Optimization of the Preparation Conditions of Borneol-Modified Ginkgolide Liposomes by Response Surface Methodology and Study of Their Blood Brain Barrier Permeability.

Ginkgolides (GG), containing ginkgolide A (GA), ginkgolide B (GB) and ginkgolide C (GC), are mainly prescribed for ischemic stroke and cerebral infarction. However, the ginkgolides can hardly pass the blood-brain barrier (BBB) into the brain. The purpose of this study was to prepare borneol-modified ginkgolides liposomes (GGB-LPs) to study whether borneol could enhance the transport of ginkgolides across the BBB. The preparation conditions of GGB-LPs were optimized by a response surface-central composite design. Also, pharmacokinetics and biodistribution studies of GGB-LPs were conducted using UPLC-MS. The optimal preparation conditions for GGB-LP were as follows: ratio of lipid to drug (w/w) was 9:1, ratio of phospholipid to cholesterol (w/w) was 7:1, and hydrate volume was 17.5 mL. Under these conditions, the GGB-LP yield was 89.73 ± 3.45%. With GGB-LPs, borneol significantly promoted the transport of ginkgolide across the BBB. The pharmacokinetic parameters of GGB-LP were significantly improved too, with Tmax of 15 min and a high drug concentration of 3.39 µg/g in brain. Additionally, the drug targeting index and relative uptake rate of GGB-LP was increased. Borneol-modified ginkgolide liposomes can thus potentially be used to improve the BBB permeability of gingkolide formulations.

Enhancing the photodynamic effect of curcumin through modification with TiO2 nanoparticles and cationic polymers.

Curcumin (CUR), a natural compound extracted from turmeric, has shown potential as a photosensitizer in photodynamic therapy (PDT). The aim of this work was to enhance the efficacy of CUR by modifying it using titanium dioxide (TiO2) nanoparticles and a cationic polymer called Sofast to create a nanocomposite TiO2-CUR-Sofast (TCS). Compared to unmodified CUR, TCS exhibited a broadening toward longer wavelength in the absorption wavelength within the 400-550 nm range, leading to improved CUR absorption. Cellular uptake efficiency of TCS was also enhanced, and it demonstrated nearly 4.7-fold higher reactive oxygen species (ROS) generation than CUR. Furthermore, TCS displayed the ability to attach to the cell membrane and enter cells within a 30-min incubation period. Upon irradiation, TCS exhibited remarkable cytotoxicity, resulting in a significant reduction in the viability of various cancer cells. Autofluorescence lifetime imaging of intracellular reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) enzymes indicated that cancer cells treated with TCS and irradiation undergo a metabolic pathway shift from oxidative phosphorylation to glycolysis. These findings highlight the potential of TCS as an effective PDT agent for cancer treatment.

Effect of sodium hyaluronate-arboxycellulose membrane (Seprafilm®) on postoperative small bowel obstruction: A meta-analysis.

BACKGROUND: This meta-analysis was performed to evaluate the effect of Seprafilm® on postoperative small bowel obstruction. METHODS: A literature search was conducted in the PubMed and EMBASE databases through August 2020. The pooled risk ratios as well as the corresponding 95% confidence intervals were calculated using RevMan 5.3 software. RESULTS: A total of 9 clinical control trials involving 4,351 patients (2,123 in the Seprafilm® group and 2,228 in the control group) were included. The overall analysis showed that the pooled risk ratio was 0.45 (95% confidence interval = 0.34-0.60; P < .00001), indicating that the risk of postoperative small bowel obstruction can be significantly decreased by the application of Seprafilm®. Similarly, an obvious effect of Seprafilm® on reducing the rate of postoperative small bowel obstruction was also shown in the subgroup analyses by population (adult participants), study design (randomized control study or nonrandomized control study), region (Japan or Korea), follow-up duration (2 years or 5 years), and sheet number of Seprafilm® (1 sheet or >1 sheet). CONCLUSION: In conclusion, the use of Seprafilm® is beneficial for decreasing the rate of postoperative small bowel obstruction.

Single-cell RNA-seq reveals functionally distinct biomaterial degradation-related macrophage populations.

Macrophages play crucial roles in host tissue reaction to biomaterials upon implantation in vivo. However, the complexity of biomaterial degradation-related macrophage subpopulations that accumulate around the implanted biomaterials in situ is not fully understood. Here, using single cell RNA-seq, we analyze the transcriptome profiles of the various cell types around the scaffold to map the scaffold-induced reaction, in an unbiased approach. This enables mapping of all biomaterial degradation-associated cells at high resolution, revealing distinct subpopulations of tissue-resident macrophages as the major cellular sources of biomaterial degradation in situ. We also find that scaffold architecture can affect the mechanotransduction and catabolic activity of specific material degradation-related macrophage subpopulations in an Itgav-Mapk1-Stat3 dependent manner, eventually leading to differences in scaffold degradation rate in vivo. Our work dissects unanticipated aspects of the cellular and molecular basis of biomaterial degradation at the single-cell level, and provides a conceptual framework for developing functional tissue engineering scaffolds in future.

Doxorubicin loaded liposomes for lung tumor targeting: in vivo cell line study in human lung cancer.

PURPOSE: In the present investigation the hydrophilic drug doxorubicin (DOX) was successfully incorporated with the drug carrier GE11 which serves as marker for tumor cells in non small cell lung cancer(NSCLC) to form the liposomal formulation. METHODS: The formulation was fabricated in two steps: one being the preparation of liposomal formulation using reverse phase evaporation method and second is synthesis of DSPE-PEG 2000 - GE 11complex. RESULTS: Thus prepared liposomes when evaluated via scanning electron spectroscopy showed smooth and spherical surface with particle size ranging between 102±0.3 to 120±0.5 nm. The percent encapsulation efficiency was 65.34 with highest drug release of 98% up to 45 h. The cytotoxic study revealed the non-toxic nature of carrier protein (i.e. GE11). The microbiological study has shown the antibiotic efficiency of liposomal formulation to be comparable with pure drug. In vivo cellular uptake study showed efficiency of GE11 protein in accumulation in tumor cells. The study conducted in mice showed more reduction in tumor size with liposomal formulation (312 mm3) than with pure drug (540 mm3). CONCLUSION: DOX loaded liposomes with GE11 as carriers were successfully formulated by using reverse phase evaporation method. The prepared liposomal formulation was found to be most effective in combating cancer cells when compared to pure drug.

Short-term effects of extreme meteorological factors on childhood hand, foot, and mouth disease reinfection in Hefei, China: A distributed lag non-linear analysis.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a major public health issue in China with a high burden of reinfection. Previous studies presented evidence of the relationship between meteorological factors and HFMD incidence, but no study examined the effects of extreme meteorological factors on HFMD reinfection. METHODS: Daily HFMD reinfection counts and meteorological data of Hefei city were collected from 2011 to 2016. A distributed lag non-linear model was used to quantify the effects of extreme weather (wind speed, sunshine duration, and precipitation) on HFMD reinfection. All effects were presented as relative risk (RR), with 90th or 10th percentiles of meteorological variables compare with their median values. Confounding factors, such as mean temperature, relative humidity, day of week, and long-term trend were controlled. RESULTS: A total of 4873 HFMD reinfection cases aged 0-11 years were reported. Extremely high precipitation, low wind speed, and low sunshine duration increased HFMD reinfection risk. The effect of extremely high precipitation was greatest at 8 days lag (RR = 1.01, 95%CI: 1.00-1.02). Extremely low wind speed and low sunshine increased 19% (RR = 1.19, 95%CI: 1.09-1.32) and 12% (RR = 1.12, 95%CI: 1.00-1.26) risk at lag 0-12 days, respectively. By contrast, extremely high wind speed and high sunshine duration exerted certain protective effects on HFMD reinfection at lag 0-12 days (RR = 0.76, 95%CI: 0.66-0.88; RR = 0.88, 95%CI: 0.79-0.99, respectively). Subgroup analyses showed that nursery children were the most sensitive people to the extreme wind speed and sunshine duration. Children aged 4-11 years appeared to be more susceptible to extreme sunshine duration than children aged <3 years. CONCLUSION: The present study provides evidence that extreme meteorological factors exert delayed effects on HFMD reinfection. Developing an early warning system is necessary for the protection of children from harm due to extreme meteorological factors.

Effects of relative humidity on childhood hand, foot, and mouth disease reinfection in Hefei, China.

BACKGROUND: In recent years, hand, foot, and mouth disease (HFMD) has become a major public health issue in China, and its reinfection rate has been high. Numerous studies have examined the effects of meteorological factors involved in HFMD infection. However, no study has investigated the effects on HFMD reinfection. The present study analyzed the relationship between relative humidity and HFMD reinfection. METHODS: We employed a distributed lag nonlinear model to evaluate the relationship between relative humidity and childhood HFMD reinfection in Hefei, China during 2011-2016. This model controlled confounding factors, including seasonality, long-term trend, day of the week, precipitation, and mean temperature. RESULTS: Childhood HFMD reinfection cases occurred mainly from April to July, and the second peak occurred from October to December. A statistically significant association was observed between relative humidity and HFMD reinfection with delayed effects. The adverse effect of high relative humidity (>75%) appeared later than those of low relative humidity (<75%). Moreover, the highest relative risk (RR 1.08, 95% CI 1.04-1.13) occurred when the relative humidity was 100% and had an 8-day lag. Given the differences between gender and age groups, the effects of extremely high relative humidity on females and those aged ≥4years were higher than those of other groups and caused the highest cumulative relative risks at lag 0-9 or 0-10days (Female: RR 2.00, 95% CI 1.23-3.26; Male: RR 1.55, 95% CI 1.04-2.30; Aged ≥4years: RR 2.31, 95% CI 1.27-4.18; Aged <4years: RR 1.51, 95% CI 1.04-2.20). CONCLUSION: High and low relative humidity were found to cause the elevated risks of HFMD reinfection, and the highest risk was observed at extremely high relative humidity. Early warning systems should be built for the protection of susceptible populations, particularly females and children aged ≥4years.