Selenochemical modification of low molecular weight polysaccharides from Grifola frondosa and the mechanism of their inhibitory effects on gastric cancer cells.

An important micronutrient involved in immune response and antitumor is selenium. LMW-GFP, a polysaccharide extracted from Grifola frondosa seed bodies, has a relatively weak antitumor effect on BGC-823 and MFC cells in vitro, whereas selenium binding to LMW-GFP can significantly increase the in vitro antitumor activity of LMW-GFP. In this study, Se-LMW-GFP was prepared by the HNO3-Na2SeO3 method, and the structures of LMW-GFP and Se-LMW-GFP were characterized by UV-visible spectroscopy of absorption, FTIR spectroscopy, and electron scanning microscopy, and these structural analyses showed that selenium was successfully complexed to LMW-GFP. The selenium content of Se-LMW-GFP was measured to be 2.08 % ± 0.08 % by ICP-MS. The anti-tumor activity of LMW-GFP before and after selenium modification was compared by cellular experiments, and the findings indicated that the anti-tumor activity of Se-LMW-GFP was considerably improved over that of LMW-GFP, and inhibited the proliferation of BGC-823 cells and MFC cells through a combination of the Fas/FasL-mediated exogenous death receptor pathway as well as the endogenous mitochondrial pathway. Our results suggest that Se-LMW-GFP not only has great potential for natural health food and anti-gastric cancer drug development but is also a good selenium supplement.

Hypericum perforatum L. protects against renal function decline in ovariectomy rat model by regulating expressions of NOS3 and AKT1 in AGE-RAGE pathway.

BACKGROUND: Hypericum perforatum L. (HPL) is a potential traditional Chinese medicine. It could promotes menopausal 'kidney-yin deficiency syndrome' that characterized by renal function decline. However, its potential pharmacological effect and mechanism remains unknown. OBJECTIVE: The aim of this study was to investigate whether HPL can improve menopausal renal function decline and to explore its mechanism of action. METHODS: The mainly ingredients of HPL were identified using UPLC-Q-TOF-MS/MS approach, and the potential therapeutic targets of HPL for renal function decline were chose via network pharmacology technique. The key therapeutic metabolites were selected through non-targeted metabolomic and chemometric methods. Then, the network were constructed and the key targets and metabolites were screened. At last, the validation experiments and mechanism exploring were adopted by using Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting assays. RESULTS: mainly ingredients of HPL were identified and determined 17 compounds and 29 targets were chose as mainly active compounds and potential therapeutic targets. Based on OVX induced renal decline rat model, after chemometric analysis, 59 endo-metabolites were selected as key therapeutic metabolites, and AGE-RAGE signal pathway in diabetes complications was enriched as the key pathway. By constructing a "disease-component-target" network, Hyperoside, Quercetrin, and quinic were selected as the key therapeutic compounds, and the AKT1 and NOS3 were selected as the key therapeutic targets. The results of ELISA, RT-PCR and western blot experiments indicated that HPL could rescue the abnormal expressions both of AKT1 and NOS3, as well as their related metabolites distortion. CONCLUSION: Our findings indicated that HPL regulated expression of AKT1 and NOS3 through modulating AGE-RAGE signaling pathway in OVX stimulated rats` renal dysfunction, implicating the potential values of HPL in menopause syndromes therapy.

[Mechanism of Wuling Capsules against hepatic fibrosis based on network pharmacology and animal experiments].

The present study aimed to explore the underlying mechanism of Wuling Capsules in the treatment of hepatic fibrosis(HF) through network pharmacology, molecular docking, and animal experiments. Firstly, the chemical components and targets of Wuling Capsules against HF were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Traditional Chinese Medicines Integrated Database(TCMID), GeneCards, and literature retrieval. The protein-protein interaction(PPI) network analysis was carried out on the common targets by STRING database and Cytoscape 3.9.1 software, and the core targets were screened, followed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. Enrichment analysis was conducted on the core targets and the "drug-core component-target-pathway-disease" network was further constructed. Subsequently, molecular docking between core components and core targets was conducted using AutoDock Vina software to predict the underlying mechanism of action against HF. Finally, an HF model induced by CCl_4 was constructed in rats, and the general signs and liver tissue morphology were observed. HE and Masson staining were used to analyze the liver tissue sections. The effects of Wuling Capsules on the levels of inflammatory factors, hydroxyproline(HYP) levels, and core targets were analyzed by ELISA, RT-PCR, etc. A total of 445 chemical components of Wuling Capsules were screened, corresponding to 3 882 potential targets, intersecting with 1 240 targets of HF, and 47 core targets such as TNF, IL6, INS, and PIK3CA were screened. GO and KEGG enrichment analysis showed that the core targets mainly affected the process of cell stimulation response and metabolic regulation, involving cancer, PI3K-Akt, MAPK, and other signaling pathways. Molecular docking showed that the core components of Wuling Capsules, such as lucidenic acid K, ganoderic acid B, lucidenic acid N, saikosaponin Q2, and neocryptotanshinone, had high affinities with the core targets, such as TNF, IL6 and PIK3CA. Animal experiments showed that Wuling Capsules could reduce fat vacuole, inflammatory infiltration, and collagen deposition in rat liver, decrease the levels of inflammatory cytokines TNF-α, IL-6, and HYP, and downregulated the expressions of PI3K and Akt mRNA. This study suggests that the anti-HF effect of Wuling Capsules may be achieved by regulating the PI3K-Akt signaling pathway, reducing the levels of TNF-α and IL-6 inflammatory factors, and inhibiting the excessive deposition of collagen.

Research on the improvement effect of Saposhnikovia divaricata (Trucz.) Schischk on rheumatoid arthritis based on the "component-target-pathway" association.

OBJECTIVE: To investigate the therapeutic effect and mechanism of the traditional Chinese medicine Saposhnikovia divaricata (Trucz.) Schischk in rats with complete Freund's adjuvant-induced rheumatoid arthritis (RA). METHODS: The chemical targets and RA targets of Saposhnikovia divaricata (Trucz.) Schischk were acquired by the network pharmacological method. The complete Freund's adjuvant-induced rat RA model was used to further explore the mechanism of Saposhnikovia divaricata (Trucz.) Schischk in improving RA. Pathological changes in the volume of toes, body weight and synovial tissues of joints as well as serum inflammatory factor levels before and after the intervention of Saposhnikovia divaricata (Trucz.) Schischk were investigated. The key metabolic pathways were screened by correlations between metabolites and key targets. Finally, a quantitative analysis of key targets and metabolites was experimentally validated. RESULTS: Saposhnikovia divaricata (Trucz.) Schischk administration increased body weight, mitigated foot swelling and downregulated inflammatory cytokine levels in model rats. The histopathology showed that treatment with Saposhnikovia divaricata (Trucz.) Schischk can induce inflammatory cell infiltration and synovial hyperplasia and obviously reduce cartilage injuries, thus improving arthritis symptoms in rats. According to the network pharmacology-metabonomics association analysis results, the purine metabolic signaling pathway might be the key pathway for RA intervention with Saposhnikovia divaricata (Trucz.) Schischk. Targeted metabonomics, Western blotting (WB) and reverse transcription-polymerase chain reaction (RT‒PCR) assays showed that the recombinant adenosine deaminase (ADA) mRNA expression level and metabolic level of inosine in Saposhnikovia divaricata (Trucz.) Schischk administration group were lower than those of the model group. This reflected that Saposhnikovia divaricata (Trucz.) Schischk could improve RA by downregulating ADA mRNA expression levels and the metabolic level of inosine in the purine signaling pathway. CONCLUSION: Based on the "component-disease-target" association analysis, this study concludes that Saposhnikovia divaricata (Trucz.) Schischk improves complete Freund's adjuvant-induced RA symptoms in rats mainly by downregulating ADA mRNA expression levels in the purine metabolic signaling pathway, mitigating foot swelling, improving the levels of serum inflammatory factors (IL-1ß, IL-6 and TNF-α), and decreasing the ADA protein expression level to intervene in purine metabolism.

Poria cum Radix Pini Rescues Barium Chloride-Induced Arrhythmia by Regulating the cGMP-PKG Signalling Pathway Involving ADORA1 in Zebrafish.

The traditional Chinese medicine Poria cum Radix Pini (PRP) is a fungal medicinal material that has been proven to play an important role in the treatment of arrhythmia. However, the mechanism of its effect on arrhythmia is still unclear. In this study, network pharmacology and metabolomics correlation analysis methods were used to determine the key targets, metabolites and potential pathways involved in the effects of PRP on arrhythmia. The results showed that PRP can significantly improve cardiac congestion, shorten the SV-BA interval and reduce the apoptosis of myocardial cells induced by barium chloride in zebrafish. By upregulating the expression of the ADORA1 protein and the levels of adenosine and cGMP metabolites in the cGMP-PKG signalling pathway, PRP can participate in ameliorating arrhythmia. Therefore, we believe that PRP shows great potential for the treatment of arrhythmia.

Taoren-dahuang herb pair reduces eicosanoid metabolite shifts by regulating ADORA2A degradation activity in ischaemia/reperfusion injury rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peach kernel (taoren: TR) is the dried mature seed of peach, Prunus persica (L.) Batsch, which belongs to the Rosaceae family. Rhubarb (dahuang: DH) is the dried root and rhizome of rhubarb (Rheum palmatum L., Rheum officinale Baill., or Rheum tanguticum Maxim. ex Balf.). TR-DH (TD) is a traditional Chinese medicine herb pair that promotes blood circulation and removes blood stasis. In recent years, TD has shown definite benefits in the cardio-cerebrovascular system, but its specific mechanism is not very clear. AIM OF STUDY: The purpose of this study was to explore the mechanism by which TD affects cerebral ischaemia/reperfusion (I/R) injury and to optimize the mixture ratio. METHODS: The affected metabolic pathways in rat brain tissues after I/R were analysed by network pharmacology and verified with animal pharmacological experiments. RESULTS: TD had a certain therapeutic effect on cerebral I/R injury. TD with a TR:DH ratio of 1:1 had the best therapeutic effect. Metabolic pathway analysis showed that the protective mechanism of TD against I/R injury involves mainly regulation of brain tissue ADORA2A protein levels and action on the arachidonic acid (AA) pathway. CONCLUSION: TD can ameliorate cerebral I/R injury by regulating ADORA2A degradation in the AA metabolic pathway to attenuate AA metabolic dysfunction and the inflammatory response.

ER-depletion lowering the 'hypothalamus-uterus-kidney' axis functions by perturbing the renal ERß/Ptgds signalling pathway.

Researchers have long assumed that systematic estrogen fading might contribute to the sustained progression of menopausal degenerate syndromes, although definitive evidence has not been presented. Whether such findings represent a causal contribution or are the result of opportunistic messengers sent from the reproductive system to the brain is also a vital question. We constructed a multiscale network of the ovariectomy (OVX) induced estrogen receptors depletion (ER-depletion) model and integrated targeted proteomic, targeted lipidomic, cytochemical, and histopathological data across three tissues from the ovariectomy rodent model. We found that compared to control rats, OVX rats showed increased renal and uterine prostaglandin D2 synthase (Ptgds) expression and decreased hypothalamic Ptgds expression, abnormal Ptgds metabolites, the degenerate renal function profiles and decreased cognitive ability (learning and memory) in Morris water maze test. Importantly, we observed a regulatory relationship among ER (particularly ERß), the degree of the pathological phenotype, learning behavior test and the 'hypothalamus-uterus-kidney (HUK) axis functions. Collectively, this study elucidates that ER depletion promoted HUK aging is mostly attributed to a renal ERß/Ptgds signalling imbalance.

MicroRNA-132 attenuates LPS-induced inflammatory injury by targeting TRAF6 in neuronal cell line HT-22.

Epilepsy is a common neurological disorder in the central nervous system. Inflammation disrupts the blood-brain barrier (BBB), which is responsible for maintaining brain homeostasis. This study was aimed to investigate the functional role of microRNA (miR)-132 in hippocampal HT-22 cells under lipopolysaccharide (LPS) stimulation. In vitro cell inflammatory model was constructed by LPS stimulation. Inflammatory cell injury was evaluated according to the alterations of cell viability, apoptosis, and expression of inflammatory cytokines. Then, miR-132 level after LPS treatment was assessed. Subsequently, miR-132 was abnormally expressed after cell transfection, and the effects of miR-132 on LPS-induced cell inflammatory injury as well as phosphorylated levels of key kinases in the NF-κB and MAPK kinase (MEK)/ERK pathways were determined. The target gene of miR-132 was virtually screened and verified, and whether miR-132 affected HT-22 cells under LPS stimulation through regulating the target gene was verified. The results showed that the level of miR-132 was down-regulated by LPS in HT-22 cells, and the LPS-induced inflammatory injury could be reduced by miR-132 overexpression. Then, the phosphorylated levels of kinases in the NF-κB and MEK/ERK pathways were decreased by miR-132 overexpression. Tumor necrosis factor receptor-associated factor 6 (TRAF6) was predicted and verified to be a target of miR-132. Moreover, the alterations induced by miR-132 overexpression in the LPS-treated HT-22 cells were abrogated by TRAF6 overexpression. Therefore, we drew the conclusion that LPS down-regulated miR-132 and miR-132 attenuated LPS-induced inflammatory cell injury by targeting TRAF6, along with the inhibition of the NF-κB and MEK/ERK pathways.

NiSe@NiOOH Core-Shell Hyacinth-like Nanostructures on Nickel Foam Synthesized by in Situ Electrochemical Oxidation as an Efficient Electrocatalyst for the Oxygen Evolution Reaction.

NiSe@NiOOH core-shell hyacinth-like nanostructures supported on nickel foam (NF) have been successfully synthesized by a facile solvothermal selenization and subsequent in situ electrochemical oxidation (ISEO). First, the unique NiSe/NF nanopillar arrays were prepared in N,N-dimethylformamide (DMF) as a precursor template that can provide a large surface area, excellent conductivity, and robust support. Next, amorphous NiOOH covering the surface of NiSe nanopillars was fabricated by ISEO, as confirmed by XPS andEDX spectroscopy. SEM images revealed the hyacinth-like morphology of NiSe@NiOOH/NF with NiOOH as the shell and NiSe as the core. The electrochemical performance of NiSe@NiOOH/NF for the oxygen evolution reaction (OER) was investigated. NiSe@NiOOH/NF demonstrates an obviously enhanced OER activity with much lower overpotential of 332 mV at 50 mA cm(-2) compared to other Ni-based electrocatalysts. The low charge-transfer resistance (Rct), large electrochemical double-layer capacitance (Cdl) of electrochemically active surface areas (ECSAs), and excellent long-term stability of NiSe@NiOOH/NF confirm the enhancement of its electrochemical performance for the OER, which can be ascribed to the large amount of active sites derived from the amorphous NiOOH shell and the good conductivity and stability derived from the NiSe core. In addition, the synergistic effect between the NiSe core and NiOOH shell could serve for a highly efficient OER electrocatalyst.

[Roles of long noncoding RNA in lung cancer].

Long noncoding RNAs are a group of noncoding RNAs with a length more than 200 nucleotides. Recent studies have revealed that long noncoding RNAs play an important role in the development and progression of cancer. Lung cancer is the leading cause of cancer-related death all over the world. In this article, we review the roles of long noncoding RNAs in lung cancer to provide new insights into the diagnosis and treatment of the disease.

Effects of catalpol on ATPase and amino acids in gerbils with cerebral ischemia/reperfusion injury.

This study aimed to investigate the effects of catalpol on ATPase and amino acids in gerbils following cerebral ischemia/reperfusion (CI/R) injury. Gerbil model of CI/R was prepared by bilateral common carotid occlusion for 10 min followed by 6 h of reperfusion. Catalpol (5, 10 or 20 mg/kg per day) was injected intraperitoneally for 3 days before the carotid occlusion. Stroke index was measured during the reperfusion. ATPase activity, glutamate (Glu) and aspartate contents in brain tissue homogenate were examined. The results showed that catalpol significantly improved the stroke index compared with sham group (P < 0.05 or P < 0.01). Catalpol markedly increased the activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase (P < 0.05 or P < 0.01), and significantly decreased the content of Glu in brain tissue (P < 0.05 or P < 0.01). These data suggest that the efficacy of catalpol pretreatment on CI/R injury is associated with the enhancement of ATPase activity and the inhibition of excitatory amino acid toxicity.

Effects of resveratrol on apoptosis in a rat model of vascular dementia.

Resveratrol is a natural polyphenol widely present in plants, particularly in the skin of red grapes and in wine. It possesses a wide range of biological effects and exhibits neuroprotective effects in numerous diseases. However, data evaluating the effects of resveratrol in vascular dementia (VaD) are lacking. In the present study, the permanent, bilateral common carotid artery occlusion rat model was used to study the effects of resveratrol on VaD. The Morris water maze was used to test the spatial learning and memory performance of the rats. The expression levels of Bax, Bcl-2, cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) in the hippocampus were measured. The results showed that resveratrol inhibited memory impairment in the VaD rat model, and attenuated the increases in the expression levels of Bax, cleaved caspase-3 and cleaved PARP and the reductions in the expression levels of Bcl-2 that were induced by VaD. These results provide a novel insight into the neuroprotective effects of resveratrol and its possible therapeutic role in VaD.