Gene mutation of Candida albicans is one of the main causes for azole drug resistance. Different types of variation play different roles in promoting the process of drug resistance. ERG series of gene mutations primarily affect the ergosterol synthesis pathway. When the regulatory factors TAC1 for CDR1 gene and Mrr1 for MDR1 gene generate mutations, the expression level of drug efflux pump protein in Candida albicans may be changed. In addition, gene copy number variation is also gaining attention. Therefore, the research of mutation resistance-associated genes has a positive meaning to explore the mechanism of drug resistance in Candida albicans.

As the investments from the state and society in universities increased rapidly, the scientific and technological resources gained huge promotion. However, the efficiency of some instruments remained low, and the repeated purchases of some instruments occurred frequently. Here the authors discussed about building a practical, reasonable and efficient system for lab management.

The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary (intrinsic) or secondary (acquired) resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fungi.

With the wide use of azoles,drug tolerance and cross tolerance of Candida albicands has seriously hampered the clinical treatments of Candida albicands.New antifungal agents(potent and effective) have been developed over the past years based on the discovery of many new target sites of Candida albicands.For example,Echinocandins(caspofungin and micafungin),aiming at the cell wall of Candida albicands,showed strong antifungal activities to fluconazole resistant candidas and fungal biofilm.Moreover,because ?-glucan synthase does not exist on the cell membrane of mammalian cells,Echinocandins has a low toxicity and a promising clinical future.Though the mechanism of Histatin(targeting fungal membrane) is not clear,it has strong activity not only on candida resistant of polyene and azole,but also to Candida parapsilosis,Candida krusei and Cryptococcus neoformans.Berberine and Ocimum gratissimum L.were also found to have prominent anti-fungi activities.Berberine extract can intensively inhibit 24-SMT in a dose-depended manner;besides,it has more potent inhibitory activity against the growth of mycelia than against that of yeast.Various new methods can be used to increase the susceptibility of Candida albicands to antifungal agents,such as altering fungi membrane composition,changing some genes,adopting the photodynamic inactivation method,employing hypersensitization agents and combining antifungal agents.This article reviews the newly-developed antifungal agents and newly-proposed target sites of Candida albicands.

Purpose To evaluate the relative bioavailability of a domestic sustained-release metformin tablets (SRM) compared against an immediate-release metformin tablets (IRM) using a multiple-dose,two-way crossover design after a single-dose study. Methods Eighteen healthy adult male volunteers,aged 18 to 22 years (mean,20 years),weighing 55 to 76 kg (mean,64 kg) and with height ranging from 166 to 180 cm (mean,173 cm),and blood glucose levels from 4.0 to 5.9 mmol/L (mean,4.3 mmol/L) participated in the study.The concentrations of metformin in plasma were determined using a ion-pair liquid chromatographic method. Results In single-dose study,the mean residence time (MRT),Tmax,and apparent elimination half-life (T1/2) for SRM were significantly longer and Cmax significantly lower than the corresponding values determined for IRM.The similar results were also demonstrated in multiple-dose study.The mean values of the relative bioavaibility of SRM compared with IRM in two administration ways were (85.95±0.97)% and (86.44±7.88)%,respectively.The single-dose and multiple-dose administration of the 90% confidence interval for the ratio of the logarithmic transformed AUC values of SRM over those of IRM were calculated to lie between 0.83 and 0.88,0.83 and 0.89,respectively,being within the acceptable bioequivalence limit of 0.80～1.25. Conclusion SRM was of the characteristic of sustained-release pharmacokinetics.The relative bioavailability for single dosing was similar to that of multiple dosing,and both of the administration ways demonstrated bioequivalence in absorption between SRM and IRM.

Cap1p, encoded by CAP1, is a basic region-leucine zipper (bZip) transcription factor in Candida albicans. It has been proven to play important roles in both drug resistance and oxidative stress. Within the AP-1 family, Cap1p belongs to the same subgroup which also includes Yap1p, Yap2p, and Pap1p. The function of Cap1p is regulated by a nuclear localization mechanism. In recent years, some target genes of Cap1p have been discovered and the differences as well as similarities between Cap1p and Yap1p have been revealed. However, the role of Cap1p in the drug resistance of Candida albicans still needs to be further investigated. Currently drug resistance and oxidative stress are the 2 focuses in the research of fungal pathogens, making Cap1p very important in the future study. The authors have been involved in Cap1p research for a long time and this review introduces the current progress in the area.

Objective:To introduce a "Four-step method" for extraction and separation of Candida albicans total proteins.Methods: Proteins of C.albicans were extracted step-by-step with 4 kinds of solutions with different solubilities.After quantification,the protein samples were separated by isoelectric focusing electrophoresis and then by SDS-PAGE.Results: Proteins with different solubilities were successfully extracted step-by-step from C.albicans and were separated by two-dimensional gel electrophoresis. Conclusion: The "Four-step method" for extraction of C.albicans proteins is an effective approach to study C.albicans membrane proteome and lays a foundation for further investigation of the mechanisms of antifungal agents and drug resistance in C.albicans.

The effects of C1-930, a known selective phosphodiesterase 111 inhibitor, on vascular resistance and rat aortic strip contraction were studied CI-930 025mg/kg injected into the perfused artery, reduced vascular resistance markedly in femoral artery and internal carotid artery in anaesthetized rats. The action lasted for about 15-20 min. CI-930 in vitro inhibited norepinephrine (NE) and TXA2/PGH, mimetic U-46619 induced rat aortic strip contraction significantly with PD, values of 6.71 and 5.5 respectively. The inhibitory effects of CI-930 on NE and U-46619 induced contraction were more potent than that of KG induced contraction. CI-930 0.01 - 10?mol/L exhibited a potential inhibitory effects on intracellular Ca2+ dependent contraction of rat aortic strip induced by NE, but had no effect on extracellular Ca2+ dependent contraction. The results suggest that CI-930 can possess a potent intracellular Ca2+ dependent vasodilating effects in vitro and in vivo.

ATP binding cassette transporter (ABCT),a membrane transporting protein existing in mammalian, bacterial, fungal and many other types of cells, is correlated with multidrug resistance in many cells. To date 10 ABCT have been described in Candida albicans , but only CDR1 and CDR2 genes were associated with multidrug resistance. Moreover, their encoding proteins Cdr1p and Cdr2p have many functions such as efflux pump and phospholipid translocator. The progress in the study of Cdr1p and Cdr2p proteins mediating multidrug resistance in Candida albicans was summarized in the paper.

This paper combines the experience that university is in constructing center of experimental teaching.We thoroughly elaborated center of experimental teaching the guidelines of construction,develop process,and concrete conditions were introduced such as experiment resources integration,instruments management,network construction,personnel dispensation,model of managements establishment,laboratory open,and have obtained the obviously result.