Assessment of the Effect of Leonurine Hydrochloride in a Mouse Model of PCOS by Gene Expression Profiling.

Polycystic ovary syndrome (PCOS) is an endocrine disease commonly associated with metabolic disorders in females. Leonurine hydrochloride (Leo) plays an important role in regulating immunity, tumours, uterine smooth muscle, and ovarian function. However, the effect of Leo on PCOS has not been reported. Here, we used dehydroepiandrosterone to establish a mouse model of PCOS, and some mice were then treated with Leo by gavage. We found that Leo could improve the irregular oestros cycle of PCOS mice, reverse the significantly greater serum testosterone (T) and luteinising hormone (LH) levels, significantly reduce the follicle-stimulating hormone (FSH) level, and significantly increase the LH/FSH ratio of PCOS mice. Leo could also change the phenomenon of ovaries in PCOS mice presented with cystic follicular multiplication and a lacking corpus luteum. Transcriptome analysis identified 177 differentially expressed genes related to follicular development between the model and Leo groups. Notably, the cAMP signalling pathway, neuroactive ligand-receptor interactions, the calcium signalling pathway, the ovarian steroidogenesis pathway, and the Lhcgr, Star, Cyp11a, Hsd17b7, Camk2b, Calml4, and Phkg1 genes may be most related to improvements in hormone levels and the numbers of ovarian cystic follicles and corpora lutea in PCOS mice treated by Leo, which provides a reference for further study of the mechanism of Leo.

The combination of graphene oxide and preservatives can further improve the preservation of cut flowers.

It is reported that the use of nanomaterials can extend the vase life of fresh-cut flowers. Graphene oxide (GO) is one of these nanomaterials that aid in promoting water absorption and antioxidation during the preservation of fresh-cut flowers. In this investigation, the three mainstream brands of preservatives commercially available on the market ("Chrysal," "Floralife," and "Long Life") in combination with low concentrations of GO (0.15 mg/L) were used to preserve fresh-cut roses. The results showed that the three brands of preservatives had different degrees of freshness retention. Compared to the preservatives used alone, the combination of low concentrations of GO with the preservatives, especially in the L+GO group (with 0.15 mg/L GO added in the preservative solution of "Long life"), further improved the preservation of cut flowers. L+GO group showed less level of antioxidant enzyme activities, lower ROS accumulation and cell death rate, and higher relative fresh weight than the other groups, implying a better antioxidant and water balance abilities. GO attached to the xylem duct of flower stem, and reduced the blockage of xylem vessels by bacteria, which were determined by SEM (scanning electron microscopy) and FTIR (Fourier transform infrared) analysis. XPS (X-ray photoenergy spectra) analysis results proved that GO could enter the interior of flower stem through xylem duct, and when combined with "Long Life," the anti-oxidation protection ability of GO was enhanced, thus delaying ageing, and greatly extending the vase life of fresh-cut flowers. The study provides new insights into cut flower preservation using GO.

Silencing IQGAP1 alleviates hepatic fibrogenesis via blocking bone marrow mesenchymal stromal cell recruitment to fibrotic liver.

IQ motif-containing guanosine triphosphatase (GTPase)-activating protein 1 (IQGAP1) is a cytosolic scaffolding protein involved in cell migration. Our previous studies suggest sphingosine 1-phosphate (S1P) triggers bone marrow (BM) mesenchymal stromal cells (BMSCs) to damaged liver, thereby promoting liver fibrosis. However, the role of IQGAP1 in S1P-induced BMSC migration and liver fibrogenesis remains unclear. Chimeric mice of BM cell labeled by EGFP were used to build methionine-choline-deficient and high-fat (MCDHF)-diet-induced mouse liver fibrosis. IQGAP1 small interfering RNA (siRNA) was utilized to silence IQGAP1 in vivo. IQGAP1 expression is significantly elevated in MCDHF-diet-induced mouse fibrotic livers. Positive correlations are presented between IQGAP1 and fibrosis hallmarks expressions in human and mouse fibrotic livers. In vitro, depressing IQGAP1 expression blocks S1P-induced motility and cytoskeleton remodeling of BMSCs. S1P facilitates IQGAP1 aggregating to plasma membrane via S1P receptor 3 (S1PR3) and Cdc42/Rac1. In addition, IQGAP1 binds to Cdc42/Rac1, regulating S1P-induced activation of Cdc42/Rac1 and mediating BMSC migration in concert. In vivo, silencing IQGAP1 reduces the recruitment of BMSCs to impaired liver and effectively alleviates liver fibrosis induced by MCDHF diet. Together, silencing IQGAP1 relieves liver fibrosis by blocking BMSC migration, providing an effective therapeutic strategy for liver fibrosis.

Doxorubicin-loaded folate-mediated pH-responsive micelle based on Bletilla striata polysaccharide: Release mechanism, cellular uptake mechanism, distribution, pharmacokinetics, and antitumor effects.

This study evaluated the potential of folate (FA)-mediated and stearic acid (SA) modified Bletilla striata polysaccharide (FA-BSP-SA) copolymer as the vehicle for targeted delivery of anticancer drugs to tumor tissues and enhanced antitumor efficacy. The critical aggregation concentration, morphology, particle size, and zeta potential of micelles were increased with the reduction of pH values. The complex between doxorubicin (Dox) hydrochloride and sodium cholate via electrostatic interaction was fabricated and then directly encapsulated into FA-BSP-SA micelles. Dox in micelles existed in the status of amorphism. The Dox/FA-BSP-SA micelles demonstrated pH-responsive release behavior under the combination of diffusion and erosion mechanism. They could clearly strengthen the cellular uptake of Dox and inhibit the proliferation and the migration of tumor cells compared with the Dox/BSP-SA micelles and the free Dox. The Dox/FA-BSP-SA micelles were further delivered to lysosomes, mainly due to clathrin-mediated endocytosis. The FA-BSP-SA micelles distinctly improved the absolute bioavailability of Dox compared with the free Dox and the Dox/BSP-SA micelles (p < 0.01) and prolong the mean residence time. The Dox/FA-BSP-SA micelles significantly increased the drug enrichment in the tumor sites and enhanced the antitumor effects in vivo. Taken together, the FA-BSP-SA micelle could be exploited as a potential platform for targeting anticancer drug delivery.

The roles of GRP81 as a metabolic sensor and inflammatory mediator.

GPR81 (also named as HCA1) is a member of a subfamily of orphan G-protein coupled receptors (GPCRs), coupled to Gi -type G proteins. GPR81 was discovered in 2001 and identified as the only known endogenous receptor of lactate under physiological conditions in 2008, which opened a new field of research on how lactate may act as a signal molecule along with the GPR81 expression in the roles of metabolic process and inflammatory response. Recent studies showed that the physiological functions of GPR81 include lipid metabolism in adipose tissues, metabolic excitability in the brain, cellular development, and inflammatory response modulation. These findings may reveal a novel therapeutic strategy to treat clinical, metabolic, and inflammatory diseases. This article will summarize past research on GPR81, including its characteristics of distribution and expression, functional residues, pharmacological, and physiological agonists, involvement in signal transduction, and pharmacological applications.

Synergistic effects of antitumor efficacy via mixed nano-size micelles of multifunctional Bletilla striata polysaccharide-based copolymer and D-α-tocopheryl polyethylene glycol succinate.

To evaluate if mixed micelles of Dox@FA-BSP-SA/TPGS can allow for the superior antitumor efficiency than Dox@FA-BSP-SA micelles. The complex of doxorubicin (Dox) and sodium cholate was encapsulated into the mixed micelles composed of folate-mediated stearic acid-modified Bletilla striata polysaccharide (FA-BSP-SA) and D-α-tocopheryl polyethylene glycol succinate (TPGS). Its average particle size increased whereas load capacity (LC) and encapsulation efficiency (EE) decreased with the increase of TPGS mass ratio in the mixed micelles. The changes of morphology, particle size and doxorubicin release in vitro demonstrated the pH sensitivity of micelles. FA-BSP-SA/TPGS mixed micelle exhibited average particle size of 147.3 nm, LC of 14.4% and EE of 91.9% for doxorubicin at the weight ratio of 3: 1. The doxorubicin release rate of micelles was faster in pH 5.0 media compared with that in pH 6.0 and 7.4 media. The cytotoxicity in vitro and antitumor efficacy in vivo results of Dox@FA-BSP-SA/TPGS micelle were more superior to that of free doxorubicin and Dox@FA-BSP-SA single micelle. For Dox@FA-BSP-SA/TPGS micelle, the clathrin-mediated endocytosis was the dominant mechanism of intracellular uptake. The FA-BSP-SA/TPGS mixed micelle may be a promising drug delivery system for cancer chemotherapy.

Bio-responsive Bletilla striata polysaccharide-based micelles for enhancing intracellular docetaxel delivery.

The aim of this study was to design a pH- and redox-dual responsive Bletilla striata polysaccharide (BSP)-based copolymer to enhance anti-tumor drugs release at tumor sites and improve the therapeutic effect. The copolymer was synthesized using stearic acid (SA) and cystamine via a disulfide linkage and characterized using 1H-Nuclear Magnetic Resonance spectroscopy and Fourier Transform Infrared spectroscopy. The BSP-ss-SA copolymer could self-assemble into micelle in an aqueous environment and could encapsulate docetaxel therein. Its inhibitory effects on HepG2 cells and 4 T1 cells were determined. Besides, the anti-cancer effects in vivo and histopathological study of 4 T1-bearing tumor mice were also evaluated. Docetaxel-loaded BSP-ss-SA micelles showed significant pH-sensitive release behavior, supplying a greater drug release percentage in pH 5.0 media compared to pH 7.4 media. BSP-ss-SA micelles exhibited a clear redox-responsive release property in pH 7.4 media whereas the similar cumulative release percentage of docetaxel from BSP-ss-SA micelles in pH 5.0 media in the presence and absence of DL-dithiothreitol. The Docetaxel-loaded BSP-ss-SA micelles clearly inhibited the proliferation of HepG2 and 4 T1 cells compared with docetaxel solution. The results of MTT and histopathological study indicated that BSP-ss-SA copolymer exhibited good blood compatibility. The BSP-ss-SA copolymer may be used as carriers to deliver anti-tumor drugs to special tumor tissues.

Sphingosine 1-Phosphate Receptor Blockade Affects Pro-Inflammatory Bone Marrow-Derived Macrophages and Relieves Mouse Fatty Liver Injury.

Fatty liver injury is characterized by liver fat accumulation and results in serious health problems worldwide. There is no effective treatment that reverses fatty liver injury besides etiological therapy. Inflammation is an important macrophage-involving pathological process of liver injury. Here, we investigated the role of sphingosine 1-phosphate receptors (S1PRs) in fatty liver injury and explored whether S1PR2/3 blockade could cure fatty liver injury. A methionine-choline-deficient and a high-fat (MCDHF) diet was used to induce fatty liver injury, and the number of macrophages was evaluated by flow cytometry. Gene expressions were detected using RT-qPCR and cytometric bead array. In MCDHF-diet-fed mice, pro-inflammatory factor expressions were upregulated by fatty liver injury. The S1P level and S1PR2/3 expressions were significantly elevated. Moreover, increased S1P level and S1PR2/3 mRNA expressions were positively correlated with pro-inflammatory factor expressions in the liver. Furthermore, the number of pro-inflammatory macrophages (iMφ) increased in injured liver, and they were mainly bone-marrow-derived macrophages. In vivo, S1PR2/3 blockade decreased the amount of iMφ and inflammation and attenuated liver injury and fibrosis, although liver fat accumulation was unchanged. These data strongly suggest that anti-inflammatory treatment by blocking the S1P/S1PR2/3 axis attenuates fatty liver injury, which might serve as a potential target for fatty liver injury.

Aerobic Exercise Improves Synaptic-Related Proteins of Diabetic Rats by Inhibiting FOXO1/NF-κB/NLRP3 Inflammatory Signaling Pathway and Ameliorating PI3K/Akt Insulin Signaling Pathway.

Diabetes mellitus is metabolic syndrome and a risk factor for cognitive dysfunction-related diseases such as dementia, especially Alzheimer's disease (AD), which is associated with chronic inflammation and abnormal insulin signaling pathway. Exercise, a known potential therapy for diabetes, can also alleviate neurodegeneration. We evaluated the effects of aerobic exercise on inflammation and insulin signaling pathway in the prefrontal cortex of diabetic rats. Male SD rats were fed with a normal diet or a high-fat diet (HFD) for 8 weeks. Then, part of the HFD rats was selected for aerobic exercise training. Our results show that aerobic exercise can improve the expression of synaptic plasticity-related proteins and reduce the phosphorylation of Tau by inhibiting the inflammatory signaling pathway and ameliorating the insulin signaling pathway in diabetic rats.

Mechanisms of Aerobic Exercise Upregulating the Expression of Hippocampal Synaptic Plasticity-Associated Proteins in Diabetic Rats.

We investigated the effects of aerobic exercise on the expression of hippocampal synaptic plasticity-associated proteins in rats with type 2 diabetes and their possible mechanisms. A type 2 diabetes rat model was established with 8 weeks of high-fat diet combined with a single intraperitoneal injection of streptozotocin (STZ). Then, a 4-week aerobic exercise intervention was conducted. Memory performance was measured with Y maze tests. The expression and activity of synaptic plasticity-associated proteins and of proteins involved in the PI3K/Akt/mTOR, AMPK/Sirt1, and NFκB/NLRP3/IL-1ß signaling pathways were evaluated by western blot. Our results show that aerobic exercise promotes the expression of synaptic plasticity-associated proteins in the hippocampus of diabetic rats. Aerobic exercise also activates the PI3K/Akt/mTOR and AMPK/Sirt1 signaling pathways and inhibits the NFκB/NLRP3/IL-1ß signaling pathway in the hippocampus of diabetic rats. Therefore, modulating the PI3K/Akt/mTOR, AMPK/Sirt1, and NFκB/NLRP3/IL-1ß signaling pathways is probably the mechanism of aerobic exercise upregulating the expression of hippocampal synaptic plasticity-associated proteins in diabetic rats.

Interactions of Self-Assembled Bletilla Striata Polysaccharide Nanoparticles with Bovine Serum Albumin and Biodistribution of Its Docetaxel-Loaded Nanoparticles.

: Amphiphilic copolymers of stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs-SA) with three different degrees of substitution (DSs) were synthesized. The effects of DS values on the properties of BSPs-SA nanoparticles were evaluated. Drug state, cytotoxicity, and histological studies were carried out. The affinity ability of bovine serum albumin (BSA) and the BSPs-SA nanoparticles was also characterized utilizing ultraviolet and fluorescence spectroscopy. Besides, the bioavailability and tissue distribution of docetaxel (DTX)-loaded BSPs-SA nanoparticles were also assessed. The results demonstrated that the DS increase of the hydrophobic stearic acid segment increased the negative charge, encapsulation efficiency, and drug-loading capacity while decreasing the critical aggregation concentration value as well as the release rate of docetaxel from the nanoparticles. Docetaxel was encapsulated in nanoparticles at the small molecules or had an amorphous status. The inhibitory capability of DTX-loaded BSPs-SA nanoparticles against 4T1 tumor cells was superior to that of Duopafei®. The ultraviolet and fluorescence results exhibited a strong binding affinity between BSPs-SA nanoparticles and bovine serum albumin, but the conformation of bovine serum albumin was not altered. Additionally, the area under the concentration⁻time curve (AUC0⁻∞) of DTX-loaded BSPs-SA nanoparticles was about 1.42-fold higher compared with Duopafei® in tumor-bearing mice. Docetaxel levels of DTX-loaded BSPs-SA nanoparticles in some organs changed, and more docetaxel accumulated in the liver, spleen, and the tumor compared with Duopafei®. The experimental results provided a theoretical guidance for further applications of BSPs-SA conjugates as nanocarriers for delivering anticancer drugs.

Bidirectional chaos communication between two outer semiconductor lasers coupled mutually with a central semiconductor laser.

Based on a linear chain composed of a central semiconductor laser and two outer semiconductor lasers, chaos synchronization and bidirectional communication between two outer lasers have been investigated under the case that the central laser and the two outer lasers are coupled mutually, whereas there exists no coupling between the two outer lasers. The simulation results show that high-quality and stable isochronal synchronization between the two outer lasers can be achieved, while the cross-correlation coefficients between the two outer lasers and the central laser are very low under proper operation condition. Based on the high performance chaos synchronization between the two outer lasers, message bidirectional transmissions of bit rates up to 20 Gbit/s can be realized through adopting a novel decoding scheme which is different from that based on chaos pass filtering effect. Furthermore, the security of bidirectional communication is also analyzed.