•Anti-CLI effect of TFACS were systematically investigated at the animal, omics and cellular levels.•Focal adhesion, PI3K/Akt and ferroptosis signalling pathways are key pathways.•Akt1, Pik3ca, NF-κB ...p65, Itga5, Itgb5, Itga6, Prkca, Fn1, Tfrc and Vdac3 were key targets.•Focal adhesion and PI3K/Akt pathways were verified in LPS-stimulated RAW 264.7 macrophages.•Ferroptosis pathway were assessed using erastin-stimulated l-O2 ferroptosis model cells.
Total flavonoids from Astragali Complanati Semen (TFACS), the main active ingredients in Astragali Complanati Semen (ACS), have been shown to have a protective effect on chronic liver injury (CLI), but the hepatoprotective targets and signalling pathways involved are unclear.
The aim of our study was to identify the anti-CLI targets and signalling pathways of TFACS and to comprehensively elucidate its mechanism of action via proteomics analysis combined with in vivo and in vitro experiments.
A CLI mouse model was generated via intraperitoneal injection of carbon tetrachloride (CCl4) (CCl4: olive oil = 1:4, 2 ml/kg, twice a week for 6 weeks). The hepatoprotective effect of TFACS was assessed by observing the pathological structure of the liver and analysing indicators of liver function. The key pathways and targets related to the hepatoprotective effect of TFACS were identified via 4D-label-free quantitative proteomics technology and further verified via in vivo indicator validation and in vitro cell experiments.
TFACS administration significantly normalized the histopathological structure and function of the liver, decreased the levels of inflammatory factors and oxidative stress indicators, and reduced the iron staining area and the levels of hepcidin and iron in the liver compared with those in the CLI model. A total of 424 differentially expressed proteins (DEPs) were identified between the TFACS and model groups, and these DEPs were enriched in the focal adhesion, PI3K-Akt, and ferroptosis pathways. Akt1, Pik3ca, NF-κB p65, Itga5, Itgb5, Itga6, Prkca, Fn1, Tfrc, and Vdac3 were identified as key targets of TFACS. TFACS administration significantly reversed the changes in the gene and protein expression of the key targets compared with those in the model group. In addition, TFACS treatment significantly reduced the levels of inflammatory cytokines and inhibited Akt1, NF-κB p65 and FAK activation in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. In an erastin-induced l-O2 ferroptosis cell model, treatment with TFACS normalized the mitochondrial structure, reduced the protein levels of Tfrc and Vdac3, inhibited lipid peroxidation, and reduced the amount of Fe2+ in the mitochondria.
TFACS protected against CLI, and its mechanism of action may be related to inhibition of the focal adhesion, PI3K/Akt and ferroptosis signalling pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Diverse RNA transcripts acting as competing endogenous RNAs (ceRNAs) can co-regulate each other's expression by competing for shared microRNAs. CCR2 protein, the receptor for CCL2, is implicated in ...cancer progression. However, we found that a higher
mRNA level is remarkably associated with prolonged survival of breast cancer patients. These conflicting results prompted us to study the non-coding function of
mRNA. We found that the
3' untranslated region (UTR) inhibited MDA-MB-231 and MCF-7 cell metastasis by repressing epithelial-mesenchymal transition (EMT)
, and suppressed breast cancer metastasis
Mechanistically, the
3'UTR modulated the expression of the RhoGAP protein STARD13 via acting as a STARD13 ceRNA in a microRNA-dependent and protein coding-independent manner. The
3'UTR blocked the activation of RhoA-ROCK1 pathway, which is the downstream effector of STARD13, and thus decreased the phosphorylation level of myosin light chain 2 (MLC2) and formation of F-actin. Additionally, the function of the
3'UTR was dependent on STARD13 expression. In conclusion, our results confirmed that the
3'UTR acts as a metastasis suppressor by acting as a ceRNA for STARD13 and thus inhibiting RhoA-ROCK1-MLC-F-actin pathway in breast cancer cells.This article has an associated First Person interview with the first author of the paper.
Green synthesis of silver nanoparticles (AgNPs) has been extensively studied by using a variety of plant extracts for applications in biomedical sciences and engineering. However, there are no ...reports on the synthesis of AgNPs by utilizing the berry extract of
Sea Buckthorn
, which is a traditional Chinese medicine and exhibits a wide spectrum of antioxidant, anti-inflammatory and anticancer activities. In this paper, we report an easy and eco-friendly technique for the preparation of AgNPs using the
Sea Buckthorn
berry extract under ultrasonic radiation at ambient temperature and the evaluation of both biosynthesis parameters and biological activities. The UV-visible spectrum and dynamic light scattering (DLS) analysis showed that the size of AgNPs was sensitive to the biosynthesis parameters, such as the pH of the extract, material proportion and reaction time, offering a size-controlled synthetic method for AgNPs. The X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED) and DLS studies showed that the AgNPs (pH 10.0; material proportion 1 : 1; 4 h) had a face-centered cubic (fcc) structure and spherical shape with an average particle size of 27.3 ± 0.2 nm covered by anions, and existed in a monodispersed form with a polydispersity index (PDI) of 0.213. The biosynthesized AgNPs showed potent anticancer activity against human colorectal cancer (HCT116 and SW620), hepatoma cancer (HepG2), breast cancer (MCF-7) and cervical cancer (HeLa) cell lines as well as strong antioxidant activity. The IC
50
values for these five cell lines were 8.77, 4.61, 14.59, 16.05 and 27.98 μg mL
−1
, respectively. However, the biosynthesized AgNPs revealed poor inhibition activities for the growth of
E
.
coli
and
S
.
aureus
. These results confirmed that the
Sea Buckthorn
could be a low-cost, nontoxic and eco-friendly natural resource for the synthesis of AgNPs, which might be useful for the development of new alternative antioxidant and anticancer agents in biomedicine.
Herein, by using the
Sea Buckthorn
berry extract, we present a new eco-friendly approach for green synthesis of AgNPs, which reveal superior antioxidation and anticancer but poor antimicrobial activities.
Colorectal cancer (CRC) ranks third in incidence and second in mortality among all types of cancer, and due to its insidious onset and lack of early symptoms, it is usually diagnosed at a later ...stage. Saponins, a class of compounds abundant in plants, have been reported to possess prominent anti-tumour properties. The use of ginsenoside Rg3 in the clinical setting was authorized by the National Medicinal Products Administration of China. In the present study, total saponins from Rhizoma Panacis Majoris (RPMTG) were prepared, and the pharmacological mechanisms underlying the anti-CRC effects of RPMTG were investigated. The effect of RPMTG on the proliferation, cell cycle progression and apoptosis of HCT116 and SW620 cells were detected by MTT, flow cytometry and western blotting assays, and it was demonstrated that RPMTG could inhibit the proliferation of HCT116 and SW620 cells with IC50 values of 315.8 and 355.1 microg/ml, respectively, induce cell cycle arrest in the S and G.sub.0/G.sub.1 phase, and trigger apoptosis by down-regulating the expression of the anti-apoptotic proteins Bcl-2, Bcl-xL and induced myeloid leukaemia cell differentiation protein Mcl-1, and increasing the expression of the pro-apoptotic proteins Bax and Bad, cleaved caspased-3 and poly(ADP)-ribose polymerase. These findings suggested that RPMTG induced apoptosis through mitochondrial-related pathways. In addition, RPMTG also decreased the expression of phosphorylated (p)-extracellular signal-regulated kinase and increased p-c-Jun N-terminal kinase (p-JNK) and p-p38. Moreover, the effects of RPMTG on cell proliferation and apoptosis were partially reversed when the JNK and p38 mitogen-activated protein kinase (MAPK) pathways were inhibited, indicating that RPMTG triggered apoptosis mainly via regulating JNK and p38 MAPK signalling. Therefore, RPMTG may have potential as an anti-CRC agent, and further evaluations are needed. Key words: RPMTG, colorectal cancer, apoptosis, cell cycle arrest, MAPK signalling pathways
Cancer stem cells, which are a population of cancer cells sharing common properties with normal stem cells, have strong self-renewal ability and multi-lineage differentiation potential to trigger ...tumor proliferation, metastases, and recurrence. From this, targeted therapy for cancer stem cells may be one of the most promising strategies for comprehensive treatment of tumors in the future. We design a facile approach to establish the colon cancer stem cells-selective fluorescent probe based on the low-density lipoprotein (LDL) and the novel AgGa
In
S
quantum dots (AGIS QDs). The AGIS QDs with a high crystallinity are obtained for the first time via cation-exchange protocol of Ga
to In
starting from parent AgInS
QDs. Photoluminescence peak of AGIS QDs can be turned from 502 to 719 nm by regulating the reaction conditions, with the highest quantum yield up to 37%. Subsequently, AGIS QDs-conjugated LDL nanocomposites (NCs) are fabricated, in which a cationic polyelectrolyte was used as a coupling reagent to guarantee the electrostatic self-assembly. The structural integrity and physicochemical properties of the LDL-QDs NCs are found to be maintained in vitro, and the NCs exhibit remarkable biocompatibility. The LDL-QDs can be selectively delivered into cancer stem cells that overexpress LDL receptor, and three-dimensional imaging of cancer stem cells is realized. The results of this study not only demonstrate the versatility of nature-derived lipoprotein nanoparticles, but also confirm the feasibility of electrostatic conjugation using cationic polyelectrolyte, allowing reseachers to design nanoarchitectures for targeted diagnosis and treatment of cancer.
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IJS, KILJ, NUK, PNG, UL, UM
The pathogenesis of acute lung injury (ALI) is complex and it is a common critical illness in clinical practice, seriously threatening the lives of critically ill patients, for which no specific ...molecular marker exists and there is a lack of effective methods for the treatment of ALI. The present study aimed to investigate the mechanism of action of honeysuckle and forsythia in treatment of acute lung injury (ALI) based on network pharmacology and
modeling. The active ingredients and targets of honeysuckle and forsythia were predicted using traditional Chinese medicine systems pharmacology, PubChem and Swiss Target Prediction databases, and the Cytoscape 3.7.2 software was used to construct a drug-component-potential target network. The potential targets were imported into the Search tool for recurring instances of neighboring genes) database to obtain protein-protein interactions and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Targets analysis using Database for Annotation, Visualization, and Integrated Discovery. AutoDock Vina 1.1.2 software was used for docking between key active ingredients and the target proteins to analyze the binding ability of the active ingredients to the primary targets in honeysuckle and forsythia. A total of 64 male BALB/c mice were randomly divided into control, model, positive drug (Lianhua-Qingwen capsule), honeysuckle, forsythia, honeysuckle + forsythia high-, medium- and low-dose groups. Lipopolysaccharide (LPS) was used to induced an ALI model. The lung tissues of the mice were stained with hematoxylin-eosin and the serum levels of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured 4 h after the LPS administration. Reverse transcription-quantitative PCR and western blotting were used to detect NF-κB mRNA and protein expression, respectively. Active ingredients of honeysuckle and forsythia acted on 265 common targets in ALI, which regulated NF-κB, tumor necrosis factor-α (TNF-α) and PI3K-AKT signaling pathway, HIF-1 signalling pathway to slow the inflammatory response in treatment of ALI. In the positive drug group, honeysuckle, forsythia group, honeysuckle + forsythia high-, medium- and low-dose groups, lung tissue damage were significantly decrease compared with the model group, and inflammatory cell infiltration was reduced. Compared with the model group, honeysuckle + forsythia groups experienced decreased damage caused by the LPS and inflammation in the lung tissues and significantly decreased TNF-α and NF-κB and MDA concentration and significantly increased the SOD and GSH-Px activities. The mechanism of the effect of honeysuckle and forsythia on ALI may be mediated by inhibition of TNF-α and NF-κB expression and the activation of antioxidant mechanisms to decrease production of pro-inflammatory cytokines in lung tissue, thus treating ALI.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ternary I–III–VI semiconductor-based nanocrystals (NCs) exhibit a wide range of applications in optoelectronics, photovoltaics, and biolabeling. This motivates the in-depth study of a method to ...synthesize them and explore their optical properties. We present an approach for the synthesis of quaternary CuxAg1−xInSe2 (x = 0–1) NCs by means of the cation exchange reaction starting from AgInSe2 NCs. By tailoring the thermodynamic and kinetic parameters, control over both the composition and bandgap was successfully achieved. The optical properties demonstrated significant nonlinear behavior, whereby the photoluminescence (PL) wavelength and bandgap evolved steeply for a range of x < 0.5 but became invariant when x > 0.5. Optical characterizations indicated that two distinct transition processes, i.e., donor–acceptor pair and free-to-bound recombinations dominated the PL emissions for CuxAg1−xInSe2 NCs with different x values. Furthermore, the obtained NCs were directly modified with phospholipids. In vitro experiments illustrated that the phospholipid-decorated CuxAg1−xInSe2 NCs have excellent biocompatibility and can be used as a fluorescent marker for the fast bioimaging of cancer cells and cancer stem cells in the visible and NIR regions.
Ternary I–III–VI semiconductor-based nanocrystals (NCs) exhibit a wide range of applications in optoelectronics, photovoltaics, and biolabeling. This motivates the in-depth study of a method to ...synthesize them and explore their optical properties. We present an approach for the synthesis of quaternary Cu
x
Ag
1−x
InSe
2
(
x
= 0–1) NCs by means of the cation exchange reaction starting from AgInSe
2
NCs. By tailoring the thermodynamic and kinetic parameters, control over both the composition and bandgap was successfully achieved. The optical properties demonstrated significant nonlinear behavior, whereby the photoluminescence (PL) wavelength and bandgap evolved steeply for a range of
x
< 0.5 but became invariant when
x
> 0.5. Optical characterizations indicated that two distinct transition processes,
i.e.
, donor–acceptor pair and free-to-bound recombinations dominated the PL emissions for Cu
x
Ag
1−x
InSe
2
NCs with different
x
values. Furthermore, the obtained NCs were directly modified with phospholipids.
In vitro
experiments illustrated that the phospholipid-decorated Cu
x
Ag
1−x
InSe
2
NCs have excellent biocompatibility and can be used as a fluorescent marker for the fast bioimaging of cancer cells and cancer stem cells in the visible and NIR regions.
Ternary I-III-VI semiconductor-based nanocrystals (NCs) exhibit a wide range of applications in optoelectronics, photovoltaics, and biolabeling. This motivates the in-depth study of a method to ...synthesize them and explore their optical properties. We present an approach for the synthesis of quaternary Cu
x
Ag
1−
x
InSe
2
(
x
= 0-1) NCs by means of the cation exchange reaction starting from AgInSe
2
NCs. By tailoring the thermodynamic and kinetic parameters, control over both the composition and bandgap was successfully achieved. The optical properties demonstrated significant nonlinear behavior, whereby the photoluminescence (PL) wavelength and bandgap evolved steeply for a range of
x
< 0.5 but became invariant when
x
> 0.5. Optical characterizations indicated that two distinct transition processes,
i.e.
, donor-acceptor pair and free-to-bound recombinations dominated the PL emissions for Cu
x
Ag
1−
x
InSe
2
NCs with different
x
values. Furthermore, the obtained NCs were directly modified with phospholipids.
In vitro
experiments illustrated that the phospholipid-decorated Cu
x
Ag
1−
x
InSe
2
NCs have excellent biocompatibility and can be used as a fluorescent marker for the fast bioimaging of cancer cells and cancer stem cells in the visible and NIR regions.
A novel phospholipid-decorated Cu
x
Ag
1−
x
InSe
2
nanoprobe was fabricated for fast fluorescence imaging of cancer cells and cancer stem cells. A mechanism to understand the PL origin of Cu
x
Ag
1−
x
InSe
2
nanocrystals was proposed.
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