Hypoglycemic effects of mountain caviar extract and inhibitory mechanism of saponins, including momordin Ic, on glucose absorption.

Mountain caviar is a fruit of Kochia scoparia that contains momordin Ic as a major saponin constituent. Its extract (MCE) has been shown to suppress blood glucose elevations in the human oral glucose tolerance test (OGTT) as well as increases in blood glucose in OGTT, gastric emptying (GE), and glucose incorporation in the small intestine in rats. However, the effects of MCE and momordin Ic on glucose absorption in mice and these action mechanisms have not been examined for more than 2 decades. Therefore, we herein investigated the effects of MCE, its saponin fraction, and momordin Ic on blood glucose elevations in mice. Mouse blood glucose elevation tests were performed on carbohydrate-loaded mice. The mountain caviar saponin fraction significantly delayed blood glucose elevations in glucose-, sucrose-, and soluble starch-loaded mice. In glucose-loaded mice, the saponin fraction, MCE, and momordin Ic significantly suppressed rapid glucose elevations after glucose loading, but not sucrose loading. A mouse GE study was performed by loading with glucose and phenolphthalein solution. Momordin Ic and MCE strongly suppressed mouse GE. Intestinal glucose absorption was evaluated by the incorporation of 2-deoxyglucose (2-DG) into Caco-2 cell layers and mouse duodenum wall vesicles. The results obtained showed that momordin Ic inhibited the incorporation of 2-DG into Caco-2 cells and mouse duodenum vesicles. Collectively, these results suggest that MCE, particularly the principal saponin, momordin Ic, preferably suppressed glucose-induced blood glucose elevations and delayed carbohydrate-induced glucose elevations in mice. The underlying mechanism was found to involve the suppression of GE and intestinal glucose absorption.

Atomically precise Au nanocluster-embedded carrageenan for single near-infrared light-triggered photothermal and photodynamic antibacterial therapy.

In this study, we report atomically precise gold nanoclusters-embedded natural polysaccharide carrageenan as a novel hydrogel platform for single near-infrared light-triggered photothermal (PTT) and photodynamic (PDT) antibacterial therapy. Briefly, atomically precise captopril-capped Au nanoclusters (Au25Capt18) prepared by an alkaline NaBH4 reduction method and then embedded them into the biosafe carrageenan to achieve superior PTT and PDT dual-mode antibacterial effect. In this platform, the embedded Au25Capt18, as simple-component phototherapeutic agents, exhibit superior thermal effects and singlet oxygen generation under a single near-infrared (NIR, 808 nm) light irradiation, which enables rapid elimination of bacteria. Carrageenan endows the hydrogel platform with superior gelation characteristics and wound microenvironmental regulation. The Au25Capt18-embedded hydrogels exhibited good water retention, hemostasis, and breathability, providing a favorable niche environment for promoting wound healing. In vitro experiments confirmed the excellent antibacterial activity of the Au25Capt18 hydrogels against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The antibacterial effect and promoting wound healing function were further validated in a S. aureus-infected wound model. Biosafety evaluation showed that the Au25Capt18 hydrogel has excellent biocompatibility. This PTT/PDT dual-mode therapy offers an alternative strategy for battling bacterial infections without antibiotics. More importantly, this hydrogel is facile to prepare which is helpful for expanding applications.

Edible Pueraria lobata-Derived Exosomes Promote M2 Macrophage Polarization.

Pueraria lobata (known as Gegen) is an edible and medicinal herb that is a nutritious medicine food homology plant in China. Previous studies indicated that P. lobata plays an essential role in controlling cytokines. However, the exact mechanism of the inflammation response is still unknown. In this study, we observed the uptake of P. lobata-derived exosomes (Exos) in isolated mouse macrophages. Our results show that P. lobata-derived Exos shift M1 macrophages toward the M2. These data present that P. lobata and puerarin might exert and enhance anti-inflammatory effects through the activation of exosomes and shifts in macrophage polarization, providing strong evidence for the application of P. lobata as novel an anti-inflammatory therapeutic biomaterial.

Statin-Induced Geranylgeranyl Pyrophosphate Depletion Promotes PCSK9-Dependent Adipose Insulin Resistance.

Statin treatment is accepted to prevent adverse cardiovascular events. However, statin therapy has been reported to be dose-dependently associated with increased risk for new-onset type 2 diabetes mellitus (T2DM). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is expressed in adipose tissue and is positively correlated with lipid metabolism. It is, however, unknown if PCSK9 participates in adipocyte insulin resistance occurring as a result of statin use. Our goal was to use an in vitro adipose tissue explant approach to support the hypothesis that PCSK9 regulates statin-induced new-onset T2DM. Studies were performed using Pcsk-/- and C57Bl/6J control mice. Pcsk9-/- and control mice were fed a high-fat diet to affect a state of chronically altered lipid metabolism and increased PCSK9. Epididymal fat was excised and incubated with atorvastatin (1 µmol/L) in the absence and presence of insulin or geranylgeranyl pyrophosphate (GGPP). PCSK9 mRNA was evaluated using quantitative rtPCR. We further examined the effects of atorvastatin on insulin-mediated AKT signaling in adipose tissue explants by immunoblotting. Atorvastatin was found to upregulate PCSK9 gene expression in adipose tissue. The metabolic intermediate GGPP is required to downregulate PCSK9 expression. PCSK9 deficiency protects against statin-induced impairments in insulin signaling. Moreover, supplementation with GGPP reversed atorvastatin-induced suppression of insulin signaling. Furthermore, the basal and atorvastatin-stimulated release of free fatty acids was observed in adipose tissue from wild-type mice but not PCSK9 deficient mice. Collectively, we describe a novel mechanism for PCSK9 expression in adipose tissue that could mediate statin-impaired adipose insulin resistance.

Statin-Induced Geranylgeranyl Pyrophosphate Depletion Promotes Ferroptosis-Related Senescence in Adipose Tissue.

Statin treatment is accepted to prevent adverse cardiovascular events. However, atorvastatin, an HMG-CoA reductase inhibitor, has been reported to exhibit distinct effects on senescent phenotypes. Whether atorvastatin can induce adipose tissue senescence and the mechanisms involved are unknown. The effects of atorvastatin-induced senescence were examined in mouse adipose tissue explants. Here, we showed that statin initiated higher levels of mRNA related to cellular senescence markers and senescence-associated secretory phenotype (SASP), as well as increased accumulation of the senescence-associated ß-galactosidase (SA-ß-gal) stain in adipose tissues. Furthermore, we found that the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+ were elevated in adipose tissues treated with atorvastatin, accompanied by a decrease in the expression of glutathione (GSH), and glutathione peroxidase 4 (GPX4), indicating an iron-dependent ferroptosis. Atorvastatin-induced was prevented by a selective ferroptosis inhibitor (Fer-1). Moreover, supplementation with geranylgeranyl pyrophosphate (GGPP), a metabolic intermediate, reversed atorvastatin-induced senescence, SASP, and lipid peroxidation in adipose tissue explants. Atorvastatin depleted GGPP production, but not Fer-1. Atorvastatin was able to induce ferroptosis in adipose tissue, which was due to increased ROS and an increase in cellular senescence. Moreover, this effect could be reversed by the supplement of GGPP. Taken together, our results suggest that the induction of ferroptosis contributed to statin-induced cell senescence in adipose tissue.

The Astragaloside IV Derivative LS-102 Ameliorates Obesity-Related Nephropathy.

Background: Astragaloside IV is the most important bioactive component of Radix Astragali. Previous studies have shown that astragaloside IV plays an important role in the control of early- and mid-stage diabetes and late diabetic nephropathy. However, it is disappointing that the in vivo solubility of astragaloside IV and its bioavailability after oral administration are very low. We recently obtained a new water-soluble derivative of astragaloside IV-astragaloside formic acid (LS-102), which has higher bioavailability than the parent compound. In our previous study, we found that there was a significant inflammatory response in the perirenal adipose tissue of mice with obesity-related nephropathy induced by a high-fat diet (HFD), which was related to macrophage infiltration. We hypothesized that in model mice with obesity-related nephropathy, LS-102 effectively regulated the inflammatory response and pathological changes in obesity-related nephropathy through macrophages in perirenal adipose tissue. If this hypothesis is true, the effects of LS-102 and astragaloside IV on TGF-ß1/Smad signal transduction will be further investigated. Methods: In this study, adipose stem cells and an HFD-induced obesity-related nephropathy mouse model were used to observe the regulatory effect of LS-102 on perirenal fat inflammation and the mechanism. Adipose mesenchymal stem cells were extracted from mice that were fed a normal diet and those with obesity-related nephropathy. The effects of LS-102 on the proliferation of two kinds of cells were measured by the CCK-8 method. The levels of tumor necrosis factor-α (TNF-a) and plasminogen activator inhibitor-1 (PAI-1) were measured by ELISA. Obesity-related nephropathy mice were randomly divided into five groups: the HFD group, the LAS group (HFD+low concentration of astragaloside IV [10 mg/kg], intragastrically [ig]), the HAS group (HFD+high concentration of astragaloside IV [40 mg/kg], ig), the L102 group (HFD+low concentration of LS-102 [10 mg/kg], ig) and the H102 group (HFD+high concentration of LS-102 [40 mg/kg], ig). Body weight was measured, and the levels of serum glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), serum creatinine (Crea) and blood urea were measured. The kidneys were stained with HE, PAS and Masson's trichrome. Perirenal adipose tissue was harvested to examine the expression of CD68, LCA, CD11C, TNF-a, TGF-ß1, Fn1, Smad2, Smad3, Smad4, and Smad7 by immunohistochemical staining, and F4/80 was examined by immunofluorescence staining. Results: LS-102 significantly inhibited the in vitro secretion of TNF-a and PAI-1 by adipose stem cells in a concentration-dependent manner (P < 0.05). In vivo, the body weights in the LAS group, HAS group, L102 group and H102 group were significantly lower than those in the HFD group (P < 0.05). Except for that in the HFD group, the volume of perirenal adipocytes in the other groups was small and uniform (P < 0.05). Compared with the LAS, HAS, L102 and H102 groups, the HFD group had a larger glomerular cross-sectional area, proliferation of mesangial cells and the mesangial matrix, and increased matrix area/glomerular area (P < 0.05). The effect of LS-102 was better than that of astragaloside IV at the same concentration (P < 0.05). Compared with those in the HFD group, glucose, HDL-C, LDL-C and urea levels in the LAS group, HAS group, L102 group and H102 group were significantly decreased (P < 0.05). The expression of F4/80, CD68, LCA, TNF-a, CD11C, and PAI-1 in perirenal adipose tissue in the HFD group was significantly higher than that in the LAS group, HAS group, L102 group and H102 group (P < 0.05). Compared with those in the HFD group, the expression levels of TGF-ß1 and Fn1 in the HAS group, L102 group and H102 group were significantly increased (P < 0.05). Compared with the HFD group, the HAS group, L102 group and H102 group had decreased immunopositive rates of Smad2, Smad3 and Smad4 (P < 0.05). At the same concentration, the effect of LS-102 was better than that of astragaloside IV (P < 0.05). There was no significant difference in the expression of Smad7 among the different experimental groups (P > 0.05). Conclusion: Astragaloside IV and LS-102 improved the inflammatory reaction in perirenal adipose tissue and renal pathological changes in obesity-related nephropathy model mice and inhibited the TGF-ß1/Smad signaling cascade. At the same concentration, the effect of LS-102 was better than that of astragaloside IV. These results suggest that LS-102 has a better protective effect against obesity-related nephropathy. LS-102 may be a new type of traditional Chinese medicine for the clinical treatment of obesity and its related metabolic diseases.

The Anti-Adiposity Mechanisms of Ampelopsin and Vine Tea Extract in High Fat Diet and Alcohol-Induced Fatty Liver Mouse Models.

Ampelopsis grossedentata (AG) is an ancient medicinal plant that is mainly distributed and used in southwest China. It exerts therapeutic effects, such as antioxidant, anti-diabetic, and anti-inflammatory activities, reductions in blood pressure and cholesterol and hepatoprotective effects. Researchers in China recently reported the anti-obesity effects of AG extract in diet-induced obese mice and rats. To verify these findings, we herein investigated the effects of AG extract and its principal compound, ampelopsin, in high-fat diet (HFD)- and alcohol diet-fed mice, olive oil-loaded mice, and differentiated 3T3-L1 cells. The results obtained showed that AG extract and ampelopsin significantly suppressed increases in the weights of body, livers and abdominal fat and also up-regulated the expression of carnitine palmitoyltransferase 1A in HFD-fed mice. In olive oil-loaded mice, AG extract and ampelopsin significantly attenuated increases in serum triglyceride (TG) levels. In differentiated 3T3-L1 cells, AG extract and ampelopsin promoted TG decomposition, which appeared to be attributed to the expression of hormone-sensitive lipase. In alcohol diet-fed mice, AG extract and ampelopsin reduced serum levels of ethanol, glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) and liver TG. An examination of metabolic enzyme expression patterns revealed that AG extract and ampelopsin mainly enhanced the expression of aldehyde dehydrogenase and suppressed that of cytochrome P450, family 2, subfamily e1. In conclusion, AG extract and ampelopsin suppressed diet-induced intestinal fat accumulation and reduced the risk of fatty liver associated with HFD and alcohol consumption.

Different susceptibility of spores and hyphae of Trichophyton rubrum to methylene blue mediated photodynamic treatment in vitro.

BACKGROUND: In recent years, methylene blue mediated-photodynamic therapy (MB-PDT) has proved to be an effective inhibitor to a variety of microorganisms, including Trichophyton rubrum, the most common dermatophyte worldwide. However, previous studies mainly focused on the spore form of T rubrum, but rarely on its hyphal form, although the latter is the main pathogenic form of T rubrum in vivo. OBJECTIVE: To investigate the inhibitory effect of MB-PDT on T rubrum in different growth phases in vitro. METHODS: The suspensions of spores and hyphae obtained from T rubrum (ATCC28188) were prepared, respectively, incubated with MB solution (0.15-40 µg/mL) and irradiated with 635 nm red light. Varied light energy and MB concentration were used. The specimen in the absence of light exposure or/and MB served as controls. MIC determination, colony counts and MTT assay were employed to evaluate the antifungal effect of MB-PDT. RESULTS: The MICs of MB-PDT for hyphae and spores of T. rubrum were 6.300 ± 1.072 µg/mL and 1.984 ± 1.072 µg/mL, respectively, at a fixed light dose of 60 J/cm2 . CFU counts gave the minimum critical combinations of MB concentration and light dose to achieve 100% inhibitory rate. For hyphae, they were 5 µg/mL + 100 J/cm2 or 10 µg/mL + 60 J/cm2 . For spores, they were 1.25 µg/mL + 40 J/cm2 or 5 µg/mL + 20 J/cm2 . The outcomes of MTT assay were consistent with those of CFU counts, but less accurate. CONCLUSION: MB-PDT is a potent inhibitor to both spores and hyphae of T. rubrum in vitro, and the spores are more sensitive to it. Its antifungal efficacy is positively correlated with the concentration of MB and light dose.

Effects of Sanoshashinto on left ventricular hypertrophy and gut microbiota in spontaneously hypertensive rats.

In our previous study, we found that the methanolic extract of Sanoshashinto () (SHXXTM) exhibited significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine were the main antihypertensive constituents in SHXXTM. We also speculated that the baicalin-berberine (BB) combination produced vasorelaxant effects by activating the NO/cGMP pathway, and the BKCa channel and the DAG/PKC/CPI-17 pathway were involved. In this study, we examined the vasorelaxant effects using helical strips of rat aorta pretreated with different activators or inhibitors. The results suggested that the KATP channel and the voltage-dependent Ca2+ channel (VDCC) were also involved in the vasorelaxant effects. Furthermore, we found that SHXXTM and the BB combination reduced left ventricular hypertrophy and altered gut microbiota. Together, the results indicated that Sanoshashinto might have comprehensive effects on ameliorating hypertension.

Antihypertensive constituents in Sanoshashinto.

It has been reported that Sanoshashinto (SanHuangXieXinTang, ), which is composed of Rhei Rhizoma, Scutellariae Radix, and Coptidis Rhizoma, exhibits vasorelaxant effects in vitro and lowers blood pressure of patients. Based on this discovery, in this study, a mixture containing those three materials and combinations of them were extracted with methanol, and the extracts were fractionated into different parts. Effects of all extracts and fractions on high concentration of potassium chloride (High K+)- or noradrenaline (NA)-induced contractions of isolated rat aortic rings or helical strips were examined. Qualitative and quantitative HPLC analyses of the extracts and the fractions revealed that the contents of baicalin and berberine in Sanoshashinto methanol extract (SHXXTM) were higher than those of the other constituents. All pharmacological and HPLC data were analyzed by principal component analysis (PCA) software and the results indicated that baicalin, berberine, palmatine, baicalein, and wogonoside contributed significantly to the pharmacological activity. Furthermore, spontaneously hypertensive rats (SHRs) that were orally given SHXXTM or a baicalin-berberine combination showed significantly reduced increase in the rate of systolic blood pressure (SBP) compared to the control group. These findings suggested that Sanoshashinto has significant vasorelaxant effects in vitro and antihypertensive effects in vivo, and baicalin and berberine, which were the principal constituents of Scutellariae Radix and Coptidis Rhizoma, were the main antihypertensive constituents in Sanoshashinto. It was speculated that baicalin and berberine produced vasorelaxant effects by activating the NO/cGMP pathway and that the BKCa channel and the DAG/PKC/CPI-17 pathway were also involved.

CRISPR/Cas9-Based Dystrophin Restoration Reveals a Novel Role for Dystrophin in Bioenergetics and Stress Resistance of Muscle Progenitors.

Although the lack of dystrophin expression in muscle myofibers is the central cause of Duchenne muscular dystrophy (DMD), accumulating evidence suggests that DMD may also be a stem cell disease. Recent studies have revealed dystrophin expression in satellite cells and demonstrated that dystrophin deficiency is directly related to abnormalities in satellite cell polarity, asymmetric division, and epigenetic regulation, thus contributing to the manifestation of the DMD phenotype. Although metabolic and mitochondrial dysfunctions have also been associated with the DMD pathophysiology profile, interestingly, the role of dystrophin with respect to stem cells dysfunction has not been elucidated. In the past few years, editing of the gene that encodes dystrophin has emerged as a promising therapeutic approach for DMD, although the effects of dystrophin restoration in stem cells have not been addressed. Herein, we describe our use of a clustered regularly interspaced short palindromic repeats/Cas9-based system to correct the dystrophin mutation in dystrophic (mdx) muscle progenitor cells (MPCs) and show that the expression of dystrophin significantly improved cellular properties of the mdx MPCs in vitro. Our findings reveal that dystrophin-restored mdx MPCs demonstrated improvements in cell proliferation, differentiation, bioenergetics, and resistance to oxidative and endoplasmic reticulum stress. Furthermore, our in vivo studies demonstrated improved transplantation efficiency of the corrected MPCs in the muscles of mdx mice. Our results indicate that changes in cellular energetics and stress resistance via dystrophin restoration enhance muscle progenitor cell function, further validating that dystrophin plays a role in stem cell function and demonstrating the potential for new therapeutic approaches for DMD. Stem Cells 2019;37:1615-1628.

Inhibition of Cytomegalovirus Replication with Extended-Half-Life Synthetic Ozonides.

Artesunate (AS), a semisynthetic artemisinin approved for malaria therapy, inhibits human cytomegalovirus (HCMV) replication in vitro, but therapeutic success in humans has been variable. We hypothesized that the short in vivo half-life of AS may contribute to the different treatment outcomes. We tested novel synthetic ozonides with longer half-lives against HCMV in vitro and mouse cytomegalovirus (MCMV) in vivo Screening of the activities of four ozonides against a pp28-luciferase-expressing HCMV Towne recombinant identified OZ418 to have the best selectivity; its effective concentration inhibiting viral growth by 50% (EC50) was 9.8 ± 0.2 µM, and cytotoxicity in noninfected human fibroblasts (the concentration inhibiting cell growth by 50% [CC50]) was 128.1 ± 8.0 µM. In plaque reduction assays, OZ418 inhibited HCMV TB40 in a concentration-dependent manner as well as a ganciclovir (GCV)-resistant HCMV isolate. The combination of OZ418 and GCV was synergistic in HCMV inhibition in vitro Virus inhibition by OZ418 occurred at an early stage and was dependent on the cell density at the time of infection. OZ418 treatment reversed HCMV-mediated cell cycle progression and correlated with the reduction of HCMV-induced expression of pRb, E2F1, and cyclin-dependent kinases 1, 2, 4, and 6. In an MCMV model, once-daily oral administration of OZ418 had significantly improved efficacy against MCMV compared to that of twice-daily oral AS. A parallel pharmacokinetic study with a single oral dose of OZ418 or AS showed a prolonged plasma half-life and higher unbound concentrations of OZ418 than unbound concentrations of AS. In summary, ozonides are proposed to be potential therapeutics, alone or in combination with GCV, for HCMV infection in humans.

Form-Stable Solar Thermal Heat Packs Prepared by Impregnating Phase-Changing Materials within Carbon-Coated Copper Foams.

The heat packs that are based on solid-liquid transition of phase-changing materials (PCMs) have been pursued as a promising way to provide heating for human body comfort and thermotherapy owning to their large heat storage capacity and near-constant heat-release temperature. Current heat packs, however, suffer from leakage, slow charging, and poor heat-release performance due to the flow of liquid PCMs and their low thermal conductivity. Here, we report a strategy for preparing high-performance PCM-based solar thermal heat packs through impregnating organic PCMs within carbon-coated copper foams (CCFs). The porous structure and hydrophobic surface of CCF help to effectively confine the melted liquid PCM within the composite heat pack without leakage. The carbon coating layer efficiently converts the incident solar light into heat, which is rapidly transferred along the three-dimensional thermal conductive network of CCF and stored within the PCM. In the discharging process, the CCF network facilitates the extraction of the heat stored within the PCM. In contrast to neat PCM pack within which only a small portion of PCM that is in contact with human skin contributes to thermal comfort, all PCMs within the CCF-based composite heat pack concertedly release the stored heat. Such release significantly increases the extractable thermal energy and prolongs the usable healing duration for thermotherapy.

Indirubin suppresses ovarian cancer cell viabilities through the STAT3 signaling pathway.

BACKGROUND: Indirubin is the active component of Danggui Longhui Wan, a traditional Chinese medicine formulation. Due to its anti-inflammation and anti-tumor effects, indirubin has been widely used for the treatment of inflammation, cancer, and other chronic disease. Herein, we aimed to investigate the role and mechanism of indirubin in human ovarian cancer cell proliferation. MATERIALS AND METHODS: The cell viability was determined by Cell Counting Kit-8 and colony formation assays by treatment with different dosages of indirubin over 72 hours. Apoptosis was examined by flow cytometry with fluorescein isothiocyanate Annexin V Apoptosis Detection Kit. Western blot assay was finally applied to analyze the expression of cancer-related STAT3 pathway and its downstream proteins. RESULTS: Indirubin was found to significantly inhibit cell viability and induce apoptosis in 2 human ovarian cancer cell lines. Mechanistic studies revealed that indirubin treatment led to reduced levels of phosphorylated-STAT3, thus repressing the downstream pro-survival proteins and elevating pro-apoptosis ones. CONCLUSION: Our study provided the evidence for anti-survival activity of indirubin by inhibiting cell viability and inducing apoptosis in human ovarian cancer cells, which involved impaired STAT3 signaling pathway. Our findings further support indirubin as a potential drug candidate against human ovarian cancer.

A novel dual-luciferase assay for anti-HIV drug screening based on the CCR5/CXCR4 promoters.

Acquired immunodeficiency syndrome (AIDS) is a serious worldwide disease caused by infection with the human immunodeficiency virus (HIV). C-C chemokine receptor 5 (CCR5) and C-X-C chemokine receptor 4 (CXCR4) are important coreceptors mediating HIV-1 cell entry. Many new anti-HIV drugs are currently in preclinical and clinical trials; however, drug development has proceeded slowly partly because of the lack of a high-throughput system to screen these drugs. Here, we describe the development of a novel dual-luciferase assay using a CCR5/CXCR4 promoter-driven firefly and Renilla luciferase vector (pGL4.10-RLUC-CCR5/CXCR4). Drugs were screened for the ability to regulate CCR5 and CXCR4 promoter activities. The CCR5 and CXCR4 promoters were inserted separately into the recombinant vector and transfected into the acute T lymphocyte leukemia cell line H9. Treatment of stable transfected cells with four traditional Chinese medicine compounds resulted in the dose-dependent inhibition of the CXCR4 and CCR5 promoter activities. The dual-luciferase reporter assay provides a rapid and direct method to screen anti-AIDS/HIV drugs.

Polydatin Prevents Methylglyoxal-Induced Apoptosis through Reducing Oxidative Stress and Improving Mitochondrial Function in Human Umbilical Vein Endothelial Cells.

Methylglyoxal (MGO), an active metabolite of glucose, has been reported to induce vascular cell apoptosis in diabetic complication. Polydatin (PD), a small natural compound from Polygonum cuspidatum, has a number of biological functions, such as antioxidative, anti-inflammatory, and nephroprotective properties. However, the protective effects of PD on MGO-induced apoptosis in endothelial cells remain to be elucidated. In this study, human umbilical vein endothelial cells (HUVECs) were used to explore the effects of PD on MGO-induced cell apoptosis and the possible mechanism involved. HUVECs were pretreated with PD for 2 h, followed by stimulation with MGO. Then cell apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) impairment, mitochondrial morphology alterations, and Akt phosphorylation were assessed. The results demonstrated that PD significantly prevented MGO-induced HUVEC apoptosis. PD pretreatment also significantly inhibited MGO-induced ROS production, MMP impairment, mitochondrial morphology changes, and Akt dephosphorylation. These results and the experiments involving N-acetyl cysteine (antioxidant), Cyclosporin A (mitochondrial protector), and LY294002 (Akt inhibitor) suggest that PD prevents MGO-induced HUVEC apoptosis, at least in part, through inhibiting oxidative stress, maintaining mitochondrial function, and activating Akt pathway. All of these data indicate the potential application of PD for the treatment of diabetic vascular complication.

Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2 Signaling Pathway.

BACKGROUND: The flowers of Carthamus tinctorius L. are widely used in traditional Chinese medicine to treat cerebrovascular and cardiovascular diseases. Hydroxysafflor yellow A (HSYA), the main constituent of C. tinctorius L. flowers, is known for its multiple biological activities. The present study investigated the effects of HSYA on angiogenesis in vitro and in a mouse hindlimb ischemia model. METHODS: Using human umbilical vein endothelial cells (HUVEC) in vitro and a mouse hindlimb ischemia model in vivo, the angiogenic role of HSYA was evaluated. RESULTS: HSYA significantly increased the capillary-like tube formation and migration of HUVEC. HSYA not only induced a rise in the expression of angiopoietin 1 and Tie-2 but it also increased phosphorylation of Tie-2, Akt, and extracellular signal-regulated kinase 1/2. Furthermore, an anti-Tie-2 neutralizing antibody significantly inhibited HSYA-induced HUVEC tube formation and migration. In vivo, the recovery of perfusion of ischemic hindlimb tissue after femoral artery interruption was significantly increased in HSYA-treated mice compared to vehicle controls. Consistent with these results, the arteriole and capillary densities in ischemic gastrocnemius muscles were significantly increased in HSYA-treated mice. CONCLUSIONS: These results indicate the potential utility of HSYA for the treatment of ischemic diseases.

Scutellarin protects cardiomyocyte ischemia-reperfusion injury by reducing apoptosis and oxidative stress.

AIMS: Ischemic heart disease is a leading cause of death and disability worldwide. Despite recent advances, there is no effective therapy for preventing myocardial ischemia-reperfusion (I/R) injury. In this study, we aimed to examine the therapeutic effect of scutellarin, a flavone isolated from the traditional Chinese medicine Scutellaria barbata and Erigeron breviscapus, on cardiomyocyte I/R injury. MAIN METHODS: Neonatal rat cardiomyoblast cells H9C2 were used to study the role of scutellarin in cardiomyocyte injury. I/R injury was induced by 2h of hypoxia plus glucose and serum deprivation, followed by 6-hour recovery. Cardiomyocyte damage was evaluated by the release of pro-inflammatory cytokines and creatine kinase (CK), apoptosis, and cell proliferation. Oxidative responses were assessed by reactive oxygen species (ROS) production, MDA generation, SOD expression, and mitochondrial membrane potential detection. Activation of JAK2/STAT3 signaling and expression of pro- or anti-survival molecules were detected by Western blot. KEY FINDINGS: I/R injury increased the release of CK as well as pro-inflammatory cytokines TNFα, IL-1ß, IL-6, and IL-8 from cardiomyocytes. ROS, MDA, and apoptosis were enhanced in cardiomyocytes underwent I/R injury, while cell proliferation, mitochondrial membrane potential, SOD expression were reduced. Scutellarin treatment dose-dependently suppressed I/R injury-induced pro-inflammatory cytokine and CK release, oxidative response, loss of mitochondrial membrane potential, and enhanced cell proliferation and anti-oxidant SOD expression. Further analysis suggests scutellarin promotes JAK/STAT3 activation and expression of pro-survival proteins Bcl2, VEGF, MMP2, and MMP9. Pro-apoptotic molecules Bax and caspase-3 were suppressed by scutellarin. SIGNIFICANCE: We identified a previously unrecognized pathway by which scutellarin protects myocardial I/R injury. Scutellarin modulates I/R injury-induced oxidative stress and apoptosis probably by enhancing JAK2/STAT3 pro-survival signaling.

Bioinspired Bifunctional Membrane for Efficient Clean Water Generation.

Solving the problems of water pollution and water shortage is an urgent need for the sustainable development of modern society. Different approaches, including distillation, filtration, and photocatalytic degradation, have been developed for the purification of contaminated water and the generation of clean water. In this study, we explored a new approach that uses solar light for both water purification and clean water generation. A bifunctional membrane consisting of a top layer of TiO2 nanoparticles (NPs), a middle layer of Au NPs, and a bottom layer of anodized aluminum oxide (AAO) was designed and fabricated through multiple filtration processes. Such a design enables both TiO2 NP-based photocatalytic function and Au NP-based solar-driven plasmonic evaporation. With the integration of these two functions into a single membrane, both the purification of contaminated water through photocatalytic degradation and the generation of clean water through evaporation were demonstrated using simulated solar illumination. Such a demonstration should also help open up a new strategy for maximizing solar energy conversion and utilization.