Introducing High Density of Very Active Sites and Stepwise Postmodification for Tailoring the Porosity of Highly Demanding Cr3+-Based Metal-Organic Frameworks.

Chromium(III)-based metal-organic frameworks (Cr-MOFs) are highly robust and porous and have been very attractive in a wide range of investigations. However, the harsh direct synthetic conditions not only impede the synthesis of new Cr-MOFs but also restrict the introduction of functional groups into them. Postsynthetic modification has somewhat alleviated such difficulties; nevertheless, it still suffered from procedures that are tedious and conditions that are not mild, which often result in low concentration of the functional groups introduced. To overcome these shortcomings, here, in this paper, we supplied a new route and prepared a benzyl alcohol functionalized Cr-SXU-2 from the judiciously designed benzyl alcohol functionalized Fe-SXU-2 through solvent-assisted metal metathesis strategy. The functionalized Cr-SXU-2 shows well-preserved crystallinity, porosity, and high chemical stability. The benzyl alcohol group can be converted into a very active benzyl bromide group in an almost quantitative yield and thus for the first time produce the benzyl bromide functionalized MOF, Cr-SXU-2-Br, in which the -Br group can be exchanged by a nucleophilic group. As a proof of concept, -N3 was introduced and transformed into other active sites via "click reaction" to further tailor the interior of Cr-SXU-2. All these functionalized Cr-MOFs showed improved adsorption performance in contrast to the nonfunctionalized one. This step-by-step postmodification process not only diversifies the functionalization of robust MOFs but also opens a new route to employ many different functional groups in the demanding highly stable Cr-MOF platforms.

Approaches to developing fast release pellets via wet extrusion-spheronization.

Microcrystalline cellulose (MCC) is widely regarded as the excellent choice to manufacture pellets via wet extrusion-spheronisation (ES) process due to its excellent water uptake capability, water holding capacity, desirable rheological properties, cohesiveness and plasticity etc. Nevertheless, in spite of all these advantages, limitations associated with the application of MCC also have been reported. The most prevailing limitation is prolonged or incomplete drug release profile due to the lack of disintegration as pellet contracts significantly during the drying process, especially when in combination with poorly soluble drug at a high level. This characteristic limits the application of MCC in immediate release formulations. Over the years, many approaches have been tried to overcome this disadvantage, such as modifying MCC, incorporation of superdisintegrant, increasing the porosity of pellet, partial or complete substitution for MCC, enhancing the solubility of poorly soluble drug (e.g. solid dispersion, self-emulsifying drug-delivery system), etc. In this review, we will provide an updated and integrated discussion of current approaches to prepare fast release pellets via wet ES.

Gastrointestinal stability of dihydromyricetin, myricetin, and myricitrin: an in vitro investigation.

The gastrointestinal (GI) stability of three flavonoids, dihydromyricetin (DMY), myricetin (MYR), and myricitrin (MYT), was examined in simulated physiological fluids. Several factors that may influence the degradation rate of theses flavonoids were evaluated, including pH and the presence of pepsin and pancreatin enzymes. We found that GI stability followed the order of MYT > DMY > MYR. These flavonoids were stable in simulated gastric fluids and buffer solutions (pH 1.2), but encountered a pseudo-first-order kinetic degradation in simulated intestinal fluids and buffer solutions (pH 6.8). We conclude that it is the pH, rather than the presence of pepsin or pancreatin, which most strongly influences the stability of these three flavonoids. Further study of the stability of the compounds using a pH range (1.0-8.0) indicated potential instability in the duodenum, small intestine, and colon. Therefore, we conclude that the low bioavailability of these flavonoids may be due to their poor stability in the GI tract.

[Analysis and exploration on adverse reactions of four kinds of andrographolide injections].

Concerned literature on four kinds of andrographolide injections in recent 15 years were searched in CNKI, Wanfang and VIP databases. The adverse drug reaction(ADR) cases of Chuanhuning, Yanhuning, Xiyanping and Lianbizhi injections were classified and analyzed statistically, including a total of 194 articles and 3 479 cases. The ADR clinical characteristics and occurrence regularity of these four andrographolide injections were analyzed and compared from the gender, age, primary disease, emergence time of ADR, clinical manifestation, allergy history, dosage, prognosis and combined medication of the patients. It is useful to provide valuable references for rational use of these andrographolide injections in clinical practice.

Anti-HSV-1 effect of dihydromyricetin from Ampelopsis grossedentata via the TLR9-dependent anti-inflammatory pathway.

OBJECTIVES: Herpes simplex virus 1 (HSV-1) is one of the most prevalent viruses in humans worldwide. Owing to limited therapeutic options mainly with acyclovir (ACV) and analogues and the emergence of ACV-resistant strains, new drugs with different modes of action and low toxicity are required. The aim of this study was to determine the anti-HSV-1 effect and mechanism of action of the flavonoid compound dihydromyricetin (DHM) from Ampelopsis grossedentata. METHODS: The HSV-1 inhibitory effect of DHM was evaluated by measuring plaque formation and generation of progeny virus as well as expression of HSV-1-related genes in Vero cells. The molecular mechanism of the antiviral activity of DHM against HSV-1 was explored by real-time quantitative PCR and ELISA. RESULTS: DHM presented a significant inhibitory effect on HSV-1 plaque formation and generation of progeny virus, with an EC50 (50% effective concentration) of 12.56 µM in Vero cells. Furthermore, expression of HSV-1 immediate-early genes (ICP4 and ICP22), early genes (ICP8 and UL42) and late genes (gB, VP1/2) was decreased by DHM at concentrations of 16 µM and 32 µM. DHM specifically suppressed mRNA levels of Toll-like receptor 9 (TLR9), leading to inhibition of the inflammatory transcriptional factor NFκB and a decrease in TNFα. CONCLUSION: These findings indicate that the effective inhibitory activity of DHM was achieved by suppressing TNFα production in a TLR9-dependent manner. Although further studies are needed to better characterise the activity of DHM in vivo, the results suggest this extract as a promising new anti-HSV-1 agent.

Uptake and Transport Mechanism of Dihydromyricetin Across Human Intestinal Caco-2 Cells.

A variety of beneficial pharmacological activities have been reported for dihydromyricetin (DMY), however, its oral bioavailability is poor and the intestinal absorption profiles of DMY remains unknown. The aim of this study was to investigate the uptake and transport mechanism of DMY in human intestinal Caco-2 cells. DMY was detected using a liquid chromatography-tandem mass spectrometry method. Several factors including time, concentration, pH, temperature and efflux transporters were systematically evaluated. DMY was poorly absorbed by a passive diffusion mechanism. The uptake and transport of DMY were time and concentration dependent. Interestingly, decreasing the pH from 8.0 to 6.0 markedly enhanced the DMY uptake, but didn't significantly affect its bidirectional transport. Efflux transporters, multidrug resistance protein 2 and breast cancer resistance protein also influenced the DMY uptake and transport processes. This work details the uptake and transport characteristics of DMY and provides basis for future study. PRACTICAL APPLICATION: This study elucidated the uptake and transport characteristics of dihydromyricetin (DMY). DMY was poorly absorbed by a passive diffusion mechanism. The uptake and transport of DMY were time and concentration dependent. Interestingly, pH affected DMY uptake but not its bidirectional transport. MRP2 and BCRP were involved in the uptake and transport of DMY, which hindered the absorption of DMY in the intestinal. Thus, the present study may provide useful information for designing DMY delivery systems and avoiding DMY-drug interactions.

[Extract of acanthopanacis senticosus improves sperm motility of asthenospermia patients in vitro].

OBJECTIVE: To study the effect of different concentrations of the extract of acanthopanacis senticosus on human sperm motility in vitro and to investigate its possible mechanism. METHODS: By computer-assisted sperm analysis (CASA) system, we observed the effect of different concentrations of the extract of acanthopanacis senticosus on human sperm motility in vitro. The sperm obtained by masturbation and prepared by swim-up technique from 35 men with asthenospermia was incubated in different concentrations of the extract of acanthopanacis senticosus, and all the specimens were measured at 30, 60, 120 and 180 min respectively. RESULTS: Different concentrations of the extract of acanthopanacis senticosus obviously improved the sperm motility of asthenospermia patients. The extract at the concentrations of 5 and 10 g/L increased the rate of motility (MOT), the percentage of progressive mobile sperm, the curvilinear velocity (VCL), the straight line velocity (VSL) and the average path velocity (VAP). Compared with the control group, the difference was significant (P < 0.05). CONCLUSION: The extract of acanthopanacis senticosus can improve the sperm motility of asthenospermia patients in vitro and its optimal concentration is 10 g/L. The study may provide a new drug therapy for asthenospermia.

Shear Stress-sensitive Carriers for Localized Drug Delivery.

Stenosis of the critical blood vessels, which occurs in a variety of cardiovascular and cerebrovascular diseases, is one of leading causes of death in the world. Vascular stenosis will significantly alter the hemodynamic features in the vessel. Hemodynamic shear stress, one of the most important physical parameters of blood flow, will be dramatically elevated at the stenotic site. When platelets flow through the constricted site, they will sense these abnormally high shear stresses, and then respond by activating, sticking to the vascular wall, and aggregating at these sites. The shear-dependent platelet activation inspired a novel targeting platform-shear stress activated drug targeting delivery. The shear-activated drug delivery systems preferentially release their content under elevated shear stress, providing a novel approach to cure various diseases, in particular, cardiovascular diseases. In this review, we, on one hand, introduced the features of hemodynamic shear stress under both physiological and pathological conditions. On the other hand, we summarized the carriers displaying sensitivity to shear stress, such as liposomes, aggregations, gels, emulsions, in addition to the factors affecting the mechanical properties of them. Lastly, the clinical applications and prospects of this novel drug targeting strategy were discussed. It is hoped that, with a better understanding of shear stress-sensitive carriers and their targeted principle, a novel targeted drug delivery strategy will be one day applied in the clinics of the future.

[A citation analysis of Chinese Journal Of Plastic Surgery].

OBJECTIVE: The paper was to evaluate the quality and characteristics of the Chinese Journal of Plastic Surgery(CJPS). METHODS: With the database of Chinese Citation Index, the citation analysis was used to analyze the distribution of the cited original articles published in the CJPS from 2001 to 2005. RESULTS: 1045 papers were published during the period, and there were 530 (50.72%) cited by other researchers. The total frequency of citation was 1598, and each original article was averagely cited 3.02 times by other researchers. The published papers were cited by 289 journals and self-citing rate was 7.57%. The distribution of the most frequently cited authors covered 25 provinces, with Beijing, Shanghai, Shanxi and Guangdong Province in the lead in research work relevant to plastic medicine. CONCLUSIONS: The Chinese Journal of Plastic Surgery has published high quality articles in the past five years. It is one of the most important information resource for the Plastic Surgery researchers and of the most important medical journals.