Diagnosing Balamuthia mandrillaris amebic meningoencephalitis in a 64-year-old woman from the Southwest of China.

Balamuthia mandrillaris amebic encephalitis (BAE) can cause a fatal condition if diagnosis is delayed or effective treatment is lacking. Patients with BAE have been previously reported in 12 provinces of China, with skin lesions being the primary symptom and encephalitis developing after several years. However, a significantly lower number of cases has been reported in Southwest China. Here we report an aggressive BAE case of a 64-year-old woman farmer with a history of skin lesions on her left hand. She was admitted to our hospital due to symptoms of dizziness, headache, cough, vomiting, and gait instability. She was initially diagnosed with syphilitic meningoencephalitis and received a variety of empirical treatment that failed to improve her symptoms. Finally, she was diagnosed with BAE combined with amebic pneumonia using next-generation sequencing (NGS), qRT-PCR, sequence analysis, and imaging studies. She died approximately 3 weeks after the onset. This case highlights that the rapid development of encephalitis can be a prominent clinical manifestation of Balamuthia mandrillaris infection.

Upregulation of microRNA-1270 suppressed human glioblastoma cancer cell proliferation migration and tumorigenesis by acting through WT1.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors among human beings. In this study, we explored the functions of human microRNA-1270 (hsa-miR-1270) on GBM cancer cell proliferation, migration, and tumorigenesis. MATERIALS AND METHODS: In GBM cell lines and clinical tissues, hsa-miR-1270 expression was probed by quantitative real-time PCR (qRT-PCR). In LN-18 and A172 cells, hsa-miR-1270 was upregulated by lentiviral transduction. The effects of hsa-miR-1270 upregulation on GBM in vitro and in vivo functions were probed by proliferation, migration, and xenograft assays, respectively. The correlation between hsa-miR-1270 and Wilms' tumor gene (WT1) was probed by dual-luciferase activity assay, qRT-PCR, and Western blot. WT1 was then secondarily over-expressed in hsa-miR-1270-upregulated LN-18 and A172 cells, to explore its mechanisms in GBM's association with hsa-miR-1270. RESULTS: Hsa-miR-1270 was significantly downregulated in both GBM cell lines and clinical tumors. Upregulating hsa-miR-1270 considerably suppressed GBM cell proliferation and migration in vitro and xenograft in vivo. WT1 was inversely correlated with hsa-miR-1270 in GBM. WT1 overexpression in hsa-miR-1270-upregulated GBM cells reversed the anticancer functions of hsa-miR-1270 on cancer proliferation and migration. CONCLUSION: Hsa-miR-1270 upregulation may have suppressing effects on GBM cancer cells, likely by functionally acting through WT1.

Extruded Polystyrene Foams with Enhanced Insulation and Mechanical Properties by a Benzene-Trisamide-Based Additive.

Low thermal conductivity and adequate mechanical strength are desired for extruded polystyrene foams when they are applied as insulation materials. In this study, we improved the thermal insulation behavior and mechanical properties of extruded polystyrene foams through morphology control with the foam nucleating agent 1,3,5-benzene-trisamide. Furthermore, the structure⁻property relationships of extruded polystyrene foams were established. Extruded polystyrene foams with selected concentrations of benzene-trisamide were used to evaluate the influence of cell size and foam density on the thermal conductivity. It was shown that the addition of benzene-trisamide reduces the thermal conductivity by up to 17%. An increase in foam density led to a higher compression modulus of the foams. With 0.2 wt % benzene-trisamide, the compression modulus increased by a factor of 4 from 11.7 ± 2.7 MPa for the neat polystyrene (PS) to 46.3 ± 4.3 MPa with 0.2 wt % benzene-trisamide. The increase in modulus was found to follow a power law relationship with respect to the foam density. Furthermore, the compression moduli were normalized by the foam density in order to evaluate the effect of benzene-trisamide alone. A 0.2 wt % benzene-trisamide increased the normalized compression modulus by about 23%, which could be attributed to the additional stress contribution of nanofibers, and might also retard the face stretching and edge bending of the foams.

Chemical Modification and Foam Processing of Polylactide (PLA).

Polylactide (PLA) is known as one of the most promising biopolymers as it is derived from renewable feedstock and can be biodegraded. During the last two decades, it moved more and more into the focus of scientific research and industrial use. It is even considered as a suitable replacement for standard petroleum-based polymers, such as polystyrene (PS), which can be found in a wide range of applications-amongst others in foams for packaging and insulation applications-but cause strong environmental issues. PLA has comparable mechanical properties to PS. However, the lack of melt strength is often referred to as a drawback for most foaming processes. One way to overcome this issue is the incorporation of chemical modifiers which can induce chain extension, branching, or cross-linking. As such, a wide variety of substances were studied in the literature. This work should give an overview of the most commonly used chemical modifiers and their effects on rheological, thermal, and foaming behavior. Therefore, this review article summarizes the research conducted on neat and chemically modified PLA foamed with the conventional foaming methods (i.e., batch foaming, foam extrusion, foam injection molding, and bead foaming).

Accuracy of neutrophil CD64 expression in diagnosing infection in patients with autoimmune diseases: a meta-analysis.

We aimed to systematically evaluate the accuracy of nCD64 in diagnosing infection in patients with autoimmune diseases. Studies were searched in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases up to October 2018. There was no restriction for language and age. Prospective studies examining the accuracy of nCD64 in diagnosing infection in patients with autoimmune diseases were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of eligible studies. Stata 15.1 and Meta-DiSc 1.4 software were used for data analysis. Eleven studies fulfilled the inclusion criteria (677 patients, 229 patients with bacterial infection, and 448 without infection). The pooled sensitivity and specificity of nCD64 were 89% (95% confidence interval (CI) 82-93) and 94% (95% CI 91-96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 14.9 (95% CI 9.3-23.8) and 0.12 (95% CI 0.07-0.20), respectively. The diagnostic odds ratio and area under the summary receiver operating characteristic curve were 123 (95% CI 53-283) and 0.97 (95% CI 0.95-0.98), respectively. The univariate meta-regression analysis showed that region, type of disease, antibiotic therapy, and presentation of nCD64 measurement results were responsible for the heterogeneity. The Deeks' funnel plot asymmetry test showed that there was no publication bias (p = 0.15). nCD64 has a good overall diagnostic performance for differentiating infection from disease flare in patients with autoimmune diseases. Further studies are needed to confirm the optimized cutoff value.

[Correlation between in vitro release and in vivo absorption of sustained-releasing tablets of neostigmine bromide].

OBJECTIVE: To determine the correlation between in vitro release and in vivo absorption of sustained-releasing tablets of neostigmine bromide. METHODS: Water was used as dissolution medium to measured in vitro release of neostigmine bromide. After a single oral administration of 100 mg neostigmine bromide to rabbits, the plasma concentrations of neostigmine bromide in the rabbits were determined by HPLC. The compartment model and deconvolution method were employed to explain the in vitro-in vivo correlation. RESULTS: Using Y as cumulative in vitro release and Fa as percentage of absorption, the regression equation was established: Fa = 0.9298Y + 4.6074, r = 0.9961. The input function of R = 2.0163Y-11.242,r = 0.9270. CONCLUSION: The correlation between in vitro release and in vivo absorption of neostigmine bromide is good.

A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics.

The supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca(2+) accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM.

An optimized molecular inclusion complex of diferuloylmethane: enhanced physical properties and biological activity.

OBJECTIVE: The purpose of this study was to explore and evaluate the enhanced physical properties and biological activity of a molecular inclusion complex (MICDH) comprising diferuloylmethane (DFM) and hydroxypropyl-ß-cyclodextrin. METHODS: The preparation conditions of MICDH were optimized using an orthogonal experimental design. The solubility, in vitro release and model fitting, microscopic morphology, molecular structure simulation, anti-lung cancer activity, and action mechanism of MICDH were evaluated. RESULTS: The solubility of DFM was improved 4400-fold upon complexation with hydroxypropyl-ß-cyclodextrin. The release rate of DFM was significantly higher from MICDH than from free DFM. MICDH exhibited higher antitumor activity against human lung adenocarcinoma A549 cells than free DFM. More cells were arrested in the S/G2 phase of the cell cycle or were induced to undergo apoptosis when treated with MICDH than when treated with free DFM. Furthermore, increased reactive oxygen species and intracellular calcium ion levels and decreased mitochondrial membrane potential were observed in cells treated with MICDH. CONCLUSION: MICDH markedly improved the physical properties and antitumor activity of DFM. MICDH may prove to be a preferred alternative to free DFM as a formulation for DFM delivery in lung cancer treatment.

Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes.

OBJECTIVE: Previous studies on various enzymosomes (functional lipid vesicles encapsulating an enzyme) have been mostly carried out in vitro and have focused on preserving catalytic activity and improving the stability of the enzyme. Until now, few studies have focused on their in vivo fate. Similarly, although we have previously reported the increased in vitro uricolytic activity (about 2.2 times higher than that of free uricase, or three times higher than that of PEGylated uricase, Puricase(®), under physiological pH and temperature) and improved stability of the novel alkaline enzymosomes (functional lipid vesicles encapsulating uricase from Candida utilis: uricase-containing lipid vesicles, UOXLVs), it is still necessary to study the biological properties and hypouricemic effects of UOXLVs in vivo. METHODS: The enzyme kinetics, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary safety of UOXLVs were evaluated. RESULTS: The Michaelis constant (K(m)) value of the UOXLVs was slightly lower than that of the free enzyme. The enzyme release from the UOXLVs lasted over 12 hours and their circulation half-life was about sevenfold longer than that of the free uricase. Meanwhile, the UOXLVs had a 22-fold increase in the area under the curve compared with the free uricase. Furthermore, it took less than 3 hours for the UOXLVs to lower the plasma uric acid concentration from a high to a normal level, compared with 6 hours for the free uricase. In addition, the UOXLVs had much less immunogenicity than free uricase and were well tolerated by all animals throughout the observation period. CONCLUSION: The UOXLVs markedly improved the biological properties and enhanced the hypouricemic effects of uricase in vivo.

Uricase from Bacillus fastidious loaded in alkaline enzymosomes: enhanced biochemical and pharmacological characteristics in hypouricemic rats.

The aim of this study was to assess the potential of a novel alkaline enzymosome to deliver uricase from Bacillus fastidious (UBF) and enhance its biochemical and pharmacological characteristics. The in vitro catalytic activity of the UBF loaded in the novel alkaline enzymosomes (ESUBFs) was almost 3.8 times that of free UBF at the optimum pH or 1.5 times that of free UBF at the physiological pH. Following intravenous (i.v.) administration (2000 mU/kg) in rats, ESUBFs provided significantly higher (22.5-fold) area under the plasma concentration (AUC) and longer (8.2-fold) circulation half-life (t(1/2)) compared with free UBF, respectively. Further, it took only 4.5h (or 1.1h) for ESUBFs to lower the plasma uric acid concentration from a high level to the normal level of rat (or human beings), compared with 7.6h (or 5.4h) for free UBF. Our results showed that ESUBFs could efficiently deliver UBF and favorably modify its biochemical and pharmacological characteristics by increasing the AUC, t(1/2), and catalytic activity. Therefore, ESUBFs might be a preferred alternative to cure hyperuricemia and gout.

[Pharmacokinetic study of a new chewing gum dextromethorphan delivery system].

OBJECTIVE: To establish an high-performance liquid chromatography (HPLC)-based method for analysis of the pharmacokinetics and relative bioavailability of dextromethorphan chewing gum tablets in rabbits. METHODS: The pharmacokinetic parameters and the relative bioavailability of dextromethorphan chewing gum preparation in rabbits were compared with those of the commercially available chewing dextromethorphan tablets using 3P97 software. RESULTS: Pharmacokinetic analysis of the new dextromethorphan chewing gum tablets showed a AUC of 488.76 ∓ 175.00 ng.ml(-1).h, C(max) of 95.45 ∓ 17.53 ng/ml, and t(max) of 1.83 ∓ 0.57 h as compared with the corresponding parameters of 370.13 ∓ 90.56 ng.ml(-1).h, 174.00 ∓ 47.88 ng.ml, and 1.04 ∓ 0.14 h for the commercially available chewing tablets. The relative bioavailability of the new chewing gum medicine system was (140.73 ∓ 65.91)%. CONCLUSION: The new dextromethorphan chewing gum preparation shows an increased AUC((0→)), decreased C(max), and prolonged t(max) in comparison with the commercially available chewing tablets, with also a greatly enhanced relative bioavailability.