Therapeutic effect of transplanted umbilical cord mesenchymal stem cells in a cynomolgus monkey model of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease affecting 2.5 million young people worldwide because of its immune-mediated pathological mechanisms. Recent studies have shown that stem cell transplantation is a new potential therapy for MS. There has been renewed interest in cell therapy to improve quality of life for MS patients. In this study, the experimental autoimmune encephalomyelitis (EAE) model, which is the most commonly model to mimic MS, was successfully established in cynomolgus monkeys. To evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (UCMSCs) on MS, we intravenously transplanted UCMSCs into cynomolgus monkeys with EAE. Our results showed that UCMSC transplantation significantly ameliorated the clinical symptoms of MS. Magnetic resonance imaging and clinical signs indicated that demyelination was obviously decreased after UCMSCs therapy. Moreover, the present study showed that the mechanisms, involved in the effects of UCMSCs on MS, included their immunomodulatory functions to regulate cytokine secretion and affect functional differentiation of the T cell lineage.

The Dual Role of HIV-1 gp120 V3 Loop-Induced Autophagy in the Survival and Apoptosis of the Primary Rat Hippocampal Neurons.

HIV-1 gp120, an important subunit of the envelope spikes that decorate the surface of virions, is known to play a vital role in neuronal injury during HIV-1-associated neurocognitive disorder (HAND), although the pathological mechanism is not fully understood. Our previous studies have suggested that the V3 loop of HIV-1 gp120 (HIV-1 gp120 V3 loop) can induce neuronal apoptosis in the hippocampus, resulting in impairment in spatial learning and memory in Sprague-Dawley (SD) rats. In this study, we demonstrated that autophagy was significantly increased in rat primary hippocampal neurons in response to treatment of HIV-1 gp120 V3 loop. Importantly, HIV-1 gp120 V3 loop-induced autophagy played a dual role in the cell survival and death. An increase in autophagy for a short period inhibited apoptosis of neurons, while persistent autophagy over an extended period of time played a detrimental role by augmenting the apoptotic cascade in rat primary hippocampal neurons. In addition, we found that the HIV-1 gp120 V3 loop induced autophagy via AMPK/mTOR-dependent and calpain/mTOR-independent pathways, and the ERK/mTOR pathway plays a partial role. These findings provide evidence that HIV-1-induced autophagy plays a dual role in the survival and apoptosis of the primary rat hippocampal neurons and persistent autophagy may contribute to the pathogenesis of HAND, and autophagy modulation may represent a potential therapeutic strategy for reducing neuronal damage in HAND.

Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis.

Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9) and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop) protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K(+)) current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K(+) channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K(+) channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K(+) current.

Curcumin ameliorates hippocampal neuron damage induced by human immunodeficiency virus-1.

Our previous studies have shown that infection with the gp120 V3 loop can cause human immunodeficiency virus-1 associated neurocognitive disorders. Curcumin has been shown to improve these effects to some degree, but the precise mechanisms remain unknown. The present study analyzed the neuroprotective effect and mechanism of curcumin in relation to hippocampal neurons. Results showed that 1 nmol/L gp120 V3 loop suppressed the growth of synapses. After administration of 1 µmol/L curcumin, synaptic growth improved. Curcumin is neuroprotective against gp120 V3 loop-induced neuronal damage by inhibiting the activation of L-type calcium currents, relieving intracellular Ca(2+) overload, promoting Bcl-2 expression, and inhibiting Bax activation. The effect of curcumin was identical to nimodipine, suggesting that curcumin has the same neuroprotective effects against gp120 V3 loop-induced neuronal damage.

[Protective effect and mechanism of curcumin on ActD/TNF-α-induced synergistically apoptosis in PC12 cells].

AIM: To investigate the protective effect and mechanism of curcumin against ActD/TNF-α-induced synergistically apoptosis in PC12 cells. METHODS: MTT assay was used to evaluate the optimal concentration of drugs; Hoechst 33258 fluorescent staining to observe apoptosis of PC12 cells, JC-1 was used to detect the mitochondrial membrane potential (MMP), real-time PCR was used to detect the expression of two apoptotic genes: Bcl-1 and Bax. RESULTS: ActD/TNF-α can synergistically reduce viability of PC12 cells(P<0.05), increase the number of cells with pyknosis and karyorrhexis, increase apoptotic rate of cells (P<0.05), decrease MMP in cells, and downregulate expression of Bcl-2(P<0.05). After treating with curcumin(5 µmol/L), survival of PC12 cells was increased(P<0.05), the number of cells with pyknosis and karyorrhexis was reduced, MMP and expression of Bcl-2 were increased(P<0.05). CONCLUSION: Curcumin can resist the ActD/TNF-α-induced synergistically apoptosis in PC12 cells, the mechanisms of which may be related to an increase in MMP and Bcl-2 expression.

[Determination of N-nitrosodiethanolamine in cosmetics by isotope dilution-liquid chromatography-tandem mass spectrometry].

A comprehensive analytical method based on isotope dilution-liquid chromatography-tandem mass spectrometry has been developed for the determination of N-nitrosodiethanolamine in cosmetics. Water-soluble cosmetic samples were extracted with water. The extract was centrifuged, then the upper solution was cleaned up by an Oasis HLB solid phase extraction cartridge. Oil-soluble cosmetic samples were extracted by liquid-liquid partition with dichloromethane and water. Qualitative and quantitative analyses were carried out for the analyte under the multiple reaction monitoring (MRM) mode after the chromatographic separation on a Waters Atlantis T3 column (150 mm x 2.1 mm, 3 microm ). The quantitation was performed with deuterated N-nitrosodiethanolamine as internal standard. The limit of quantitation (LOQ) for N-nitrosodiethanolamine was 50 microg/kg. The mean recoveries were 89.1%-98.2% at the spiked levels of 50-250 microg/kg, with the intra-day precision less than 9% and the inter-day precision less than 11%. The method is suitable for the determination of NDELA in cosmetics.

Moisturizing and anti-sebum secretion effects of cosmetic application on human facial skin.

For human skin, high water content and low sebum secretion are considered to be main features of fair skin. To explore the proper personal care regimen for facial skin, we investigated the change of skin physiologic parameters after cosmetic application by measuring the skin water content, transepidermal water loss, and skin sebum secretion on facial skin before and after the cosmetic application using the Corneometer, Tewameter, and Sebumeter, respectively. The results indicated that the cosmetics application kept a higher water content and a lower transepidermal water loss, and at the same time, a lower sebum secretion 4 h and 8 h after the cosmetic application, compared with those before it. The situation was maintained in the succeeding three-week continuous use of the cosmetics. It could be concluded that the cosmetic application on human facial skin might provide some moisturizing effect and at the same time an anti-sebum effect, which favors the maintenance of good skin physiological function after applying skin care products. Our results might provide a scientific personal care regimen for human facial skin to prompt the balance for the hydrolipid film on skin.

[Determination of perfluorooctanoic acid and its salts in the coating layer of nonstick pan by gas chromatography/mass spectrometry coupled with accelerated solvent extractor].

A sensitive, accurate and reproducible analytical method was developed and validated to quantify perfluorooctanoic acid (PFOA) and its salts in the coating layer of nonstick pan. Scraped samples of 0. 5 gram were directly extracted with acetonitrile using an accelerated solvent extractor at 175 degrees C, 10. 3 MPa for 20 min. After rotary evaporation concentration, the PFOA was derivatized with acetyl chloride and methanol at 65 degrees C for 60 min in an air-tight container. An HP-1 MS capillary column (30 m x 0. 25 mm, 0. 33 degrees m) was used for the separation of the analyte. The procedure for the analysis of PFOA was based on gas chromatography interfaced to negative chemical ion mass spectrometry, operated in selected ion monitoring mode. Selected ions of m/z 312, 350, 378, 408, 428 were chosen for quantitation. The assay was linear over the range of 0 - 1 000 microg/L, and the detection limit of PFOA was 5 microg/kg. The precision and recovery were assessed on four different concentrations (5, 20, 100, 500 micro/kg). The recoveries were in the range of 90. 9% - 96. 2% and the relative standard deviations were 1. 37% -6. 37%. The procedure was applied to monitoring PFOA in the coating layer of nonstick pan from supermarket and no positive result was found.