colorectal cancer, but with severe side effects. Therefore, it is urgent to find safer and more effective adjuvant treatment methods. At present, natural active substances are promising alternatives, as numerous studies have demonstrated possible synergistic anticancer effects in plant-active polyphenols. In the present study, the combined effect of procyanidins (PC) (from peanut skin) and resveratrol (RES) (from peanut buds) on the synergistic anticancer potential was investigated. CACO-2 and HCT-8 cells were served as colorectal cancer models, and HEPG-2 and HUH-7 cells were served as liver cancer models to observe the effects of PC and RES alone or in combination on the growth and proliferation of these four types of cancer cells. The results revealed that both PC and RES could inhibit the cells' proliferation in a manner with concentration-dependent, but they exerted synergistic anticancer effects only on CACO-2 cells. PC and RES could synergistically inhibit CACO-2 cell clone formation, inducing apoptosis of CACO-2 cells and blocking their cell cycle in G0/G1 phase. Additionally, as observed by the results of Western blot assay, the combined effect of PC and RES also inhibited the phosphorylation of Thr308, Ser473, and ERK and promoted the phosphorylation of IKBα and NF-κB in CACO-2 cells. These findings collectively indicate that PC combined with RES might exert synergistic anticancer effects by regulating AKT, ERK, and NF-κB signaling pathways.

The Peanut Skin Procyanidins Attenuate DSS-Induced Ulcerative Colitis in C57BL/6 Mice.

Polyphenols from peanut skin have been reported to possess many beneficial functions for human health, including anti-oxidative, antibacterial, anticancer, and other activities. To date, however, its anti-inflammatory effect and the underlying mechanism remain unclear. In this study, the anti-inflammatory effect of peanut skin procyanidins extract (PSPE) and peanut skin procyanidins (PSPc) were investigated by a dextran sodium sulfate (DSS)-induced colitis mouse model. The results showed that both PSPE and PSPc supplementation reversed the DSS-induced body weight loss and reduced disease activity index (DAI) values, accompanied by enhanced goblet cell numbers and tight junction protein claudin-1 expression in the colon. PSPE and PSPc treatment also suppressed the inflammatory responses and oxidative stress in the colon by down-regulating IL-1ß, TNF-α, and MDA expressions. Meanwhile, PSPE and PSPc significantly altered the gut microbiota composition by increasing the relative abundance of Clostridium XlVb and Anaerotruncus, and inhibiting the relative abundance of Alistipes at the genus level. PSPE and PSPc also significantly elevated the production of short-chain fatty acids (SCFAs) in mice with colitis. The correlation analysis suggested that the protective effects of PSPE and PSPc on colitis might be related to the alteration of gut microbiota composition and the formation of SCFAs. In conclusion, the current research indicates that supplementation of PSPE and PSPc could be a promising nutritional strategy for colitis prevention and treatment.

Small GTPase FoSec4-Mediated Protein Secretion Is Important for Polarized Growth, Reproduction and Pathogenicity in the Banana Fusarium Wilt Fungus Fusarium odoratissimum.

Apical secretion at hyphal tips is important for the growth and development of filamentous fungi. In this study, we analyzed the role of the Rab GTPases FoSec4 involved in the secretion of the banana wilt fungal pathogen Fusarium odoratissimum. We found that the deletion of FoSEC4 affects the activity of extracellular hydrolases and protein secretion, indicating that FoSec4 plays an important role in the regulation of protein secretion in F. odoratissimum. As a typical Rab GTPase, Sec4 participates in the Rab cycle through the conversion between the active GTP-bound state and the inactive GDP-bound state, which is regulated by guanine nucleate exchange factors (GEFs) and GTPase-activating proteins (GAPs). We further found that FoSec2 can interact with dominant-negative FoSec4 (GDP-bound and nucleotide-free form, FoSec4DN), and that FoGyp5 can interact with dominant active FoSec4 (GTP-bound and constitutively active form, FoSec4CA). We evaluated the biofunctions of FoSec4, FoSec2 and FoGyp5, and found that FoSec4 is involved in the regulation of vegetative growth, reproduction, pathogenicity and the environmental stress response of F. odoratissimum, and that FocSec2 and FoGyp5 perform biofunctions consistent with FoSec4, indicating that FoSec2 and FoGyp5 may work as the GEF and the GAP, respectively, of FoSec4 in F. odoratissimum. We further found that the amino-terminal region and Sec2 domain are essential for the biological functions of FoSec2, while the carboxyl-terminal region and Tre-2/Bub2/Cdc16 (TBC) domain are essential for the biological functions of FoGyp5. In addition, FoSec4 mainly accumulated at the hyphal tips and partially colocalized with Spitzenkörper; however, FoGyp5 accumulated at the periphery of Spitzenkörper, suggesting that FoGyp5 may recognize and inactivate FoSec4 at a specific location in hyphal tips.

Current progress on pathogenicity-related transcription factors in Fusarium oxysporum.

Fusarium oxysporum is a well-known soilborne plant pathogen that causes severe vascular wilt in economically important crops worldwide. During the infection process, F. oxysporum not only secretes various virulence factors, such as cell wall-degrading enzymes (CWDEs), effectors, and mycotoxins, that potentially play important roles in fungal pathogenicity but it must also respond to extrinsic abiotic stresses from the environment and the host. Over 700 transcription factors (TFs) have been predicted in the genome of F. oxysporum, but only 26 TFs have been functionally characterized in various formae speciales of F. oxysporum. Among these TFs, a total of 23 belonging to 10 families are required for pathogenesis through various mechanisms and pathways, and the zinc finger TF family is the largest family among these 10 families, which consists of 15 TFs that have been functionally characterized in F. oxysporum. In this review, we report current research progress on the 26 functionally analysed TFs in F. oxysporum and sort them into four groups based on their roles in F. oxysporum pathogenicity. Furthermore, we summarize and compare the biofunctions, involved pathways, putative targets, and homologs of these TFs and analyse the relationships among them. This review provides a systematic analysis of the regulation of virulence-related genes and facilitates further mechanistic analysis of TFs important in F. oxysporum virulence.

Fusarium oxysporum f. sp. lycopersici C2H2 transcription factor FolCzf1 is required for conidiation, fusaric acid production, and early host infection.

The soil-borne, asexual fungus Fusarium oxysporum f.sp. lycopersici (Fol) is a causal agent of tomato wilt disease. The infection process of Fol comprises root recognition, adhesion, penetration, colonization of the root cortex and hyphal proliferation within the xylem vessels, which are under the regulation of virulence-involved transcription factors (TFs). In this study, we identified a gene, designated FolCZF1, which encodes a C2H2 TF in Fol. The homologs of FolCzf1 are also known to affect pathogenicity in F. graminearum and Magnaporthe oryzae on wheat and rice, respectively. We learned that FolCZF1 transcript level is upregulated in conidia and early host infection stage, which led us to hypothesize that FolCzf1 is associated with early host infection in Fol. The FolCZF1 deletion mutant (ΔFolCZF1) exhibited defects in growth rate, conidiation, conidia morphology and a complete loss of virulence on tomato root. Further microscopic observation showed that ΔFolCZF1 can penetrate the root but the primary infection hypha cannot extend its colonization inside the host tissue, suggesting that FolCzf1 TF plays an important role in early infection. Fusaric acid, a secondary metabolite produced by Fusarium species, is suggested as a virulence factor in many crop diseases. We found that FolCzf1 plays a critical role in fusaric acid production by regulating the expression of fusaric acid biosynthesis genes. In summary, FolCzf1 is required for conidiation, secondary metabolism, and early host infection in Fol, and we propose that homologs of FolCzf1 are required for early parasitic growth in other plant pathogenic filamentous fungi.