Targeted delivery of TGF-β mRNA to lung parenchyma using one-component ionizable amphiphilic Janus Dendrimers.

Current clinical strategies for the delivery of pulmonary therapeutics to the lung are primarily targeted to the upper portions of the airways. However, targeted delivery to the lower regions of the lung is necessary for the treatment of parenchymal lung injury and disease. Here, we have developed an mRNA therapeutic for the lower lung using one-component Ionizable Amphiphilic Janus Dendrimers (IAJDs) as a delivery vehicle.

[Effects of three Polyphenolic compounds on the intestinal flora of mice exposed simulated intermittent plateau hypoxia].

Objective: To investigate the protective effects of three Polyphenolic compounds on intestinal microbial communities in mice exposed intermittent plateau hypoxia.

Methods: In this study, 60 healthy male Balb/c mice were randomly divided into plain control group, plateau control group, primary anthocyanin intervention group, quercetin intervention group and resveratrol intervention group, 12 mice in each group. Primary anthocyanin, quercetin and resveratrol were administrated by gavage at the doses of 50, 100 and 20 mg/kg in pharmacological intervention group, respectively.

[Antifatigue effects of the composition of Moringa oleifera leaves and Polygonatum polysaccharide and its mechanisms].

To investigate the anti-fatigue effects of composition of Moringa oleifera leaves and Polygonatum polysaccharide, and to explore the mechanisms. Thirty male Kunming mice were randomly divided into control (C) and composition of Moringa oleifera leaves and Polygonatum polysaccharide group (MP). There were 15 mice in each group.

[Effects of nutritional preparation on HPO axis function and energy metabolism in uterus and ovary of rats exposed to intermittent cold].

To investigate the effects of a self-designed nutritional preparation on hypothalamic-pituitary-ovarian (HPO) axis function and energy metabolism in female SD rats exposed to intermittent cold. Female SD rats were divided into control group, cold exposure group and nutritional preparation group. The control group and cold exposure group were given distilled water by daily gavage, and the nutritional preparation group was given nutritional preparation intragastrically.

Surfactant protein-D modulation of pulmonary macrophage phenotype is controlled by -nitrosylation.

Surfactant protein-D (SP-D) is a regulator of pulmonary innate immunity whose oligomeric state can be altered through -nitrosylation to regulate its signaling function in macrophages. Here, we examined how nitrosylation of SP-D alters the phenotypic response of macrophages to stimuli both in vivo and in vitro. Bronchoalveolar lavage (BAL) from C57BL6/J and SP-D-overexpressing (SP-D OE) mice was incubated with RAW264.

[Effects of MAPKs inhibitors on GSH metabolic enzymes in rat hepatocytes].

Objective: To investigate the effects of mitogen-activated protein kinases (MAPKs) inhibitors on glutathione (GSH) metabolism, and to explore the pathway related to GSH metabolism.

Methods: BRL rat hepatocytes were treated by c-Jun NH2-terminal kinase (JNK),p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors:SP600125, SB203580 and PD98659, respectively, for 24 h. MTT method was used to measure hepatocytes viability.

Copper disrupts S-nitrosothiol signaling in activated BV2 microglia.

Microglia, the primary resident immune cells of the central nervous system (CNS), responds rapidly to pathogens and injury by secreting immune mediators including nitric oxide (NO). The reaction of NO with the anti-oxidant glutathione forms S-nitrosoglutathione (GSNO), the major pool of biologic NO in the body. GSNO is degraded by GSNO reductase (GSNOR).

Pharmacological targeting of VEGFR signaling with axitinib inhibits Tsc2-null lesion growth in the mouse model of lymphangioleiomyomatosis.

Pulmonary lymphangioleiomyomatosis (LAM), a rare progressive lung disease associated with mutations of the tuberous sclerosis complex 2 (Tsc2) tumor suppressor gene, manifests by neoplastic growth of LAM cells, induction of cystic lung destruction, and respiratory failure. LAM severity correlates with upregulation in serum of the prolymphangiogenic vascular endothelial growth factor D (VEGF-D) that distinguishes LAM from other cystic diseases. The goals of our study was to determine whether Tsc2 deficiency upregulates VEGF-D, and whether axitinib, the Food and Drug Administration-approved small-molecule inhibitor of VEGF receptor (VEGFR) signaling, will reduce Tsc2-null lung lesion growth in a mouse model of LAM.

The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice.

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component.

Anti-fibrotic effects of the Masson pine pollen aqueous extract on hepatic fibrosis rat model.

Aim: To observe the antifibrotic effects of Masson Pine Pollen aqueous extract.

Methods: Adult Sprague-Dawley rats were randomly divided into control (CG), hepatic fibrosis model (MG), MPPAE low dose (LG), MPPAE high dose (HG), and MPP original powder (MPPOP; OG) groups. Each group was treated with specific protocols and sacrificed 8 weeks later.

Pharyngeal wall floppiness: a novel technique to detect upper airway collapsibility in patients with OSAS.

Objective: To measure pharyngeal wall floppiness (PWF) under different pressures, a novel method and technique were introduced in the present study.

Study Design: A prospective clinical study.

Subjects And Methods: Forty-seven healthy subjects (32 male; mean age, 37.

Surfactant dysfunction and lung inflammation in the female mouse model of lymphangioleiomyomatosis.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare lung disease caused by mutations of the tumor suppressor genes, tuberous sclerosis complex (TSC) 1 or TSC2. LAM affects women almost exclusively, and it is characterized by neoplastic growth of atypical smooth muscle-like TSC2-null LAM cells in the pulmonary interstitium, cystic destruction of lung parenchyma, and progressive decline in lung function. In this study, we hypothesized that TSC2-null lesions promote a proinflammatory environment, which contributes to lung parenchyma destruction.

NOS2 is critical to the development of emphysema in Sftpd deficient mice but does not affect surfactant homeostasis.

Rationale: Surfactant protein D (SP-D) has important immuno-modulatory properties. The absence of SP-D results in an inducible NO synthase (iNOS, coded by NOS2 gene) related chronic inflammation, development of emphysema-like pathophysiology and alterations of surfactant homeostasis.

Objective: In order to test the hypothesis that SP-D deficiency related abnormalities in pulmonary structure and function are a consequence of iNOS induced inflammation, we generated SP-D and iNOS double knockout mice (DiNOS).

Disruption of the blood-brain barrier after generalized tonic-clonic seizures correlates with cerebrospinal fluid MMP-9 levels.

Background: Increasing evidence suggests seizures cause blood-brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation.

Tocopherol supplementation reduces NO production and pulmonary inflammatory response to bleomycin.

Bleomycin causes acute lung injury through production of reactive species and initiation of inflammation. Previous work has shown alteration to the production of reactive oxygen species results in attenuation of injury. Vitamin E, in particular, γ-tocopherol, isoform, has the potential to scavenge reactive oxygen and nitrogen species.

Copper modulates the phenotypic response of activated BV2 microglia through the release of nitric oxide.

Microglia are resident immune cells of the central nervous system. Their persistent activation in neurodegenerative diseases, traditionally attributed to neuronal dysfunction, may be due to a microglial failure to modulate the release of cytotoxic mediators such as nitric oxide (NO). The persistent activation of microglia with the subsequent release of NO vis-á-vis the accumulation of redox transition metals such as copper (Cu) in neurodegenerative diseases, prompted the hypothesis that copper would alter NO signaling by changing the redox environment of the cell and that, by altering the fate of NO, microglia would adopt a different phenotype.

Atypical PKCζ transduces electrophilic fatty acid signaling in pulmonary epithelial cells.

Nitric oxide and secondary oxides of nitrogen react with unsaturated fatty acids such as linoleic acid to yield oxidized and nitrated products. Fatty acid nitroalkene derivatives, (e.g.

[Improvement effect of vitamins B1, B2 and PP supplementation on substance metabolism of mice exposed to acute hypoxia].

Objective: To explore the improvement effect of vitamins B1, B2, PP supplementation to the metabolism changes of carbohydrates, lipids, protein and energy in mice exposed to acute hypoxia.

Methods: Fifty male Kunming mice were randomly divided into normal, acute hypoxia, acute hypoxia plus 2 times, 4 times and 8 times vitamins B1, B2, PP supplemented groups. All mice were fed corresponding diets for two weeks and then except the normal group were exposed to a simulated altitude of 6 000 meters for 8 hours.

Early alveolar epithelial dysfunction promotes lung inflammation in a mouse model of Hermansky-Pudlak syndrome.

Rationale: The pulmonary phenotype of Hermansky-Pudlak syndrome (HPS) in adults includes foamy alveolar type 2 cells, inflammation, and lung remodeling, but there is no information about ontogeny or early disease mediators.

Objectives: To establish the ontogeny of HPS lung disease in an animal model, examine disease mediators, and relate them to patients with HPS1.

Methods: Mice with mutations in both HPS1/pale ear and HPS2/AP3B1/pearl (EPPE mice) were studied longitudinally.

[The metabolic changes of mice serum after loaded swimming].

Objective: To investigate the metabolic changes of mice serum after loaded swimming and to provide a basis for the study of anti-fatigue functional food.

Methods: The male Kunming mice were randomly divided into four group, fed an AIN-93 diet for 14 days, and forced to swim for 30, 60 or 120 min, respectively, with a load on their tails. The mice were executed after swimming immediately and the changes of serum metabolic profiles were analyzed using metabolomic approach.

Substance P inhibits natural killer cell cytotoxicity through the neurokinin-1 receptor.

SP is a potent neuroimmunomodulator that functions through ligating members of the neurokinin receptor family, one of which, NK1R, is widely expressed in immune cells. As in humans, circulating SP levels are increased in pathologic states associated with impairment of NK cell functions, such as depression and HIV infection, we hypothesized that SP has a direct, inhibitory effect upon NK cells. We have studied a clonal human NK cell line (YTS) as well as ex vivo human NK cells and have determined that truncated and full-length NK1R isoforms are expressed in and SP bound by ex vivo NK cells and the YTS NK cell line.

Metabolomic study on vitamins B₁, B₂, and PP supplementation to improve serum metabolic profiles in mice under acute hypoxia based on ¹H NMR analysis.

Objective: To explore metabolic changes after acute hypoxia and modulating effect of vitamins B₁, B₂, and PP supplementation in mice exposed to acute hypoxia.

Methods: Fifty male Kunming mice were randomly divided into 5 groups: normal, acute hypoxia, acute hypoxia with 2, 4 and 8 time-vitamins B₁, B₂, and PP supplementation. All mice were fed with corresponding diets for two weeks and then were exposed to a simulated altitude of 6,000 meters for 8 h, except for the normal group.

[Phospholamban antisense RNA transfer attenuates post-infarction remodeling and preserves cardiac functions].

Objective: To investigate whether the gene transfer of phospholamban antisense RNA could inhibit remodeling and preserve cardiac function after myocardial infarction.

Methods: Wistar rats received a ligation of left coronary with a direct intramyocardial injection of phospholamban antisense RNA eukaryote vector PcDNA4-asPLB. The cardiac function, hemodynamics and ventricular geometry of three groups (shame, saline injection and PcDNA4-asPLB injection) were studied by echocardiography and left ventricle hemodynamic recording.

[Hyperfine structure study of binary sodium phosphates by Raman spectroscopy].

Quantum chemistry ab initio calculation was applied to study the hyperfine structure of binary sodium phosphates. A series of phosphate model clusters were designed to simulate the microstructure of phosphates with different components. Closed-shell Hatree-Fock method (RHF) and the basis sets of 6-31G (d, p) were employed to optimize structures and calculate Raman frequencies of these phosphate model clusters.

[Effects of acute hypoxia on plasma metabolome in mice].

Aim: To explore the metabolic effects of acute hypoxia on mice plasma.

Methods: Fourteen mice were randomly divided into two groups: control and hypoxia group. The mice of hypoxia group were exposed to a simulated altitude of 6000 meters for 8 hours.