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To observe the clinical effect of chicken-claw needling at Xiaguan (ST 7) combined with intradermal needling on negative emotion in primary trigeminal neuralgia (PTN) of phlegm obstruction and blood stasis.Sixty cases of patients with PTN of phlegm obstruction and blood stasis were randomly divided into an observation group and a control group, 30 cases in each group. The observation group was treated with chicken-claw needling at Xiaguan (ST 7) combined with intradermal needling (acupoints Sibai [ST 2], Yuyao [EX-HN 4], Hegu [LI 4], Taichong [LR 3] and auricular points Xin [COAfter treatment, the VAS, SAS, TCM syndrome scores and the contents of serum SP in the two groups were lower than those before treatment (Chicken-claw needling at Xiaguan (ST 7) combined with intradermal needling can relieve pain symptoms and negative emotions in patients with primary trigeminal neuralgia of phlegm obstruction and blood stasis, which may be related to the regulation of serum neurotransmitter levels.

Brain drug delivery remains a major difficulty for several challenges including the blood–brain barrier, lesion spot targeting, and stability during circulation. Blood cells including erythrocytes, platelets, and various subpopulations of leukocytes have distinct features such as long-circulation, natural targeting, and chemotaxis. The development of biomimetic drug delivery systems based on blood cells for brain drug delivery is growing fast by using living cells, membrane coating nanotechnology, or cell membrane-derived nanovesicles. Blood cell-based vehicles are superior delivery systems for their engineering feasibility and versatile delivery ability of chemicals, proteins, and all kinds of nanoparticles. Here, we focus on advances of blood cell-based biomimetic carriers for from blood to brain drug delivery and discuss their translational challenges in the future.

Therapeutic peptides (TPs) are biological macromolecules which can act as neurotransmitters, hormones, ion channel ligands and growth factors. Undoubtedly, TPs are crucial in modern medicine. But low bio-stability and some special adverse reactions reduce their places to the application. : With the development of nanotechnology, nanoparticles (NPs) in pharmaceutical science gained much attention. They can encapsulate the TPs into their membrane or shell. Therefore, they can protect the TPs against degradation and then increase the bioavailability, which was thought to be the biggest advantage of them. Additionally, targeting was also studied to improve the effect of TPs. However, there were some drawbacks of nano TPs like low loading efficiency and difficulty to manufacture. : Nowadays, lots of studies focused on improving effect of TPs by preparing nanoparticles. In this review, we presented a brief analysis of peptide-combined nanoparticles. Their advantages and disadvantages were listed in terms of mechanism. And several examples of applications were summarized.

Wen-qun Li,1–3,* Jun-yong Wu,1–3,* Da-xiong Xiang,1–3 Shi-lin Luo,1–3 Xiong-bin Hu,1–3 Tian-tian Tang,1–3 Tao-li Sun,4 Xin-yi Liu1–3 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha 410011, People’s Republic of China; 2Institution of Clinical Pharmacy, Central South University, Changsha 410011, People’s Republic of China; 3Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drugs, Changsha 410011, People’s Republic of China; 4Key Laboratory Breeding Base of Hu’nan Oriented Fundamental and Applied Research of Innovative Pharmaceutics, College of Pharmacy, Changsha Medical University, Changsha 410219, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin-yi LiuDepartment of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaTel +86-731-8529-2093Email liuxinyi128@csu.edu.cnBackground: The protective role of puerarin (PUE) against myocardial infarction is closely related to its regulation on mitochondria. However, free PUE can hardly reach the mitochondria of ischemic cardiomyocytes due to the lack of mitochondrial targeting of PUE. Here PUE was loaded into mitochondria-targeted micelles (PUE@TPP/PEG-PE) for precisely delivering PUE into mitochondria with the aim of enhancing the anti-apoptosis effect.Methods: The mitochondriotropic polymer TPP-PEG-PE was synthesized for the preparation of PUE@TPP/PEG-PE micelles modified with triphenylphosphonium (TPP) cation. The physicochemical properties and anti-apoptosis effect of PUE@TPP/PEG-PE micelles were investigated. The coumarin 6 (C6)-labeled TPP/PEG-PE (C6@TPP/PEG-PE) micelles were used to observe the enhanced cellular uptake, mitochondrial targeting and lysosomes escape. Moreover, in vivo and ex vivo biodistribution of lipophilic near-infrared dye 1,1ʹ-dioctadecyl-3,3,3′,3ʹ-tetramethylindotricarbocyanine iodide (DiR)-labeled PUE@TPP/PEG-PE (DiR@TPP/PEG-PE) micelles were detected through fluorescence imaging.Results: The successful synthesis of TPP-PEG-PE conjugate was confirmed. PUE@TPP/PEG-PE micelles had a particle size of 17.1 nm, a zeta potential of −6.2 mV, and a sustained-release behavior. The in vitro results showed that the intracellular uptake of C6@TPP/PEG-PE micelles was significantly enhanced in H9c2 cells. C6@TPP/PEG-PE micelles could deliver C6 to mitochondria and reduce the capture of lysosomes. In addition, compared with the PUE@PEG-PE micelles and free PUE, the PUE@TPP/PEG-PE micelles exerted an enhanced protective effect against isoprenaline-induced H9c2 cell apoptosis, as evident by the decreased percentage of apoptotic cells, Caspase-3 activity, ROS level, Bax expression, and increased Bcl-2 expression. The in vivo detecting results of the targeting effect using DiR probe also indicated that TPP/PEG-PE micelles could accumulate and retain in the ischemic myocardium.Conclusion: The results of this study demonstrate the promising potential of applying PUE@TPP/PEG-PE micelles in mitochondria-targeted drug delivery to achieve maximum therapeutic effects of PUE.Keywords: mitochondrial targeting, anti-apoptosis, ischemic myocardium, TPP

Background 3,5,4'-trimethoxy-trans-stilbene (BTM) is a methylated derivative of resveratrol. To improve the pharmaceutical properties of BTM, BTM loaded PEG-PE micelles (BTM@PEG-PE) were fabricated and its anti-cancer efficacy against colon cancer was evaluated. Methods BTM@PEG-PE micelles were prepared by the solvent evaporation method and were characterized by nuclear magnetic resonance (NMR), size, zeta potential, polymer disperse index (PDI) and transmission electron microscopy (TEM). Cellular uptake, cell viability assay, caspase-3 activity assay and flow cytometry were performed to evaluate the cell internalization and anti-cancer efficacy of BTM@PEG-PE micelles in vitro. Pharmacokinetic profiles of BTM and BTM@PEG-PE micelles were compared and in vivo anti-cancer therapeutic efficacy and safety of BTM@PEG-PE micelles on CT26 xenograft mice were evaluated. Results BTM was successfully embedded in the core of PEG-PE micelles, with a drug loading capacity of 5.62±0.80%. PEG-PE micelles facilitated BTM entering to the CT26 cells and BTM@PEG-PE micelles exerted enhanced anti-cancer efficacy against CT26 cells. BTM@PEG-PE micelles showed prolonged half-life and increased bioavailability. More importantly, BTM@PEG-PE micelles treatment suppressed tumor growth in tumor-bearing mice and prolonged survival with minimal damage to normal tissues. Conclusion Altogether, the BTM@PEG-PE micelles might be a promising strategy to enhance the pharmacokinetic and pharmacodynamic potentials of BTM for colon cancer therapy.

Purpose: The aim of this research was to develop a phospholipid complex based nanoemulsion system for oral insulin delivery. Methods: Insulin-phospholipid complex (IPC) was firstly prepared by an anhydrous co-solvent lyophilization method, and then encapsulated into the oil phase of nanoemulsion to obtain the IPC-based nanoemulsion (IPC-NE). Both water-in-oil (W/O) IPC-NE and oil-in-water (O/W) IPC-NE were formulated and evaluated for comparison. Results: The obtained W/O IPC-NE and O/W IPC-NE were both spherical in shape with a mean particle size of 18.6±0.79 nm and 27.3±1.25 nm, respectively. While both IPC-NEs exhibited enhanced Caco-2 cell monolayers permeability than IPC and insulin solution, W/O IPC-NE showed relatively greater protective effects against enzymatic degradation than O/W IPC-NE. Moreover, oral administration of W/O IPC-NE exhibited significant hypoglycemic effects, with 12.4-fold and 1.5-fold higher oral bioavailability compared with insulin solution and O/W IPC-NE, respectively. Conclusion: IPC-NEs, especially the W/O IPC-NE showed promising efficiency in vitro and in vivo, thus could be a potential strategy for oral insulin delivery.

Background 8-methoxypsoralen (8-MOP) is one of the most commonly utilized drugs in psoralen-ultraviolet A therapy for treatment of vitiligo. However, poor skin retention and systemic side effects limit the clinical application of 8-MOP. Methods Microemulsions (MEs) and chitosan derivative-coated 8-MOP MEs were developed and compared for dermal delivery of 8-MOP. Ex vivo skin retention/permeation study was performed to select the ME formulation with the highest retention:permeation ratio. Four different chitosan-coated MEs were prepared and compared with the ME formulation for their ability to distribute 8-MOP in the skin. Results Among various ME formulations developed, a formulation containing 2.9% ethyl oleate, 17.2% Cromophor EL35, 8.6% ethanol and 71.3% water showed the highest ex vivo skin retention:permeation ratio (1.98). Of four chitosan-coated MEs prepared, carboxymethyl chitosan-coated MEs (CC-MEs) and hydroxypropyl chitosan-coated MEs (HC-MEs) showed higher ex vivo skin retention:permeation ratio (1.46 and 1.84). and were selected for in vivo pharmacokinetic study. AUCskin (0-12 h) for 8-MOP MEs (4578.56 h·ng·mL-1) was higher than HC-MEs (3422.47 h·ng·mL-1), CC-MEs (2808.51 h·ng·mL-1) and tincture (1500.16 h·ng·mL-1). Also, AUCplasma (0-12 h) for MEs (39.35±13.90 h·ng·mL-1) was significantly lower than HC-MEs (66.32 h·ng·mL-1), CC-MEs (59.70 h·ng·mL-1) and tincture (73.02 h·ng·mL-1). Conclusion These combined results suggested that the MEs developed could be a promising and safe alternative for targeted skin delivery of 8-MOP.

Dense extracellular matrix (ECM) in the tumor stroma has been a challenge for drug penetration and cytotoxic T lymphocyte (CTL) infiltration. Neutrophil elastase (NE), in surface-bound form, can destruct ECM rapidly, may be used for remodeling tumor ECM, and overcoming tumor stromal barrier. Focusing on elastosis in triple-negative breast tumor, biomimetic liposomes with chimeric cell membrane proteins (LMP) are developed and for the first time, it is demonstrated that LMP with surface-bound elastase (NE-LMP) can target and degrade ECM effectively in tumor stroma, with minimal toxicity to normal tissues. The pretreatment of NE-LMP increases the accumulation of chemotherapeutics at the tumor site and enhances antitumor effects. Also, NE-LMP facilitates CTL infiltration in tumors and exhibits enhanced chemo-immunotherapy in combination of PD-1 immune checkpoint blockade treatment in orthotopic 4T1 tumor-bearing mice, with significantly prolonged survival. Moreover, the remodeling of the tumor ECM by NE-LMP shows inhibiting effects on metastasis in the lung. Findings from this study suggest that NE-LMP holds promise for enhancing deep penetration of drug and infiltration of CTL in desmoplastic tumor by effective degrading ECM in the tumor stroma.

Exosomes (Exos) are promising vehicles for brain drug delivery due to nanosize and the ability to breach the blood-brain barrier (BBB). But the low yield of natural exosomes limits its application for nanomedicine. The generation of bioinspired nanovesicles (BNVs) that mimicking Exos is attractive, but there is a lack of comparative evaluation of Exos and BNVs. Here, we perform the first head-to-head comparison study of Exos and BNVs for brain tumor drug delivery. We show that BNVs derived from brain-derived endothelial cells are competent alternative nanocarrier to natural exosomes. The drug-loading capacity of Exos and BNVs are similar, but the yield of BNVs is substantially higher (500-fold) than Exos. Doxorubicin (DOX)-loaded BNVs (BNV/DOX) and DOX-loaded Exos (Exo/DOX) showed similar pharmacokinetic profiles and prolonged circulation od DOX. Despite inconsistent mechanisms, BNV/DOX can across the BBB, and exhibit suppression effects similar to Exo/DOX on the progress of glioblastoma (GBM) in zebrafish and in vivo subcutaneous and orthotopic xenografts mice models, with minimal systemic toxicity. Findings from this head-to-head comparison study indicate that autologous BNVs is a effective alternative of Exos for brain tumor nanomedicine.

For therapy of skin cancer, transdermal administration has been a potential way to enhance chemotherapy. However, the drug delivery efficacy remained unsatisfactory because of the physiological barriers from the skin to the tumor, which hindered the effect of 3,5,4'-trimethoxy-trans-stilbene (BTM), a drug that has toxicity to cancer. Herein, we prepared an oil-in-water (O/W) microemulsion to load BTM (BTM-ME) for transdermal therapy of melanoma. BTM-ME was characterized by size, zeta potential, and polymer disperse index (PDI). B16F10 melanoma cell line was used for cell experiments and animal models. And cell uptake, viability assay, and flow cytometry were to test the cell internalization and the ability of BTM-ME to induce cancer cell apoptosis. Skin penetration testing was to detect its penetration efficiency to the skin. And tumor-bearing mice were used to prove the improvement of anti-cancer efficacy of BTM-ME with the combination of Taxol. BTM was successfully loaded in O/W microemulsion, with a drug loading capacity of 24.82 mg/mL. BTM-ME can penetrate the skin and increase the retention of BTM in the epidermis. And the combination of Taxol and BTM-ME effectively suppressed tumor growth and has lower toxicity to normal organs. BTM-ME provides adjuvant therapy to cutaneous melanoma and the combination of Taxol and BTM-ME has the clinical potential for skin cancer therapy. Graphical abstract.

The aim of this study was to develop a microemulsion-based hydrogel (MBH) formulation of 3,5,4′-trimethoxy-trans-stilbene (BTM) as topical delivery system for the treatment of osteoarthritis (OA). The pseudo-ternary phase diagrams were constructed to optimize the microemulsion (ME) formulation. The ME formulation containing 18.8% Cremopher EL35 (surfactant), 9.4% Transcutol HP (co-surfactant), 3.1% LABRAFIL M 1944 CS (oil), and 68.7% water was selected. The obtained BTM-loaded ME (BTM-ME) had a spherical morphology (17.5 ± 1.4 nm), with polydispersity index (PDI) value of 0.068 ± 0.016 and zeta potential of − 11.8 ± 0.5 mV, and was converted into BTM-loaded MBH (BTM-MBH) using Carbopol 940. Ex vivo skin permeation study showed that both ME and MBH formulations significantly enhanced the amount of BTM permeated. The cumulative amount of BTM permeated after 12 h (Q12) for ME, and MBH formulations were 3.25- and 1.96-fold higher than that for emulsion gel (EG). Pharmacokinetic study showed that the AUC of BTM suspension (oral) was three times higher than that of BTM-MBH (topical). Topical delivery of BTM-MBH demonstrated remarkable anti-OA effect in a rabbit model of OA induced by papain, with decreased levels of pro-inflammatory cytokines. The developed MBH formulation might be a promising strategy for topical delivery of BTM for treatment of OA.

C20H30O4, orthorhombic, P21212 (no. 18), a = 12.6727(4) Å, b = 19.8422(7) Å, c = 7.5471(3) Å, V = 1897.75(12) Å3, Z = 2, Rgt (F) = 0.0448, wR ref(F 2) = 0.1311, T = 243(2) K.

Berberine hydrochloride (BBH) has a variety of pharmacological activities such as antitumor, antimicrobial, anti-inflammation, and reduce irritable bowel syndrome. However, poor stability and low oral bioavailability limited its usage. Herein, an oil-in-water nanoemulsion system of BBH was developed to improve its stability and oral bioavailability. The pseudoternary phase diagrams were constructed for the determination of composition of various nanoemulsions. The nanoemulsions of BBH composed of Labrafil M 1944 CS (oil phase), RH-40 (surfactant), glycerin (co-surfactant), and water (aqueous phase). The O/W nanoemulsion of BBH showed a relative bioavailability of 440.40% compared with unencapsulated BBH and was stable in our 6-month stability study. Further, there was a significant increase in intestinal permeability of BBH as assessed by Caco-2 cell monolayers and a significant reduction in efflux of BBH by the multidrug efflux pump P-glycoprotein. This study confirmed that the nanoemulsion formulation could be used as an alternative oral formulation of BBH to improve its stability, oral bioavailability and permeability.

Background 3,5,4′-trimethoxy-trans-stilbene (BTM) is a methylated derivative of resveratrol. To improve the pharmaceutical properties of BTM, BTM loaded PEG-PE micelles (BTM@PEG-PE) were fabricated and its anti-cancer efficacy against colon cancer was evaluated. Methods BTM@PEG-PE micelles were prepared by the solvent evaporation method and were characterized by nuclear magnetic resonance (NMR), size, zeta potential, polymer disperse index (PDI) and transmission electron microscopy (TEM). Cellular uptake, cell viability assay, caspase-3 activity assay and flow cytometry were performed to evaluate the cell internalization and anti-cancer efficacy of BTM@PEG-PE micelles in vitro. Pharmacokinetic profiles of BTM and BTM@PEG-PE micelles were compared and in vivo anti-cancer therapeutic efficacy and safety of BTM@PEG-PE micelles on CT26 xenograft mice were evaluated. Results BTM was successfully embedded in the core of PEG-PE micelles, with a drug loading capacity of 5.62±0.80%. PEG-PE micelles facilitated BTM entering to the CT26 cells and BTM@PEG-PE micelles exerted enhanced anti-cancer efficacy against CT26 cells. BTM@PEG-PE micelles showed prolonged half-life and increased bioavailability. More importantly, BTM@PEG-PE micelles treatment suppressed tumor growth in tumor-bearing mice and prolonged survival with minimal damage to normal tissues. Conclusion Altogether, the BTM@PEG-PE micelles might be a promising strategy to enhance the pharmacokinetic and pharmacodynamic potentials of BTM for colon cancer therapy.

Background 8-methoxypsoralen (8-MOP) is one of the most commonly utilized drugs in psoralen-ultraviolet A therapy for treatment of vitiligo. However, poor skin retention and systemic side effects limit the clinical application of 8-MOP. Methods Microemulsions (MEs) and chitosan derivative-coated 8-MOP MEs were developed and compared for dermal delivery of 8-MOP. Ex vivo skin retention/permeation study was performed to select the ME formulation with the highest retention:permeation ratio. Four different chitosan-coated MEs were prepared and compared with the ME formulation for their ability to distribute 8-MOP in the skin. Results Among various ME formulations developed, a formulation containing 2.9% ethyl oleate, 17.2% Cromophor EL35, 8.6% ethanol and 71.3% water showed the highest ex vivo skin retention:permeation ratio (1.98). Of four chitosan-coated MEs prepared, carboxymethyl chitosan-coated MEs (CC-MEs) and hydroxypropyl chitosan-coated MEs (HC-MEs) showed higher ex vivo skin retention:permeation ratio (1.46 and 1.84). and were selected for in vivo pharmacokinetic study. AUCskin (0–12 h) for 8-MOP MEs (4578.56 h·ng·mL−1) was higher than HC-MEs (3422.47 h·ng·mL−1), CC-MEs (2808.51 h·ng·mL−1) and tincture (1500.16 h·ng·mL−1). Also, AUCplasma (0–12 h) for MEs (39.35±13.90 h·ng·mL−1) was significantly lower than HC-MEs (66.32 h·ng·mL−1), CC-MEs (59.70 h·ng·mL−1) and tincture (73.02 h·ng·mL−1). Conclusion These combined results suggested that the MEs developed could be a promising and safe alternative for targeted skin delivery of 8-MOP.

SUMMARY Systemic dissemination of microbes is critical for progression of many infectious diseases and is associated with most mortality due to bacterial infection. The physical mechanisms mediating a key dissemination step, bacterial association with vascular endothelia in blood vessels, remain unknown. Here, we show that endothelial interactions of the Lyme disease spirochete Borrelia burgdorferi under physiological shear stress mechanistically resemble selectin-dependent leukocyte rolling. Specifically, these interactions are mediated by transfer of mechanical load along a series of adhesion complexes and are stabilized by tethers and catch bond properties of the bacterial adhesin BBK32. Furthermore, we found that the forces imposed on adhesive bonds under flow may be small enough to permit active migration driven by bacterial flagellar motors. These findings provide insight into the biomechanics of bacterial-vascular interactions and demonstrate that disseminating bacteria and circulating host immune cells share widely conserved mechanisms for interacting with endothelia under physiological shear stress., In Brief Bacteria overcome forces generated by blood flow in order to adhere to vascular surfaces during spread of blood-borne infections. The biomechanics of this process are not understood. Ebady et al. show that bacteria exploit force generated by blood flow to strengthen their interactions with endothelia using mechanisms that are remarkably similar to the mechanisms supporting leukocyte rolling on vascular surfaces.

Puerarin (PUE) and tetramethylpyrazine (TMP) are central nervous system (CNS) drugs used in cerebrovascular diseases. Poor brain–blood barrier (BBB) permeability limited their clinical application. Borneol and α-asarone have been proposed as an oral brain-targeting enhancer. In this study, we aimed to first evaluate the ‘orifice-opening’ effect of borneol and α-asarone, both aromatic resuscitation drugs, on improvement of brain delivery of PUE and TMP and second to investigate whether the enhancing effects were associated with adenosine receptors (ARs)-mediated trans-BBB pathway. In vitro BBB model was established and borneol and α-asarone significantly increased the cumulative amount of permeated PUE and TMP and the enhancing effects could be counteracted by AR inhibitors. Borneol and α-asarone could decrease expression of ZO-1, an important BBB junction protein, but inversely increase the expression of A1AR and A2AAR. In vivo pharmacokinetic study also confirmed that oral co-administration of borneol or α-asarone significantly increased AUCbrain for PUE and TMP. These results suggested that borneol and α-asarone are both effective adjuvant agents for delivery of PUE and TMP to the brain.

This paper investigates the flux distributions of the electron photo-detached from H− ion localized in a gradient electric field. In contrast with the photodetachment in the uniform electric field [Phys. Rev. A 40 (1989) 4983], where only two electron trajectories interfere at each given point on a detector, for the photodetachment in a gradient electric field, the electrons waves can travel along multiple paths from the negative ion to a given point on the detector plane, which makes the electron flux distributions on the detector plane become much complex. Using the semi-classical theory, we put forward a formula for calculating the electron flux. Our calculation results suggest that the electron flux distributions on a given detector plane is not only related to the propagation time of the detached electron, but also related to the detached electron's energy. With the increase of the detached electron's energy, the oscillating region in the electron flux distributions becomes enlarged and the oscillating structure in the flux distributions becomes much more complicated. This study will guide future experiment research on the photodetachment microscopy of the negative ions in the presence of non-uniform external fields.

Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption.

Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

We show that the photodetachment of H− in an electric field near a metal surface can be controlled by using a single or double laser pulse. The method of theoretical analysis used is semi-classical closed orbit theory. The results show that if the period of a certain closed orbit is longer than the pulse width of the single-pulse laser, the contribution of that closed orbit to the photodetachment cross-section will be greatly reduced. As for the double-pulse laser, the pulse width, phase difference and the time delay between the two pulses all play an important role in the photodetachment cross-section. With the decrease of the time delay, the oscillating amplitude of the cross-section increases while the oscillating frequency decreases. Therefore, laser pulses can be used to control the photodetachment process of negative ions or atoms in an external field near metal surfaces.

The photodetachment of hydrogen negative ion in the magnetic field near a metal surface is studied using a semiclassical theory of photodetachment microscopy. During photodetachment of H– in the pr...

FLZ is a synthetic novel squamosamide derivative and has previously been proved to be a potential drug for Parkinson's disease and Alzheimer's disease. FLZ has strong antioxidant activity, which implies that FLZ could eliminate excessive intracellular reactive oxygen species (ROS) in tumor cells and induce a pathway related to low cellular ROS levels, thereby inhibiting tumor cells proliferation. However, few reports have focused on the antitumor effects of FLZ. In this study, we investigated the antitumor efficacy of FLZ in HepG2 cells and the mechanism of cell growth inhibition. FLZ effectively inhibited HepG2 cell proliferation in a dose- and time-dependent manner; meanwhile, it was minimally toxic to normal cells. FLZ induced a significant decrease in oxidative stress through elimination of excessive intracellular ROS and strengthening of the glutathione antioxidant system. In addition, FLZ can effectively attenuate redundant [Ca(2+)](i), thereby avoiding uncontrolled amplification by Ca(2+)/ROS positive feedback. Furthermore, Western blot showed that FLZ inhibited phosphorylation of Akt and retinoblastoma protein (Rb), down-regulated the expressions of cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2), and enhanced the expression of CDK inhibitor p27(kip1), while did not affect CDK4 expression. These results suggest that FLZ has potent anti-proliferative activity against malignant human hepatoma cells via modulation of the expression or activation of cell-cycle regulatory proteins, which are associated with decreased Ca(2+)/ROS levels, and indicate that FLZ is a potential liver cancer drug worthy of further research and development.

The photodetachment of a homo-nuclear diatomic molecular negative ion with arbitrary molecular axis orientation has been studied using the two-centre model. An analytic formula is presented for the photodetached electron flux distribution at a given observation plane. This formula is universal, applicable to all homo-nuclear diatomic molecular negative ions. Taking as an example, we calculate the electron flux distribution and photodetachment cross section for different molecular axis orientations. The results show that the molecular axis orientation has a great influence on the photodetachment of the diatomic molecular negative ion. The oscillation of the electron flux distribution is largest for the molecular axis perpendicular to the laser light polarized along the z direction and is smallest for the parallel molecular axis orientation. Our studies suggest that we can control the photodetachment process of the molecular negative ion by changing the molecular axis orientation. Our research will be helpf...

Using the closed orbit theory, we give a clear physical picture description of the photodetachment of H − in the magnetic field near a metal surface. The photodetachment cross-section of this system is also derived and calculated. It is found that the effect of the metal surface can be considered as a varying electric field. The detached electron's motion and the cross-section are similar to the case of the photodetachment of H − in parallel electric and magnetic fields. For a given ion-surface distance, the cross-section depends sensitively on the magnetic field strength. As the magnetic field strength is weak, the cross-section is the same as the photodetachment of H − near a metal surface. With the increase of the magnetic field strength, the number of the closed orbits increases and the photodetachment cross-section becomes much more complicated. This study provides a new understanding on the photodetachment process of negative ions in the presence of external fields and surfaces.

The aim of this study is to explore the tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats. Healthy male SD rats were randomly divided into two groups (30 each). Both were given PEGylated puerarin at a dose of 488 mg x kg(-1). After 5 min of medication, one group was normal rats, another group with acute myocardial ischemia was established by peritoneal injection of 50 mg x kg(-1) isoprenaline. After administration, the animals were executed at 30, 60, 90, 120, 150 and 180 min, then heart, liver, spleen, lung, kidney were extracted. The content of puerarin in organ tissue was determined by HPLC. The results showed that the AUC of tissue distribution of PEGylated puerarin in normal rats was liverkidneyheart ≈ spleenlungbrain. While the AUC of tissue distribution of PEGylated puerarin in acute myocardial ischemia model rats was liver ≈ heartkidneylung ≈ spleenbrain. AUC(heart) of PEGylated puerarin in acute myocardial ischemia model rats was 1.7 times than that of the normal rats, and there was significant difference (P0.05). Thus, PEGylated puerarin had a good heart-targeting property in early myocardial infarction area, drugs could accumulate in the ischemic myocardium. It provided important information for further study and clinic use of PEGylated puerarin.

The soil drought stress experiment in different durations (no watering within 3d, 6d, 9d, 11d individually) was conducted to study the drought-resistant capacity of one-year-old seedlings for the native tree species (Machilus yunnanensis) in Yunnan Province and the introduced tree species (Cinnamomum camphora). The leaf water potential, chlorophyll content, proline content and plasma membrane permeability for two species seedlings were measured in different soil drought conditions. The results showed that, on the 9th day of drought stress, the leaf water potential of two species decreased obviously, whereas the free proline content and plasma membrane permeability increased sharply. On the 11th day, the leaf water potential of C. camphora seedlings was lower than that of M. yunnanensis seedlings; the plasma membrane permeability in C. camphora seedling leaves increased much more than that in M. yunnanensis seedling leaves, which showed that the injury to the former by soil drought stress was more severe than that to the latter. The free proline content in M. yunnanensis seedling leaves continued to increase on the 11th day, but that in the C. camphora seedling leaves started to drop obviously, indicating that the reduction of osmotic regulation substance in C. camphora seedling leaves after the 11th day was unable to maintain the osmotic balance between the plasma system and its surroundings and the water loss occurred inevitably. Comprehensively, M. yunnanensis seedlings enhanced the drought-resistance in the course of soil drought stress by maintaining higher leaf water potential and by increasing osmotic regulation substance to promote cell plasma concentration and maintain membrane structure integrity so as to reduce water loss. The subordination function index evaluated with fuzzy mathematic theory also showed that the drought-resistant capacity of M. yunnanensis seedlings was stronger than that of C. camphora seedlings.

Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.

The ionization dynamics of a Rydberg hydrogen atom in a generalized van der Waals potential is studied using a semiclassical analysis of photoionization microscopy. Interference patterns of the 2-D radial probability density of the electrons escaping from a photoionization process have been calculated to simulate the patterns recorded on a position-sensitive detector. The added contributions from different ionization trajectories from the atom to the detector generate the interference pattern. The interference pattern is sensitive to one of the parameters governing the electron motion in the generalized van der Waals potential. The photoionization microscopy pattern can therefore be controlled by changes in the external potential.

This study is to screen 23 blank O/W type microemulsion (ME) samples, that is 15 samples from our laboratory, and 8 samples from literature; compare the conductivity-water content curve (CWCC) method and visual method in determining the critical water content during O/W type MEs' formation, to analyze the deficiency and the feasibility of visual method and to exploxe scientific meanings of CWCC method in judging the critical water content of O/W type MEs during formation. The results show that there is a significant difference between the theoretical feasible CWCC method and visual method in determining the critical water content (P0.001), and the results judged by conductivity is higher than that by eye-based water content. Therefore, this article firmly confirmed the shortcomings of visual method and suggested that the eye-base "critical water content" may falls into continuous ME stage during O/W MEs' formation. Further more, the CWCC method has theoretical feasibility and scientific meanings in determining the critical water content of O/W type MEs during formation.

To study the changes of serum interleukin-2 (IL-2), interleukin-8 (IL-8) and immunoglobulin (IgG, IgA, IgM) in patients with esophageal cancer, and to probe the relationship between the levels of IL-2, IL-8, IgG, IgA and IgM and the progress of cancer.The serum levels of IL-2 and IL-8 were detected by enzyme-linked immunosorbent assay for 72 case of primary esophageal cancer, 68 advanced esophageal cancer and 120 healthy controls, and the level of immunoglobulin (IgG, IgA, IgM) in patients with esophageal cancer was dynamically observed.The IL-2 level in patients with early esophageal cancer [(1.69 +/- 0.53) ng/ml] or late esophageal cancer [(1.11 +/- 0.60) ng/ml] was lower than the control group [(2.78 +/- 0.51) ng/ml] (P0.01), the late esophageal cancer group was lower than early esophageal cancer group (P0.05). The level of IL-8 in patients with early esophageal cancer [(85.48 +/- 6.14) ng/L] or late esophageal cancer [(121.41 +/- 6.22) ng/L] was much higher than the control group [(54.48 +/- 12.20) ng/L] (P0.01), the late esophageal cancer group was much higher than early esophageal cancer group (P0.01); There was correlation between the levels of IL-2 and IL-8 and the worsen-extent of the tumour in patients with early esophageal cancer or late esophageal cancer. But the level of IgG [(12.23 +/- 2.50) g/L], IgM [(1.60 +/- 0.80) g/L] in the patients with esophageal cancer compared with the level of IgG [(11.65 +/- 3.70) g/L], IgM [(1.46 +/- 0.71) g/L] in the health control group have no significant difference (P0.05), the level of IgA [(3.50 +/- 1.10) g/L] in patients with esophageal cancer Compared with the control group [(1.88 +/- 1.08) g/L] has significant difference (P0.01), and along with the worsen-extent of the tumor in patients the level of IgA has the increased tendency.The IL-8 might accelerate the pathogenesis of esophageal cancer, and the IL-2 might restrain. The positive correlation between the level of IgA and the patients with esophageal cancer is observed in this study; the immune maladjustment of IL-2, IL-8 and IgA might be correlative to esophageal cancer, and the IL-2, IL-8 and IgA levels might be an available index for the severity of esophageal cancer, Which may be of some help for clinic practitioners to judge the progress, curative effect and prognosis of the cancer.

Tian-Tian Tang,1,2,3 Xiong-Bin Hu,1,2,3 De-Hua Liao,1,2,3 Xin-Yi Liu,1,2,3 Da-Xiong Xiang1,2,31Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China; 2Institute of Clinical Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China; 3Key Laboratory for New Technology of Chinese Medicine Preparations of Hunan Province, Changsha, People's Republic of ChinaAbstract: The purpose of the present work was to determine the mechanisms by which microemulsions (MEs) enhance the oral bioavailability of puerarin. The in situ perfusion method was used in rats to study the absorption mechanisms of an oil-in-water (O/W) microemulsion (O/W-ME) and a water-in-oil (W/O) microemulsion (W/O-ME). The possibility of lymphatic transport of the MEs was investigated using a chylomicron flow blocking approach. The results for the absorption mechanisms in the stomach and intestines indicated that the absorption characteristics of the O/W-ME and W/O-ME depend on the segment. The W/O-ME had higher internal membrane permeability than the O/W-ME. The results of the lymphatic transport analyses showed that both the O/W-ME and W/O-ME underwent lymphatic transport and that this pathway was a major contributor to the oral bioavailability of MEs. Furthermore, the type of ME can significantly affect the absorption of puerarin through the lymphatic system due to the oil content and the form of the microemulsion after oral administration. In conclusion, these data indicate that microemulsions are an effective and promising delivery system to enhance the oral bioavailability of poorly water-soluble drugs.Keywords: microemulsion, lymphatic transport, oral bioavailability, chylomicron

Using the first order classical perturbation theory and the time-dependent closed orbit theory, we study the photodetachment of H - near a metal surface plus a weak oscillating electric field for the first time. The results show that the oscillating electric field can reduce the strength of the photodetachment cross section. The influence of the oscillating electric field is not only related to its strength, but also related to the distance from the ion to the metal surface. For a given ion–surface distance, with the increase of the strength of the oscillating electric field, the oscillating amplitude in the photodetachment cross section was decreased greatly. Besides, for a given oscillating electric field, with the increase of the ion–surface distance, its influence becomes much more obvious. As the ion–surface distance is very large, even a very weak oscillating electric field can weaken the photodetachment cross section of H - near a metal surface greatly. This study provides a new understanding on th...