Synergistic antifungal effects and mechanisms of amantadine hydrochloride combined with azole antifungal drugs on drug-resistant Candida albicans

IntroductionThe increasing resistance of Candida albicans (C. albicans) to conventional antifungal drugs poses a great challenge to the clinical treatment of infections caused by this yeast. Drug combinations are a potential therapeutic approach to overcome the drug- resistance of C. albicans. This study explored the synergistic effects of amantadine hydrochloride (AMH) combined with azole antifungal drugs against drug-resistant C. albicans in vitro and in vivo.MethodsThe in vitro sensitivity of Candida spp. to drugs was determined by the microdilution method. The effect of drugs on the efflux pump activity of C. albicans was determined by the rhodamine 6G tracer method. The egg yolk agar plate method was used to determine the activity of extracellular phospholipase, a C. albicans virulence factor. The Galleria mellonella model of C. albicans infection was used to test the in vivo efficacy of the combination therapy.ResultsIn vitro experiments showed that combinations of AMH with azole antifungal drugs had synergistic antifungal effects on planktonic cells of drug-resistant C. albicans, with fractional inhibitory concentration index values of <0.5. The in vivo synergistic effects and mechanism of drug combinations with AMH were further studied using fluconazole (FLC) as a representative azole antifungal drug. In vivo, G. mellonella larvae were used to evaluate the antifungal efficacy of AMH +FLC. AMH + FLC treatment increased the survival rate of larvae infected with drug-resistant C. albicans and reduced tissue invasion. Studies of the mechanism of synergy showed that AMH inhibited drug efflux pump activity in drug-resistant C. albicans, and that AMH + FLC synergistically inhibited early biofilms and the extracellular phospholipase activity of drug-resistant C. albicans.ConclusionThis study provides strong evidence that combinations of non-antifungal drugs and antifungal drugs can effectively overcome drug-resistant C. albicans infection. Both AMH and FLC are FDA-approved drugs, eliminating concerns about safety. Our findings provide a foundation for further clinical antifungal research

Expression of CD147 and matrix metalloproteinase-11 in colorectal cancer and their relationship to clinicopathological features

Background: This study aimed to investigate the expression of CD147 and MMP-11 in human colorectal cancer (CRC) and to evaluate their clinical significance. Methods: Real-time polymerase chain reaction was used to evaluate CD147 and MMP-11 mRNA level in 56 pairs of fresh CRC samples matched with adjacent normal mucosa. The protein expression of CD147 and MMP-11 in CRC specimens and corresponding normal colorectal mucosa were evaluated by immunohistochemistry on CRC tissue microarrays. Expression and co-localization of these two proteins in human colorectal cancer tissue were also evaluated by laser scanning confocal microscopy. Furthermore, their correlations with clinicopathological factors and overall survival after surgery were evaluated. Results: Both CD147 and MMP-11 were demonstrated to be over-expressed at mRNA level (P < 0.001, both) and protein level (P < 0.001, both) in CRC tissue than paired normal mucosa. Spearman rank test showed a positive correlation between these two proteins (P = 0.025). Immunofluorescence double staining confirmed the co-localization of CD147 and MMP-11 in paraffin-embedded tissues of CRC patients. Expression of CD147 and MMP-11 were both correlated with CRC lymph node metastasis (P = 0.021 and P = 0.031, respectively), distant metastasis (P < 0.001 and P = 0.013, respectively) and TNM stage (P = 0.006 and P = 0.049, respectively). Univariate survival analysis showed that both CD147 and MMP11 expression was significantly associated with shorter survival time (P = 0.001 and P = 0.009, respectively). Additionally, in multivariate analysis, both CD147 and MMP-11 were proved to be independent prognostic factors (P = 0.009, 0.028, respectively). Conclusions: These results indicated that both CD147 and MMP-11 may be involved in the progression of colorectal cancer, and they are potential prognostic factors and might become new therapeutic targets for CRC patients.International Science & Technology Cooperation Program of China [2013DFG32720]; Beijing Municipal Natural Science Foundation [7153161]; National natural science funding [81441071, 61372028, 81272765]; Capital characteristic clinical application research [Z121107001012083]SCI(E)[email protected]

An indole-derived porous organic polymer for the efficient visual colorimetric capture of iodine in aqueous media <i>via</i> the synergistic effects of cation–π and electrostatic forces

A recyclable indole-based POP was successfully achieved, which was capable of visual colorimetric iodine capture in water via cation–π and electrostatic interactions.</p

Lithostratigraphy, mineralogy and the boron-bearing brine evolution of DaQaidam Salt Lake in Qaidam Basin since Holocene period, northern Qinghai-Tibet Plateau

Little attention has been paid to the study of sedimentary records from DaQaidam Salt Lake regarding brine evolution and hydro-climate change. Here we report the results of AMS 14C dating and mineralogical investigation on a sediment profile D4 from the south central of perennial saline water-body. The result revealed that pinnoite deposit in the lakebed was formed in early Holocene, the lake underwent three stages of lake-level and brine evolution in Holocene period, which were determined mainly by precipitation-controlled catchment inflow. The mineralogical records also depicted fluctuations in lake level and hydrochemistry on decadal and centennial scales

The dust storm events recorded in DaQaidam region of Qaidam Basin since Late Glacial period: evidence from the grain size of lake sediment

The paper focused on the study of detrital yellow layer from sediment profile D3 of DaQaidam Salt Lake, based on AMS 14C chronologic and mineralogical methods, aimed to discuss the dust storm events recorded by detrital yellow layer of DaQaidam region since Late Glacial period. The results showed that the grain-size distribution curve displayed double kurtosis, the main peak (10 µm in average) reflected the fine-grained fractions into lake by fluviation, and the secondary peak (&gt; 32 µm) reflected the coarse silt fractions into lake by wind effect and fluviation. Finally, the coarse-grained fractions (&gt; 64 µm) from sediment profile D3 probably recorded the dust storm events since Late Glacial period.</jats:p

Distribution and health risks of aerosol black carbon in a representative city of the Qinghai-Tibet Plateau

Although aerosol black carbon (BC) exerts strong influences on human health, research on potential health risks of aerosol BC around the Qinghai-Tibet Plateau is very limited. This is the very first study to investigate the distribution of aerosol BC in a typical city of the Qinghai-Tibet Plateau and the resulting health risks. The results showed that the maximal real-time (5-min monitoring interval) concentration of aerosol BC was 22.34 pg/m 3 , much higher than day- and week-averaged concentrations which were in the range of 1.28-6.15 and 1.93-4.63 gg/m 3 , respectively. The health risks were evaluated using four different health endpoints including low birth weight (LBW), percentage lung function decrement of school-aged children (PLFD), cardiovascular mortality (CM), and lung cancer (LC). The highest risks of LBW, PLFD, CM, and LC had reached 69.5, 184.4, 67.4, and 31.8 numbers of equivalent passively smoked cigarettes (PSC), respectively. The concentrations and health risks of aerosol BC in the study area are at a middle level among the global cities/regions. In comparison, the cities of the Qinghai-Tibet Plateau are experiencing high potential health risks resulting from aerosol BC to need more effective prevention and control of air pollution