Mesoporous silica nanoparticle-encapsulated Bifidobacterium attenuates brain Aß burden and improves olfactory dysfunction of APP/PS1 mice by nasal delivery.

BACKGROUND: Dysbiosis or imbalance of gut microbiota in Alzheimer's disease (AD) affects the production of short-chain fatty acids (SCFAs), whereas exogenous SCFAs supplementation exacerbates brain Aß burden in APP/PS1 mice. Bifidobacterium is the main producer of SCFAs in the gut flora, but oral administration of Bifidobacterium is ineffective due to strong acids and bile salts in the gastrointestinal tract. Therefore, regulating the levels of SCFAs in the gut is of great significance for AD treatment. METHODS: We investigated the feasibility of intranasal delivery of MSNs-Bifidobacterium (MSNs-Bi) to the gut and their effect on behavior and brain pathology in APP/PS1 mice. RESULTS: Mesoporous silica nanospheres (MSNs) were efficiently immobilized on the surface of Bifidobacterium. After intranasal administration, fluorescence imaging of MSNs-Bi in the abdominal cavity and gastrointestinal tract revealed that intranasally delivered MSNs-Bi could be transported through the brain to the peripheral intestine. Intranasal administration of MSNs-Bi not only inhibited intestinal inflammation and reduced brain Aß burden but also improved olfactory sensitivity in APP/PS1 mice. CONCLUSIONS: These findings suggested that restoring the balance of the gut microbiome contributes to ameliorating cognitive impairment in AD, and that intranasal administration of MSNs-Bi may be an effective therapeutic strategy for the prevention of AD and intestinal disease.

Curcumin loaded sub-30 nm targeting therapeutic lipid nanoparticles for synergistically blocking nasopharyngeal cancer growth and metastasis.

Systemic chemotherapy is still the primary treatment for advanced-stage nasopharyngeal carcinoma (NPC), but only limited therapeutic success has been achieved in the past decade because of drug resistance and systemic toxicity. Curcumin (Cur) is an effective alternative to chemotherapeutics because it showed remarkable therapeutic potential in the treatment of NPC. However, lack of tissue specificity and poor penetration in solid tumors are the major obstacles to effective therapy. Therefore, in this work, a self-assembled sub-30 nm therapeutic lipid nanoparticle loaded with Cur, named as Cur@α-NTP-LN, was constructed, specifically targeting scavenger receptor class B member 1 (SR-B1) and enhancing its therapeutic effects on NPC in vivo. Our results showed that Cur@α-NTP-LNs were effective and superior to free Cur on NPC cell-specific targeting, suppressing cell proliferation and inducing cell apoptosis. In vivo and ex vivo optical imaging revealed that Cur@α-NTP-LNs exerted high targeting efficiency, specifically accumulating in NPC xenograft tumors and delivering Cur into the tumor center after systemic administration. Furthermore, Cur@α-NTP-LNs exhibited a remarkable inhibitory effect on the growth of NPC subcutaneous tumors, with over 71 and 47% inhibition compared to Cur- and α-NTP-LNs-treated groups, respectively. In addition, Cur@α-NTP-LNs almost blocked NPC metastasis in a lung metastasis model of NPC and significantly improved the survival rate. Thus, the sub-30 nm Cur@α-NTP-LNs enhanced the solubility of Cur and demonstrated the ability of targeted Cur delivery into the center of the solid NPC tumor, performing synergistic inhibitory effects on the growth of NPC tumor and its metastasis with high efficiency.

Clinical pathways based on integrative medicine in chinese hospitals improve treatment outcomes for patients with acute myocardial infarction: a multicentre, nonrandomized historically controlled trial.

Objective. To determine the impact of an integrative medicine clinical pathways (CPs) on the length of in-hospital stay and on outcomes for patients with acute myocardial infarction (AMI). Methods. A multicenter nonrandomized controlled trial enrolling 197 consecutive patients with AMI at eight urban TCM hospitals was conducted between 1 January 2010 and 31 October 2010. These patients were enrolled in the interventional group after the CPs had been implemented. The control group included 405 patients with AMI from eight hospitals; these patients were treated between 1 January 2008 and 31 December 2009, before the CPs were implemented. Outcome measures were the length of hospital stay costs of medical care, and major cardiovascular events (MACEs) during hospitalization. Results. Compared with the control group, the patients in intervention group had a shorter length of hospital stay (9.2 ± 4.2 days versus 12.7 ± 8.6 days, P < 0.05), and reduced healthcare costs in hospital (46365.7 ± 18266.9 versus 52866.0 ± 35404.4, P < 0.05). There were statistically significant differences in MACE between the two groups during the hospitalization period (2.5% versus 6.9%, P = 0.03). Conclusion. These data suggest that the development and implementation of the clinical pathways based in Integrative Medicine could further improve quality of care and outcome for patients with AMI.

[Effects of the Chinese patent medicine, Honghua Injection, on platelet glycoprotein IIb/III a receptors in patients with acute coronary syndrome: a randomized controlled trial].

BACKGROUND: Glycoprotein (GP) IIb/IIIa is an important index for assessing the function of platelets. To investigate the effects of Honghua Injection, a Chinese patent medicine made from extracts of Carthamus tinctorius L, on GP IIb/IIIa is a key study in evaluating the inhibition properties of Honghua Injection on platelet aggregation. OBJECTIVE: To observe the effects of Honghua Injection on platelet GPIIb/IIIa receptors and explore the mechanisms of Honghua Injection in inhibiting platelet aggregation in patients with acute coronary syndrome. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 64 patients from Yueyang Hospital of Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine were randomly divided into Honghua Injection group (n=32, routine Western medicine plus Honghua Injection) and control group (n=32, routine Western medicine) according to the random number table. The patients were treated for 14 d. MAIN OUTCOME MEASURES: The expressions of GPIIb/IIIa (CD41), P-selection (CD62p), and lysosome-associated membrane GP (CD63) were measured by flow cytometry before and after treatment. Meanwhile the therapeutic effects of Huonghua Injection on angina and short-term prognosis were observed. RESULTS: The observational period was 14 d and four patients in the control group were omitted due to early discharge. The expression of CD41 in both the Honghua Injection group and the control group was inhibited after treatment (P<0.05, P<0.01). The inhibition of the Honghua Injection group was stronger than that of the control group (P<0.05). There was no case of death, myocardial infarction and cerebral apoplexy during 14 d of treatment. The improvement of angina symptoms and electrocardiographic manifestation in the Honghua Injection group was greater than that of the control group (P<0.05). CONCLUSION: Honghua Injection can inhibit the expression of GP IIb/IIIa receptors by preventing aggregation of platelets and may be considered as an effective traditional Chinese medicine for acute coronary syndrome.

Exploration of the relationship between phlegm-dampness constitution and polymorphism of low density lipoprotein receptor genes Pvu II and Ava II.

OBJECTIVE: To explore the polymorphism of low density lipoprotein receptor (LDL-R) genes Pvu II and Ava II in a population with phlegm-dampness constitution (PDC). METHODS: Polymorphism of LDL-R genes at Pvu II and Ava II of 48 persons with gentle constitution (GC) and 61 with PDC were analyzed with PCR-RELP technique, and their serum contents of lipids and glucose were determined and compared as well. RESULTS: The A+ allelic and P-allelic frequency were higher and the P+ allelic frequency was lower in subjects with PDC than those in subjects with GC, which were 0.3083 vs 0.1771, 0.9098 vs 0.7708 and 0.0902 vs 0.2292, respectively, all showing significant difference between the two groups (P<0.05). Comparison of the two groups in serum levels of triglyceride (TG), fasting blood glucose, 2 h postprandial blood glucose, and 2 h postprandial insulin showed that all the parameters were higher in subjects with PDC than in subjects with GC respectively, showing significant difference (P<0.05). CONCLUSION: PDC is related with the P- and A+ allelic frequency of higher LDL-R genes at Pvu II and Ava II, therefore, the polymorphism of LDL-R genes could be taken as one of the genetic markers for PDC, and humans with PDC are more liable to suffer from blood lipids and glucose disorder than those with GC.