Mechanistic insights on cytotoxicity of KOLR, Cinnamomum pauciflorum Nees leaf derived active ingredient, by targeting signaling complexes of phosphodiesterase 3B and rap guanine nucleotide exchange factor 3.

Protein signaling complexes play important roles in prevention of several cancer types and can be used for development of targeted therapy. The roles of signaling complexes of phosphodiesterase 3B (PDE3B) and Rap guanine nucleotide exchange factor 3 (RAPGEF3), which are two important enzymes of cyclic adenosine monophosphate (cAMP) metabolism, in cancer have not been fully explored. In the current study, a natural product Kaempferol-3-O-(3'',4''-di-E-p-coumaroyl)-α-L-rhamnopyranoside designated as KOLR was extracted from Cinnamomum pauciflorum Nees leaves. KOLR exhibited higher cytotoxic effects against BxCP-3 pancreatic cancer cell line. In BxPC-3 cells, the KOLR could enhance the formation of RAPGEF 3/ PDE3B protein complex to inhibit the activation of Rap-1 and PI3K-AKT pathway, thereby promoting cell apoptosis and inhibiting cell metastasis. Mutation of RAPGEF3 G557A or low expression of PDE3B inactivated the binding action of KOLR resulting in KOLR resistance. The findings of this study show that PDE3B/RAPGEF3 complex is a potential therapeutic cancer target.

Differential Metabolomics and Network Pharmacology Analysis of Silkworm Biotransformation between Mulberry Leaves and Silkworm Droppings.

Silkworm droppings are the product of mulberry leaves digested by silkworm intestines, which are an important medicinal resource in traditional Chinese medicine (TCM). The contents of total fat, fat acids, crude protein, amino acids, and secondary metabolites of obtained mulberry leaves and silkworm droppings were analyzed by HPLC, GC-MS, and UHPLC-Q-TOF MS. The target genes and enriched pathways related to significantly changed compositions between mulberry leaves and silkworm droppings were analyzed by network pharmacology. High unsaturated C18 : 3 fatty acids were transformed to low unsaturated C18 : 1 from mulberry leaves to silkworm droppings. Only lysine and 17 mini-peptides had significantly higher content in silkworm droppings than in mulberry leaves. There were 36 common target genes or the different compounds between mulberry leaves and silkworm droppings. The main pathways of mulberry leaf were enriched in antivirus and anticancer properties, while the pathways of silkworm droppings were enriched in hormone regulation and signal transduction.

The analgesic effect of early hyperbaric oxygen treatment in chronic constriction injury rats and its influence on nNOS and iNOS expression and inflammatory factor production.

Objective To observe the analgesic effect of early hyperbaric oxygen (HBO) treatment in chronic constriction injury (CCI) rats, and to analyze the influence of HBO on the expression of neuronal nitric oxide synthase and inducible nitric oxide synthase and on the levels of inflammatory factors. Methods Rats were assigned into three groups randomly: sham, CCI, and HBO groups. The CCI rat model was established, and HBO treatment at 2.5 ATA (60 min) was given one day after surgery, lasting for five consecutive days. The pain behaviors of the rats were observed at predetermined time points, and the activation of astrocytes at dorsal horns as well as the changes of the synaptic ultrastructures were observed. The expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were detected by Western blot, and the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) were detected by quantitative real-time PCR. Results Rats in the CCI group developed hyperalgesia when compared with the sham group. Mechanical withdrawal threshold decreased and thermal withdrawal latency shortened in CCI group. Also, astrocytes at the dorsal horn were activated, the synaptic structure was disordered, the expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were increased significantly, and the release of inflammatory factor (TNF-α and IL-1ß) was up-regulated. However, with early initiation of HBO treatment, rats in the HBO group showed significantly alleviated hyperalgesia, increased mechanical withdrawal threshold, and prolonged thermal withdrawal latency. HBO treatment inhibited astrocyte expression and maintained normal synaptic structure. The expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase were decreased in the dorsal horn, and the release of inflammatory factor (TNF-α and IL-1ß) was reduced. Conclusions Early HBO treatment significantly improves hyperalgesia in rats with neuropathic pain. The decreased expressions of inducible nitric oxide synthase and neuronal nitric oxide synthase and reduced levels of inflammatory factors are important mechanisms by which early HBO helps to alleviate neuropathic pain.

Study on the inhibition of Mfn1 by plant-derived miR5338 mediating the treatment of BPH with rape bee pollen.

BACKGROUND: Recent studies have found that plant derived microRNA can cross-kingdom regulate the expression of genes in humans and other mammals, thereby resisting diseases. Can exogenous miRNAs cross the blood-prostate barrier and entry prostate then participate in prostate disease treatment? METHODS: Using HiSeq sequencing and RT-qPCR technology, we detected plant miRNAs that enriched in the prostates of rats among the normal group, BPH model group and rape bee pollen group. To forecast the functions of these miRNAs, the psRobot software and TargetFinder software were used to predict their candidate target genes in rat genome. The qRT-PCR technology was used to validate the expression of candidate target genes. RESULTS: Plant miR5338 was enriched in the posterior lobes of prostate gland of rats fed with rape bee pollen, which was accompanied by the improvement of BPH. Among the predicted target genes of miR5338, Mfn1 was significantly lower in posterior lobes of prostates of rats in the rape bee pollen group than control groups. Further experiments suggested that Mfn1 was highly related to BPH. CONCLUSIONS: These results suggesting that plant-derived miR5338 may involve in treatment of rat BPH through inhibiting Mfn1 in prostate. These results will provide more evidence for plant miRNAs cross-kingdom regulation of animal gene, and will provide preliminary theoretical and experimental basis for development of rape bee pollen into innovative health care product or medicine for the treatment of BPH.

Honeysuckle flowers extract loaded Bombyx mori silk fibroin films for inducing apoptosis of HeLa cells.

This study aimed to prepare silk fibroin (SF) films loaded with honeysuckle flowers extract (HFE) for inducing apoptosis of HeLa cells. We mixed solution of SF and HFE by air-drying for preparing the honeysuckle flowers extract loaded silk fibroin (SFH) films. The physical properties including morphologies, contact angle, roughness, and Z range were characterized. MTS assay and fluorescence micrographs proved that SFH films inhibited the proliferation rate of HeLa cells due to induction of HFE into SF films. Furthermore, cell apoptosis assay and cell cycle analysis confirmed that the apoptosis of HeLa cells resulted from SFH films. Therefore, SFH films designed in our study might be a promising candidate material for cancer therapy.

Identification of Dietetically Absorbed Rapeseed (Brassica campestris L.) Bee Pollen MicroRNAs in Serum of Mice.

MicroRNAs (miRNAs) are a class of small noncoding RNA that, through mediating posttranscriptional gene regulation, play a critical role in nearly all biological processes. Over the last decade it has become apparent that plant miRNAs may serve as a novel functional component of food with therapeutic effects including anti-influenza and antitumor. Rapeseed bee pollen has good properties in enhancing immune function as well as preventing and treating disease. In this study, we identified the exogenous miRNAs from rapeseed bee pollen in mice blood using RNA-seq technology. We found that miR-166a was the most highly enriched exogenous plant miRNAs in the blood of mice fed with rapeseed bee pollen, followed by miR-159. Subsequently, RT-qPCR results confirmed that these two miRNAs also can be detected in rapeseed bee pollen. Our results suggested that food-derived exogenous miRNAs from rapeseed bee pollen could be absorbed in mice and the abundance of exogenous miRNAs in mouse blood is dependent on their original levels in the rapeseed bee pollen.

[Study on treatment of iron-deficiency anemia by shengxuening].

OBJECTIVE: To observe the therapeutic effect of shengxuening (SXN) in treating iron-deficiency anemia (IDA) and to explore its molecular mechanism on iron metabolism balance regulation. METHODS: Patients with IDA were randomly divided into the treated group and the control group, 50 in each group. They were treated with SXN (0.1 g, three times per day) and ferrous gluconate (0.1 g, three times per day) respectively, for 30 days. Levels of serum iron (Fe), total iron binding capacity (TIBC), transferrin saturation (TS), serum ferritin (SF), transferrin (Tf), soluble transferrin receptor (sTfR) and blood routine test, as well as scoring of TCM qi-blood deficiency Syndrome were conducted before and after treatment. RESULTS: The total effective rate in the treated group reached 92%, it was shown that SXN could improve the iron metabolism, increase levels of Fe, TS, SF and reduce levels of TIBC, Tf, sTfR, it has obvious effect in promoting erythrocyte generation and could promote formation of leucocytes and platelets. The total effective rate in the control group was 32%, which was significantly lower than that in the treated group (P < 0.01). CONCLUSION: The effect of SXN in treating IDA and qi-blood deficiency Syndrome is evident, it could improve the iron metabolism, increase levels of Fe, TS, SF and lower levels of TIBC, Tf, sTfR.