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1.
J Ethnopharmacol ; 246: 112228, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31513838

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong Rhizoma and Cyperi Rhizoma (CRCR), an ancient and classic herbal pair, has been used in herbal medicines for treating migraine, but its effective components are not clear. AIM OF THE STUDY: The present study aimed to identify and quantify the quality markers and anti-migraine active components in CRCR based on chemometric analysis between chemical constituents and pharmacological effects. MATERIALS AND METHODS: The HPLC fingerprints of eight batches of CRCR samples were obtained, and their characteristic common peaks were identified by HPLC-ESI-Q-TOF-MS/MS. The therapeutic effects of eight batches of CRCR samples on nitroglycerin-induced migraine rats were evaluated by migraine-related neurotransmitters and neuropeptides. Similarity analysis, hierarchical cluster analysis and principal component analysis were applied to screen the quality markers. Artificial neural network and partial least squares regression models were used to screen the anti-migraine compounds by correlating the chemical constituents in HPLC fingerprints and pharmacological indicators. RESULTS: Eighteen characteristic common peaks were found in the HPLC fingerprints, including eleven known compounds and seven unknown compounds. Ferulic acid (FA), senkyunolide I (SI), senkyunolide A (SA), 3-n-butylphthalide (NBP), Z-ligustilide (LIG), Z-3-butylidenephthalide (BDPH), nookatone (NKT), levistilide A (LA), α-cyperone (CYP) and other five unknown compounds (P1, P2, P7, P8 and P9) were identified as quality markers. SA, NBP, LIG, NKT, CYP and other three unknown compounds (P1, P4 and P9) can be considered as anti-migraine prototype compounds. The quality markers and anti-migraine active components were further quantified in CRCR extract, rat serum and cerebral cortex by UPLC-MS/MS, which gives a clue to track the dynamic changes of the contents of the main constituents. CONCLUSIONS: Our study explored the anti-migraine material basis, and could lay a foundation for the improvement of the quality control of CRCR in practice.

2.
Pharm Dev Technol ; : 1-36, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31661648

RESUMO

Curcumin, a polyphenol compound extracted from the roots of turmeric plants, possesses anti-depressant effect by regulating the levels of neuroendocrine immunological factors. The purpose of this study was to investigate the anti-depressant effect of curcumin through nasal delivery. The results of phase solubility, Fourier transform infrared spectra, Differential scanning calorimetry, X-ray powder diffractometry and 1H NMR spectra assays showed that curcumin/hydroxypropyl-ß-cyclodextrin complex had been obtained. The viscosity of hydrogel increased rapidly at the temperature range of 29-30 °C through the test of rheological property of Guanidine-Chitosan thermo-sensitive hydrogel. And the hydrogel had good mucoadhesion properties. The cumulative release rate of curcumin was 55% in 10 hours in vitro drug release test. Curcumin-loaded (14.6, 29.2 or 58.4 µg/kg) thermo-sensitive hydrogel could reduce the immobility time of mice in force swimming test and tail suspension test, while could not increase the independent behavioral activity of mice. In addition, curcumin-loaded (14.6, 29.2 or 58.4 µg/kg) thermo-sensitive hydrogel could increase the concentration of Norepinephrine, Dopamine, 5-Hydroxytryptamine and their metabolites in hippocampus and striatum. In conclusion, thermo-sensitive hydrogel delivery system can be seen as a promising formulation of curcumin for the treatment of depression through nasal delivery.

3.
J Clin Lab Anal ; : e23042, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587366

RESUMO

OBJECTIVE: To investigate the correlation of 5-hydroxy tryptamine receptor 6 (5-HTR6) gene polymorphism with vestibular migraine (VM). METHODS: A total of 92 VM patients were enrolled as the observation group, and 100 healthy people receiving physical examinations as the control group. Their general clinical information was collected, and the level of 5-HT in plasma and the vestibular function test indexes were detected. Moreover, the polymorphism of 5-HTR6 rs770963777 was detected with the TaqMan-MGB probe. RESULTS: The observation group had a lower level of 5-HT than the control group (P < .05), and the abnormality rates of the vestibular function tests, including the caloric test, head-shaking test, and vestibular autorotation test, were obviously higher than those in the control group (P < .01). The comparisons showed that the distribution frequencies of the genotypes and alleles were different between the two groups (P < .05). According to the analysis of the genetic mode, there were differences in recessive and additive modes between the two groups (P < .05), but the dominant mode was not different between the two groups (P > .05). CONCLUSION: The level of 5-HT and the vestibular function test indexes can serve as the effective indicators for observing VM, and the polymorphism of 5-HTR6 rs770963777 site is correlated with VM onset.

4.
Sci Rep ; 9(1): 12988, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506482

RESUMO

We propose a high efficiency apodized grating coupler with a bottom reflector for silicon nitride photonic integrated circuits. The reflector consists of a stack of alternate silicon nitride and silicon dioxide quarter-wave films. The design, fabrication and optical characterization of the couplers has been presented. The measured fiber to detector insertion loss was -3.5 dB which corresponds to a peak coupling efficiency of -1.75 dB. A 3 dB wavelength bandwidth of 76.34 nm was demonstrated for the grating coupler with a 20-layer reflector. The fabrication process is CMOS-compatible and requires only a single etching step.

5.
Cancer Control ; 26(1): 1073274819853831, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31480878

RESUMO

BACKGROUND: This study investigates the effect of body mass index (BMI) on complications and satisfaction in patients who underwent thyroidectomy and lateral neck dissection. METHODS: We retrospectively reviewed 386 patients with papillary thyroid cancer who underwent total thyroidectomy and lateral neck dissection between January 2013 and December 2016. We compared variables including population characteristics, subjective satisfaction, and complications in nonobese (BMI < 28.0 kg/m2) and obese (BMI ≥ 28.0 kg/m2) patients. RESULTS: Obesity was associated with an increased risk of postoperative hemorrhage (POH) (P = .014), accessory nerve injury (P < .001), operative time (P < .001) and infection (P = .013). However, obese patients had higher subjective satisfaction and Vancouver Scar Scale (VSS) scores (P < .05). CONCLUSIONS: Obesity was associated with increased risk of POH, injury of the SAN, and infection. Interestingly, we found that obese patients had higher subjective satisfaction and VSS scores.

6.
J Org Chem ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31549831

RESUMO

Five unusual dimers of ent-labdane diterpenoids (1-5) were isolated and identified from Andrographis paniculata, a famous medicinal plant. Bisandrographolide E (1) represents the first example of a labdane dimer possessing an unprecedent tricyclic system that comprised a spiroketal moiety fused with a ketal-γ-lactone unit in its skeleton. Its biosynthetically related intermediates, all four stereoisomers at C-12 and C-15', bisandrographolides F (2, a new compound) and A-C (3-5), were obtained at the same time. The steric configurations of the newly formed asymmetric carbons in 1-5 were first solved by single-crystal X-ray diffraction of the diacetone derivatives of 2-4 and ECD and NMR calculations of 1. More importantly, bisandrographolides 1-5, with different chemical structures or absolute configurations at C-12 and C-15', selectively activated different TRPV1-4 channels and protected cardiomyocytes from hypoxia-reoxygenation injury. Among them, 5 with 12R/15'S configuration activated TRPV1 most effectively and displayed the best cardiomyocyte protection.

7.
Molecules ; 24(18)2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540332

RESUMO

Linarin, a flavone glycoside, is considered to be a promising natural product due to its diverse pharmacological activities. Recently, it has been brought into focus for its potential to treat liver failure. In this study, a rapid and sensitive liquid chromatography electrospray-ionization tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of linarin and its three metabolites (acacetin, apigenin, and p-hydroxy benzaldehyde) in plasma and liver tissue samples of normal rats and rats with d-galactosamine (d-GalN)-induced liver injury. After liquid-liquid extraction (LLE) with ethyl acetate, chromatographic separation of the four analytes was achieved using an ACQUITY UPLC BEH-C18 (1.7 µm, 2.1 × 50 mm) with a mobile phase of 0.01% formic acid in methanol and 0.01% formic acid at a flow rate of 0.3 mL/min. The detection was accomplished on a tandem mass spectrometer via an electrospray ionization (ESI) source by multiple reaction monitoring (MRM) in the negative ionization mode. The method had a good linearity over the concentration range of 1.00-200 ng/mL for linarin and its metabolites. The validated method was successfully applied to the pharmacokinetic and liver tissue distribution study of linarin and its metabolites after a single oral administration of linarin (90 mg/kg) to rats.

9.
Med Sci Monit ; 25: 5929-5933, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395849

RESUMO

BACKGROUND The objective of this study was to detect the level of olfactory function in patients with systemic lupus erythematosus (SLE) and to explore the relationship between impaired olfactory function and anti-ribosomal P protein antibody (ARPA), disease duration, and age. MATERIAL AND METHODS The level of olfactory function in 65 patients with SLE and 50 healthy participants was detected using the Connecticut Chemosensory Clinical Research Center (CCCRC) method; serum ARPA levels in SLE patients and the healthy control group were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS CCCRC scores in the active SLE group was lower than that in the inactive SLE and healthy control groups (P<0.01). In SLE patients, the CCCRC scores of ARPA-positive patients were lower than those of ARPA-negative patients (P<0.01). A negative correlation was discovered between CCCRC scores and ARPA serum levels in SLE patients. Multiple linear regression analyses showed a correlation among the CCCRC score, age, and ARPA. CONCLUSIONS Olfactory dysfunction was found in patients with active SLE; which correlated with SLE disease activity and ARPA levels.

10.
ACS Appl Mater Interfaces ; 11(35): 32373-32380, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31407877

RESUMO

Rechargeable batteries that combine high energy density with high power density are highly demanded. However, the wide utilization of lithium metal anode is limited by the uncontrollable dendrite growth, and the conventional lithium-ion batteries (LIBs) commonly suffer from low rate capability. Here, we for the first time develop a biofilm-coated separator for high-energy and high-power batteries. It reveals that the coating of Escherichia coli protein nanofibers can improve electrolyte wettability and lithium transference number and enhance adhesion between separators and electrodes. Thus, lithium dendrite growth is impeded because of the uniform distribution of the Li-ion flux. The modified separator also enables the stable cycling of high-voltage Li|Li1.2Mn0.6Ni0.2O2 (LNMO) cells at an extremely high rate of 20 C, delivering a high specific capacity of 83.1 mA h g-1, which exceeds the conventional counterpart. In addition, the modified separator in the Li4Ti5O12|LNMO full cell also exhibits a larger capacity of 68.2 mA h g-1 at 10 C than the uncoated separator of 37.4 mA h g-1. Such remarkable performances of the modified separators arise from the conformal, adhesive, and endurable coating of biofilm nanofibers. Our work opens up a new opportunity for protein-based biomaterials in practical application of high-energy and high-power batteries.

11.
J Cancer Res Ther ; 15(4): 882-888, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436247

RESUMO

Objective: T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) has been widely recognized as a negative regulator of antitumor immunity. However, the mechanism by which Tim-3 suppresses antitumor treatment in gliomas remains unclear. This study aims to explore whether Tim-3 is expressed and to evaluate its effect in drug-fasted glioma cells. Subjects and Methods: U87 and U251 glioma cell lines were tested. Cell proliferation activity, cell viability, and the protein and mRNA levels of Tim-3 were detected using CCK-8, flow cytometry, Western blotting, and reverse transcription-quantitative polymerase chain reaction, respectively. Enhancement of the sensitivity of glioma cells to chemotherapeutic agents was tested after inhibiting Tim-3 expression using Tim-3 small interfering RNAs (siRNA). Results: As temozolomide (TMZ) concentration increased, the ratio of apoptotic cells also increased accordingly. However, the level of Tim-3 expression in living cells from the high-dose group was higher than in the low- and middle-dose groups. After interfering with the expression of Tim-3 using siRNA against Tim-3, the killing effect of TMZ rose through an increase in apoptosis. Conclusions: The presence of Tim-3 mRNA and protein in glioma cells was detected. Significantly, knocking down Tim-3 expression improved the potential of TMZ treatment.

12.
Drug Des Devel Ther ; 13: 2357-2370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409970

RESUMO

Purpose: To determine the pharmacokinetic properties and pharmacological activity of the Yougui pill (YGP), which is a well-known Chinese medicine formula. Methods: An ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry via electrospray ionization interface (UPLC-ESI-MS/MS) method was developed and validated for the simultaneous determination of several components in rat plasma. The method was then successfully applied to the pharmacokinetics of six bioactive components in experimental autoimmune encephalomyelitis (EAE) model rats after oral administration of YGP. The expression of cAMP response element binding protein (CREB) and growth-associated protein-43 (GAP-43) in SH-SY5Y cells treated with these six components, YGP extract, and YGP-containing serum were investigated to determine the pharmacodyamic material basis of YGP. Six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside, which were rapidly absorbed after administration in EAE model rats. Results: The main pharmacokinetic parameters of six bioactive components were determined, and the constituents increased CREB and GAP-43 expressions in serum-deprived SH-SY5Y cells. The YGP-containing serum, six bioactive components, and YGP extract significantly increased the expression of both CREB and GAP-43 (P<0.01), and there was no difference between the three groups. Conclusion: The songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside were confirmed as the major bioactive components in YGP. The acquired data will be helpful for understanding the pharmacological and effective constituents of YGP.

13.
Biomed Environ Sci ; 32(7): 531-540, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331437

RESUMO

OBJECTIVE: To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine. METHODS: Mice were immunized intranasally with PBS (negative control), or H3N2 split vaccine (3 µg/mouse) alone, or CTA1-DD (5 µg/mouse) alone, or H3N2 split vaccine (3 µg/mouse) plus CTA1-DD (5 µg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine (3 µg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured. RESULTS: H3N2 split vaccine formulated with CTA1-DD could elicit higher IgM, IgG and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory IgA titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus. CONCLUSION: CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines.


Assuntos
Adjuvantes Imunológicos , Toxina da Cólera , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza , Proteínas Recombinantes de Fusão , Administração Intranasal , Animais , Feminino , Imunidade Humoral , Camundongos Endogâmicos BALB C , Mucosa Nasal/imunologia , Distribuição Aleatória
14.
Curr Med Chem ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31309877

RESUMO

BACKGROUND: The development of modern nanomedicine greatly relies on the involvement of novel materials as drug delivery system. In order to maximize the therapeutic effects of drugs and minimize their side effects, many kinds of natural or synthetic materials have been widely investigated for drug delivery. Among these materials, biomimetic self-assembling peptides (SAPs) have received more and more attentions in recent years. Considering the rapidly growing number of SAPs designed for drug delivery, a summary of how SAPs-based drug delivery systems were designed would be beneficial. METHOD: We overviewed research works on different SAPs that have been investigated as carriers for different drugs, focusing on the design of SAPs nanomaterials and how they were used for drug delivery in different strategies. RESULTS: Based on the principle rules of chemical complementarity and structural compatibility, SAPs such as ionic self-complementary peptide, peptide amphiphile and surfactant-like peptide could be designed. Determined by the features of peptide materials and the drugs to be delivered, different strategies such as hydrogel embedding, hydrophobic interaction, electrostatic interaction, covalent conjugation or the combination of them could be employed to fabricate SAPs-drug complex, which could achieve slow release, targeted or environment-responsive delivery of drugs. Furthermore, some SAPs could also be combined with other types of materials for drug delivery, or even act as drug by themselves. CONCLUSION: Various types of SAPs have been designed and used for drug delivery following various strategies, suggesting that SAPs as a category of versatile nanomaterials have promising potential in the field of nanomedicine.

15.
Acta Pharmacol Sin ; 40(10): 1364-1372, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31253939

RESUMO

Arthrobacter globiformis Uricase (AgUricase) is a homotetrameric uricase with the potential for therapeutic use in treating hyperuricemia-related diseases. To achieve sufficient therapeutic effects, it is essential for this enzyme to have high thermostability and long half-life in physiological condition. To improve the thermostability of this enzyme, we introduced a series of cysteine pair mutations into the AgUricase subunits based on its structural model and studied the thermostability of the mutant enzymes with introduced disulfide bridges. Two intersubunit cysteine pair mutations, K12C-E286C and S296C-S296C, were found to markedly increase the melting temperatures of the corresponding mutant enzymes compared with WT AgUricase. The crystal structure of the K12C-E286C mutant at 1.99 Å resolution confirmed the formation of a distinct disulfide bond between the two subunits in the dimer. Structural analysis and biochemical data revealed that the C-terminal loop of AgUricase was flexible, and its interaction with neighboring subunits was required for the stability of the enzyme. We introduced an additional intersubunit K244C-C302 disulfide bond based on the crystal structure of the K12C-E286C mutant and confirmed that this additional disulfide bond further stabilized the flexible C-terminal loop and improved the thermostability of the enzyme. Disulfide cross-linking also protected AgUricase from protease digestion. Our studies suggest that the introduction of disulfide bonds into proteins is a potential strategy for enhancing the thermostability of multimeric proteins for medical applications.

16.
Asia Pac J Clin Nutr ; 28(2): 246-251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192553

RESUMO

BACKGROUND AND OBJECTIVES: The participation of a nutrition support pharmacist (NSP) in a multidisciplinary team (MDT) for patients receiving nutrition support therapy (NST) may lead to more favourable outcomes and fewer complications and adverse events. However, few studies have demonstrated the role of NSPs in MDTs in China. To investigate pharmacy interventions and physician acceptance of these interventions for patients receiving NST in an intensive care unit (ICU). METHODS AND STUDY DESIGN: A prospective study over a 12-month period was conducted in an ICU at an academic hospital in China. Interventions were documented and divided into the following categories: indication of NST, parenteral nutrition (PN) prescription and delivery, enteral nutrition (EN) route and formulation, fluids and electrolytes, laboratory test monitoring, nutritional supplements, and other medication-related problems. Data regarding the intervention categories, timing, acceptance rates, and methods of communication to discuss pharmacy interventions were collected. RESULTS: In total, 247 interventions for 120 patients were identified. The overall acceptance rate of interventions was 85.0% (210/247), and more than half of the interventions (143, 57.9%) were performed during daily follow-up. The most common intervention categories were PN prescription and delivery (81/247, 32.8%), EN route and formula (33/247, 13.4%), indication of NST (33/247, 13.4%), and nutritional supplements (30/247, 12.1%). The most accepted intervention category was PN prescription and delivery (79/81, 97.5%), and the most common method of communication was oral communication during MDT rounds (201/247, 81.4%). CONCLUSIONS: This study demonstrated the unique perspectives offered and importance of having pharmacists as members of MDTs.

17.
Environ Res ; 176: 108530, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220737

RESUMO

This study enrolled 3266 pregnant women, to explore the relationship of prenatal phthalate exposure with the risk of preterm birth and gestational age. All participants filled questionnaires and provided with up to three urine samples during three trimesters. Seven phthalate metabolites in urines were measured. The incidences of very preterm, late preterm, early-term, late-term and postterm births were 0.58%, 3.52%, 24.22%, 10.53%, and 0.34%, respectively. Non-linear relationships were shown between phthalate metabolites and gestational age. Except for monomethyl phthalate (OR = 1.65, 95%CI = 1.17-2.34), the average concentrations of phthalate metabolites were associated with a slightly and insignificantly increased risk of overall preterm birth (<37+0 gestational weeks). Through a restricted cubic spline regression, phthalate metabolites were found to be related to the risk of overall preterm birth in a linear manner (p-value >0.05) or a non-linear manner (p-value <0.05). All curves indicated the overall preterm birth risk rose with the increase of phthalate metabolite concentrations. Finally, compared with full-term birth (39+0 to 40+6 gestational weeks), phthalate metabolites were associated with the elevated risks of very preterm, late preterm and postterm births, although some relationships were not statistically significant. In conclusion, these findings suggested non-linear associations between phthalate metabolites and gestational age. Exposure to some phthalate metabolites was associated with increased risks of overall preterm birth and postterm birth.

18.
J Sep Sci ; 42(16): 2592-2601, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31161707

RESUMO

A rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed and validated for simultaneous determination of puerarin, daidzin, daidzein, 3'-hydroxy puerarin, and genistein in rat plasma after oral administration of Puerariae lobatae radix extract. The method of protein precipitation with acetonitrile was used for sample preparation. Chromatographic separation was achieved on a C18 column with the mobile phases of acetonitrile/water containing 0.1% formic acid. The analytes were detected by mass spectrometer with an electrospray ionization source operating in the negative ion mode. The linearity, precision, accuracy, dilution reliability, recovery, matrix effects, and stability of the method were within acceptable ranges. The developed method was successfully used to compare the pharmacokinetic characteristics of five analytes in normal and type 2 diabetics rats after oral administration of Puerariae lobatae radix extract. Several pharmacokinetic alterations were observed and this might be caused by the pathological state of type 2 diabetes.

19.
Theranostics ; 9(11): 3293-3307, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244955

RESUMO

The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O2) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O2 sustainably through the Fenton reaction. In contrast to traditional strategies that increase O2 based on decomposition of limited concentration of hydrogen peroxide (H2O2), our methodology could maintain the concentration of H2O2 and O2 through the Fenton reaction. Methods: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both in vitro and in vivo. Results: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O2 concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. Conclusion: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.

20.
J Am Heart Assoc ; 8(12): e012355, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31165666

RESUMO

Background Readmission rates are a widely accepted quality indicator. Our objective was to develop models for calculating case-mixed adjusted readmission rates after transcatheter aortic valve replacement for the purpose of profiling hospitals. Methods and Results In this population-based study in Ontario, Canada, we identified all transcatheter aortic valve replacement procedures between April 1, 2012, and March 31, 2016. For each hospital, we first calculated 30-day and 1-year risk-standardized (predicted versus expected) readmission rates, using 2-level hierarchical logistic regression models, including clustering of patients within hospitals. We also calculated the risk-adjusted (observed versus expected) readmission rates, accounting for the competing risk of death using a Fine-Gray competing risk model. We categorized hospitals into 3 groups: those performing worse than expected, those performing better than expected, or those performing as expected, on the basis of whether the 95% CI was above, below, or included the provincial average readmission rate respectively. Our cohort consisted of 2129 transcatheter aortic valve replacement procedures performed at 10 hospitals. The observed readmission rate was 15.4% at 30 days and 44.2% at 1 year, with a range of 10.9% to 21.7% and 38.8% to 55.0%, respectively, across hospitals. Incorporating the competing risk of death translated into meaningful different results between models; as such, we concluded that the risk-adjusted readmission rate was the preferred metric. On the basis of the 30-day risk-adjusted readmission rate, all hospitals performed as expected, with a 95% CI that included the provincial average. However, we found that there was significant variation in 1-year risk-adjusted readmission rate. Conclusions There is significant interhospital variation in 1-year adjusted readmission rates among hospitals, suggesting that this should be a focus for quality improvement efforts in transcatheter aortic valve replacement.

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