Biomimetic Melanosomes Promote Orientation-Selective Delivery and Melanocyte Pigmentation in the H2O2-Induced Vitiligo Mouse Model.

Extremely limited drug retention and depigmentation represent the greatest barriers against vitiligo treatment advancement. Here, inspired by biological melanosomes, the primary melanin transporter, we developed biomimetic melanosomes to combat reactive oxygen species (ROS)-mediated melanocyte damage and depigmentation. Briefly, methylprednisolone (MPS) and melanin-mimicking polydopamine (PDA) were encapsulated inside lysine-proline-valine (KPV)-modified deformable liposomes (KPV-Lipos). Owing to their phospholipid bilayer flexibility and the specific affinity for melanocortin 1 receptor (MC1R), KPV-Lipos exhibited 1.43-fold greater skin deposition than traditional liposomes. The binding of KPV and its receptor also contributed to activating the cAMP-tyrosinase (TYR) signaling pathway, improving the endogenous melanin content. In addition, PDA mimicked melanosomes as it effectively increased the exogenous melanin content and scavenged ROS. Meanwhile, MPS inhibited inflammatory cytokine secretion, limiting the depigmented area. Ultimately, the biomimetic melanosomes affected the skin color of mice with H2O2-induced vitiligo. These melanosomes show potential as a universal platform for the self-supply of melanin by self-driven melanin synthesis with exogenous supplementation. Furthermore, this study offers ideas for the production of artificial packed melanosome substitutes for melanocyte-related diseases.

Simvastatin pretreatment protects cerebrum from neuronal injury by decreasing the expressions of phosphor-CaMK II and AQP4 in ischemic stroke rats.

Excitotoxicity and cytotoxic edema are the two major factors resulting in neuronal injury during brain ischemia and reperfusion. Ca2+/calmodulin-dependent protein kinase II (CaMK II), the downstream signal molecular of N-methyl-D-aspartate receptors (NMDARs), is a mediator in the excitotoxicity. Aquaporin 4 (AQP4), expressed mainly in the brain, is an important aquaporin to control the flux of water. In a previous study, we had reported that pretreatment of simvastatin protected the cerebrum from ischemia and reperfusion injury by decreasing neurological deficit score and infarct area (Zhu et al. PLoS One 7:e51552, 2012). The present study used a middle cerebral artery occlusion (MCAO) model to further explore the pleiotropic effect of simvastatin via CaMK II and AQP4. The results showed that simvastatin reduced degenerated cells and brain edema while decreasing the protein expressions of phosphor-CaMK II and AQP4, and increasing the ratios of Bcl-2/Bax, which was independent of cholesterol-lowering effect. Immunocomplexes formed between the subunit of NMDARs-NR3A and AQP4 were detected for the first time. It was concluded that simvastatin could protect the cerebrum from neuronal excitotoxicity and cytotoxic edema by downregulating the expressions of phosphor-CaMK II and AQP4, and that the interaction between NR3A and AQP4 might provide the base for AQP4 involving in the signaling pathways mediated by NMDARs.

Repeated electroacupuncture attenuating of apelin expression and function in the rostral ventrolateral medulla in stress-induced hypertensive rats.

Studies have revealed that apelin is a novel multifunctional peptide implicated both in blood pressure (BP) regulation and cardiac function control. Evidence shows that apelin and its receptor (APJ) in the rostral ventrolateral medulla (RVLM) may play an important role in central BP regulation; however, its role is controversial and very few reports have shown the relationship between acupuncture and apelin. Our study aims to both investigate the apelinergic system role in stress-induced hypertension (SIH) and determine whether acupuncture therapy effects on hypertension involve the apelinergic system in the RVLM. We established the stress-induced hypertensive rat (SIHR) model using electric foot-shock stressors with noise interventions. The expression of both apelin and the APJ receptor in the RVLM neurons was examined by immunohistochemical staining and Western blots. The results showed apelin expression increased remarkably in SIHR while APJ receptor expression showed no significant difference between control and SIHR groups. Microinjection of apelin-13 into the RVLM of control rats or SIHR produced pressor and tachycardic effects. Furthermore, effects induced by apelin-13 in SIHR were significantly greater than those of control rats. In addition, repetitive electroacupuncture (EA) stimulation at the Zusanli (ST-36) acupoint attenuated hypertension and apelin expression in the RVLM in SIHR; it also attenuated the pressor effect elicited by exogenous apelin-13 microinjection in SIHR. The results suggest that augmented apelin in the RVLM was part of the manifestations of SIH; the antihypertensive effects of EA might be associated with the attenuation of apelin expression and function in the RVLM, which might be a novel role for EA in SIH setting.

[Effects of Rb1 and Rg1 on the expression of Bcl-2, Bax in apoptosis of HK-2 cells induced by the serum of kidney ischemia/reperfusion].

AIM: To explore effects of Ginsenosides (Rb1, Rg1) on the expression of Bcl-2, Bax in the serum of kidney ischemia/reperfusion inducing apoptosis of HK-2 cells. METHODS: The serum of rabbits with renal ischemia/reperfusion (SIR) and the control serum of rabbits (SC) were acquired and cultured with HK-2 cells. Detected apoptosis with TUNEL assay. The experiment was designed as: control group,ischemia/ reperfusion group, Rb1 blocking group and Rg1 blocking group. To detect the expression of Bcl-2, Bax with immunocytochemistry after 24 hours' cultured. RESULTS: The expression of Bax in Rb1 blocking group and Rg1 blocking group were significantly decreased (P < 0.01), the ratios of Bcl-2/Bax were increased as compared with ischemia/reperfusion group. CONCLUSION: Rb1 and Rg1 have protective effects on apoptosis of HK-2 cells induced by serum of kidney ischemia/reperfusion.

[The investigation of HEV epidemiology, inferior clinical infection and viral-toxemia in blood donors in Quzhou area].

OBJECTIVE: To investigate the infection of HEV in Quzhou area of Zhejiang Province. METHODS: All sera from blood donors in the central blood bank of Quzhou from April 2006 to April 2007 were used. Anti-HEV IgG and anti-HEV IgM were measured by EIA. RT-PCR was also performed to the samples with positive anti-HEV IgM. Genotype and sequence homology were analyzed after sequencing. RESULTS: The positive ratio of anti-HEV IgG was 40.60%, in which the male infection ratio was higher than the female significantly (43.09% VS 36.09%; chi2=22.6; P < 0.01). The infection ratio was increased with age. The positive ratio of anti-HEV IgM was 0.43%. The positive ratio of anti-HEV IgG and the titers of antibody were higher in the inferior clinical infectors with positive anti-HEV IgM than the negative ones (P < 0.05). Two samples were positive in HEV PCR among 21 samples with positive anti-HEV IgM. The toxemia ratio was 0.4% of all the donors. And the genotype of the two samples with toxemia were both HEV-IV. CONCLUSION: The HEV infection was correlation with age and sex significantly and the infection occurred in the adults mainly in Quzhou area. HEV toxemia was not infrequency in the blood donors.