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1.
J Dairy Sci ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32229112

RESUMO

The objective of this study was to evaluate the protection conferred by lactoferrin, α-lactalbumin, and ß-lactoglobulin in cerebral ischemia reperfusion (I/R) injury. Rat pheochromocytoma (PC12) cells were used to construct an oxygen and glucose deprivation model in vitro, and ICR mice underwent carotid artery "ligation-relaxation" to construct a cerebral I/R injury model in vivo. The level of toll-like receptor 4 (TLR4) and downstream factors including nuclear factor-κB, tumor necrosis factor-α, and IL-1ß were measured. Metabonomics detection and data mining were conducted to identify the specific metabolic sponsor of the 3 proteins. The results showed that lactoferrin, α-lactalbumin, and ß-lactoglobulin protected neurons from cerebral I/R injury by increasing the level of bopindolol and subsequently inhibiting the TLR4-related pathway to different degrees; ß-lactoglobulin had the strongest activity of the 3 proteins. In summary, this study is the first to investigate and compare the protective effects of lactoferrin, α-lactalbumin, and ß-lactoglobulin in a cerebral stroke model. The results implicate TLR4 as a novel target of the 3 bioactive proteins to prevent cerebral I/R injury.

2.
Cancer Sci ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32232887

RESUMO

Alternative polyadenylation (APA), which induces shortening of the 3'UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of APA-induced 3'UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3'UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3'UTR could escape from miRNA-mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3'UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/ß-catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knock-down in NPC. Altogether, our results suggested that the 3'UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B-MYH9 -Wnt/ß-catenin axis could represent potential targets for individualized treatment in NPC.

3.
Anal Chim Acta ; 1106: 168-175, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32145845

RESUMO

A ratiometric electrochemical molecular sensing platform for real-time quantification of extracellular hypochlorous acid (HClO) production has been developed based on a latent electrochemical probe aminoferrocene thiocarbamate (AFTC 3). The substrate AFTC consist of a masked redox reporter amino ferrocene (AF 4) linked with a dimethylthiocarbamate trigger via hydroxyl benzyl alcohol. The conceptual idea behind the probe design is based on a specific chemical interaction between HClO and dimethylthiocarbamate, which allows only HClO to unmask the probe to releases AF. The scheme was manipulated to establish a highly selective (in presence of various reactive oxygen species, anions and other biological interfering species) and sensitive (detection limit 75 nM) sensing platform not only in lab samples but also in real samples (food samples, and live cells). Real-time in situ quantification platform was developed to profile HClO productions in macrophages, and it did so with great consistency.

4.
Am J Surg ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32145919

RESUMO

BACKGROUND: The role of surgery in breast cancer liver metastases (BCLM) remains elusive, and current application is limited. Our aim is to investigate whether hepatic resection (HR) of BCLM improves survival compared with non-hepatic resection (NHR) treatment. METHODS: Three hundred and eighty-four patients with BCLM from 2008 to 2018 were divided into two groups. Propensity score matching (PSM) analysis was used to compare the clinical outcomes. RESULTS: After PSM the mean overall survival (OS) and the 1, 3, and 5-year OS rates in HR group were 61.8 months, 92.6%, 54.7% and 54.7%, respectively; while for NHR group these values were 38.6 months, 79.2%, 45.6% and 21.9%, respectively (p < 0.007). Multivariate analysis indicated hormonal receptor status (p = 0.039) and hepatic resection (p = 0.032) were independent prognostic factors. CONCLUSION: Our study revealed that hepatectomy yields a survival benefit safely compared with medical treatments, especially for patients with positive hormonal receptors.

5.
Complement Ther Med ; 49: 102332, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32147062

RESUMO

OBJECTIVES: Much epidemiological evidence links diabetes mellitus (DM) to the development of multiple cancers and, in particular, the development of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether Chinese herbal medicine (CHM) reduces the incidence of HCC in patients receiving Western antidiabetic drugs. INTERVENTIONS AND MAIN OUTCOME MEASURES: This retrospective cohort study used data from the National Health Insurance Research Database involving 81,105 diabetic patients, including 5122 CHM users and 25,966 non-CHM users. Analyses of treatment effects were adjusted for covariates including gender, age, comorbidities, antidiabetic drugs and liver medications. NodeXL software performed a network analysis to identify the 50 most commonly used CHM herbs and formulas. RESULTS: In Cox proportional hazards models adjusted for demographic and clinical characteristics, DM patients exposed to adjuvant CHM therapy were significantly less likely to develop HCC compared with non-CHM users (adjusted hazard ratio [aHR] 0.59; 95 % confidence interval [CI], 0.41-0.87; p = 0.01). Kaplan-Meier analysis revealed a lower 10-year cumulative risk of HCC among CHM users compared with non-CHM users. Amongst the 10 individual CHM herbs and herbal formulas most commonly prescribed for DM, the most frequent were Salvia miltiorrhiza (Dan Shen) and Liu Wei Di Huang Wan, respectively. CONCLUSION: This nationwide retrospective cohort study from Taiwan provides some valuable insights into the prescribing characteristics of CHM treatment in patients with DM. Compared with use of Western antidiabetic medications alone, use of adjuvant CHM effectively reduces the incidence of HCC in patients with DM.

6.
Am J Hosp Palliat Care ; : 1049909120907601, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32116010

RESUMO

BACKGROUND: An increasing number of patients with terminal illnesses prefer to die in their own homes due to aging, high medical payments, a limited number of hospitalization days, and the ability to receive care from family members. However, few studies have been conducted on the subjective perception and value of caregivers for home-based palliative care (HBPC). OBJECTIVE: To identify common themes and topics of primary family caregivers' lived experiences with HBPC when taking care of terminally ill family members. METHODS: We conducted audio-recorded transcripts of one-on-one in-depth interviews of primary family caregivers of HBPC. Through a purposive sampling method, the participants were all interviewed; these interviews were transcribed verbatim and analyzed using a grounded theory approach. RESULTS: A total of 22 primary family caregivers participated in the study. "Wholeheartedly accompanying one's family to the end of life at home" was the core category. Six main themes describing caregivers' experiences emerged from the interviews: (1) learning the basic skills of end-of-life home care, (2) arranging the sharing and rotation of care, (3) preparing for upcoming deaths and funerals, (4) negotiating the cultural and ethical issues of end-of-life home care, (5) ensuring a comfortable life with basic life support, and (6) maintaining care characterized by concern, perseverance, and patience. CONCLUSIONS: Primary family caregivers of HBPC need support and must learn home care skills by means of the holistic approach. It is crucial to establish assessment tools for caregivers' preparedness for HBPC, including biopsychosocial and cultural considerations.

7.
Med Phys ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32153029

RESUMO

PURPOSE: To commission an open source Monte Carlo (MC) dose engine, "MCsquare" for a synchrotron-based proton machine, integrate it into our in-house C++ based I/O user interface and our web-based software platform, expand its functionalities, and improve calculation efficiency for intensity-modulated proton therapy (IMPT). METHODS: We commissioned MCsquare using a double Gaussian beam model based on in-air lateral profiles, integrated depth dose of 97 beam energies, and measurements of various spread-out Bragg peaks (SOBPs). Then we integrated MCsquare into our C++ based dose calculation code and web-based second check platform "DOSeCHECK". We validated the commissioned MCsquare based on twelve different patient geometries and compared the dose calculation with a well-benchmarked GPU-accelerated MC (gMC) dose engine. We further improved the MCsquare efficiency by employing the CT resampling approach. We also expanded its functionality by adding a linear energy transfer (LET)-related model-dependent biological dose calculation. RESULTS: Differences between MCsquare calculations and SOBP measurements were less than 2.5% (less than 1.5% for ~85% of measurements) in water. The dose distributions calculated using MCsquare agreed well with the results calculated using gMC in patient geometries. The average 3D gamma analysis (2%/2mm) passing rates comparing MCsquare and gMC calculations in the twelve patient geometries were 98.0±1.0%. The computation time to calculate one IMPT plan in patients' geometries using an inexpensive CPU workstation (Intel Xeon E5-2680 2.50GHz) was 2.3±1.8 minutes after the variable resolution technique was adopted. All calculations except for one craniospinal patient were finished within 3.5 minutes. CONCLUSION: MCsquare was successfully commissioned for a synchrotron-based proton beam therapy delivery system and integrated into our web-based second check platform. After adopting CT resampling and implementing LET model-dependent biological dose calculation capabilities, MCsquare will be sufficiently efficient and powerful to achieve Monte Carlo-based and LET-guided robust optimization in IMPT, which will be done in the future studies.

8.
Int J Urol ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32153068

RESUMO

OBJECTIVES: To investigate the effectiveness of Chinese herbal medicine for the treatment of urinary incontinence in patients with chronic obstructive pulmonary disease. METHODS: We carried out a retrospective cohort study using the National Health Insurance Research Database. From a cohort of 1 million records between 1996 and 2013, a total of 202 279 patients with newly onset chronic obstructive pulmonary disease were initially recruited. We matched with propensity score 3967 patients who received Chinese herbal medicine by age, sex, year of chronic obstructive pulmonary disease diagnosis, urbanization, comorbidities and chronic obstructive pulmonary disease medications. All participants received follow-up visits until the end of 2013 to record the incidence rate of urinary incontinence. The Cox proportional hazards model was applied to assess the association between Chinese herbal medicine use and the risk of urinary incontinence among chronic obstructive pulmonary disease patients. RESULTS: The incidence rates of urinary incontinence were 57.33 and 108.15 (per 10 000 person-years) in the Chinese herbal medicine and non-Chinese herbal medicine cohorts, respectively, showing a significantly lower risk of urinary incontinence in Chinese herbal medicine users (aHR = 0.56, 95% CI = 0.45-0.69, P < 0.001). The Chinese herbal medicine prescription pattern analysis showed that Fritillariae thunbergii bulbus (Zhebeimu), Semen armeniacae amarum (Kuxingren), Platycodonis radix (Jiegeng), Xiao Qing Long Tang and Ding Chuan Tang constituted the core of Chinese herbal medicine prescriptions applied to treat chronic obstructive pulmonary disease. CONCLUSION: The use of Chinese herbal medicine in chronic obstructive pulmonary disease patients can reduce their risk of urinary incontinence.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32191881

RESUMO

In real-world recognition/classification tasks, limited by various objective factors, it is usually difficult to collect training samples to exhaust all classes when training a recognizer or classifier. A more realistic scenario is open set recognition (OSR), where incomplete knowledge of the world exists at training time, and unknown classes can be submitted to an algorithm during testing, requiring the classifiers to not only accurately classify the seen classes, but also effectively deal with unseen ones. This paper provides a comprehensive survey of existing open set recognition techniques covering various aspects ranging from related definitions, representations of models, datasets, evaluation criteria, and algorithm comparisons. Furthermore, we briefly analyze the relationships between OSR and its related tasks including zero-shot, one-shot (few-shot) recognition/learning techniques, classification with reject option, and so forth. Additionally, we also review the open world recognition which can be seen as a natural extension of OSR. Importantly, we highlight the limitations of existing approaches and point out some promising subsequent research directions in this field.

10.
Jpn J Radiol ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193792

RESUMO

PURPOSE: To determine the association of epicardial adipose tissue (EAT) volume and density with cardiac geometry and function. METHODS: We included 178 consecutive patients who performed coronary computed tomography angiography but were not diagnosed with coronary artery disease (CAD). The EAT volume, density, and following cardiac structure and function parameters were measured: left ventricular ejection fraction, left ventricular mass (LVM), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular stroke volume (LVSV), left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVST) and posterior wall thickness (PWT). All the parameters were standardized using the height2.7. RESULTS: A significant correlation was found between larger EAT volume and increased LVM, LVEDV, LVESV, LVSV, LVEDD, IVST and corresponding standardized indexes (P < 0.05 for all). Higher EAT density significantly correlated with increased LVM, LVEDV, LVESV, LVSV, LVEDD, IVST, PWT and corresponding standardized indexes (P < 0.05 for all). The largest cardiac structure and function parameters were observed in the population with above-median EAT volume and density. CONCLUSION: Both large EAT volume and high EAT density were associated with cardiac structure and function in patients with no CAD. The EAT density may render complementary information to EAT volume regarding cardiac geometry changes.

11.
Curr Biol ; 30(6): 1077-1091.e5, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32142702

RESUMO

Sleep is universal across species and essential for quality of life and health, as evidenced by the consequences of sleep loss. Sleep might homeostatically normalize synaptic gains made over wake states in order to reset information processing and storage and support learning, and sleep-associated synaptic (ultra)structural changes have been demonstrated recently. However, causal relationships between the molecular and (ultra)structural status of synapses, sleep homeostatic regulation, and learning processes have yet to be established. We show here that the status of the presynaptic active zone can directly control sleep in Drosophila. Short sleep mutants showed a brain-wide upregulation of core presynaptic scaffold proteins and release factors. Increasing the gene copy number of ELKS-family scaffold master organizer Bruchpilot (BRP) not only mimicked changes in the active zone scaffold and release proteins but importantly provoked sleep in a dosage-dependent manner, qualitatively and quantitatively reminiscent of sleep deprivation effects. Conversely, reducing the brp copy number decreased sleep in short sleep mutant backgrounds, suggesting a specific role of the active zone plasticity in homeostatic sleep regulation. Finally, elimination of BRP specifically in the sleep-promoting R2 neurons of 4xBRP animals partially restored sleep patterns and rescued learning deficits. Our results suggest that the presynaptic active zone plasticity driven by BRP operates as a sleep homeostatic actuator that also restricts periods of effective learning.

12.
J Chin Med Assoc ; 83(4): 386-393, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32132384

RESUMO

BACKGROUND: The influenza virus is a highly infectious disease, with a notably rapid transmission rate. Autophagy is triggered by viral infection and is a survival mechanism exerted to maintain cellular homeostasis. Catechin is a representative phenolic acid which exerts anti-inflammatory responses against influenza A virus infection. The aim of this study is to explore the anti-H1N1 influenza virus effects by catechin associated with the restoration of autophagy. METHODS: XTT assay was used to detect cellular viability. The inhibitory effects on the H1N1 influenza virus were assessed by hemagglutination assay, neuraminidase activity, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The protein levels of H1N1 influenza virulence and autophagic markers were detected by Western blot. RESULTS: We herein demonstrated that catechin had no cytotoxic effect on both infected and noninfected A549 cells and exerted protective effects on infected A549 cells. The results of the hemagglutination assay, neuraminidase activity, and qRT-PCR to examine viral load demonstrated that catechin effectively inhibited the replication of the H1N1 influenza virus. The virulent M2 protein and viral nucleoprotein were also inhibited after treatment with catechin. As for the autophagic markers, the LC3B protein was notably decreased by catechin in a dose-dependent manner, while the amount of autophagic vacuoles in H1N1 influenza virus-infected cells also decreased after catechin treatment in a dose-dependent manner. CONCLUSION: Collectively, the autophagy activated by the H1N1 influenza virus could be reversed after catechin treatment. This study indicates that catechin effectively inhibits H1N1 viral proliferation and thus may be applied as an adjuvant in future clinical application.

13.
Food Chem Toxicol ; 139: 111274, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32198028

RESUMO

Fumonisin B1 (FB1) is a mycotoxin that contaminates cash crops and has toxic effects on humans and livestock. However, the toxic effect of FB1 is not fully understood. In this study, the apoptosis mechanism of FB1 on porcine kidney cells (PK-15) was elucidated by transcriptome analysis. The results showed that FB1 observably changed the expression of mRNA in PK-15 and induced the cells of apoptosis after being exposed to 106 µM FB1 in vitro. Gene Ontology and KEGG enrichment analyses showed that FB1 exposure increased the expressions of related mRNA in TNF signalling pathway in PK-15. To verify our bioinformatics analysis, these changes were verified by qRT-PCR and Western blot assay. Furthermore, the mRNA expressions of NF-κB and its downstream genes or proteins decreased significantly (p < 0.01) after the addition of BAY11-7082, the inhibitor of NF-κB. Therefore, for the first time, we demonstrate that FB1 can induce apoptosis of PK-15 cells through TNF signalling pathway, and NF-κB gene is a target of FB1 acting on the TNF signalling pathway.

14.
J Neurosci ; 40(14): 2817-2827, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122953

RESUMO

Perturbations to postsynaptic glutamate receptors (GluRs) trigger retrograde signaling to precisely increase presynaptic neurotransmitter release, maintaining stable levels of synaptic strength, a process referred to as homeostatic regulation. However, the structural change of homeostatic regulation remains poorly defined. At wild-type Drosophila neuromuscular junction synapse, there is one Bruchpilot (Brp) ring detected by superresolution microscopy at active zones (AZs). In the present study, we report multiple Brp rings (i.e., multiple T-bars seen by electron microscopy) at AZs of both male and female larvae when GluRs are reduced. At GluRIIC-deficient neuromuscular junctions, quantal size was reduced but quantal content was increased, indicative of homeostatic presynaptic potentiation. Consistently, multiple Brp rings at AZs were observed in the two classic synaptic homeostasis models (i.e., GluRIIA mutant and pharmacological blockade of GluRIIA activity). Furthermore, postsynaptic overexpression of the cell adhesion protein Neuroligin 1 partially rescued multiple Brp rings phenotype. Our study thus supports that the formation of multiple Brp rings at AZs might be a structural basis for synaptic homeostasis.SIGNIFICANCE STATEMENT Synaptic homeostasis is a conserved fundamental mechanism to maintain efficient neurotransmission of neural networks. Active zones (AZs) are characterized by an electron-dense cytomatrix, which is largely composed of Bruchpilot (Brp) at the Drosophila neuromuscular junction synapses. It is not clear how the structure of AZs changes during homeostatic regulation. To address this question, we examined the structure of AZs by superresolution microscopy and electron microscopy during homeostatic regulation. Our results reveal multiple Brp rings at AZs of glutamate receptor-deficient neuromuscular junction synapses compared with single Brp ring at AZs in wild type (WT). We further show that Neuroligin 1-mediated retrograde signaling regulates multiple Brp ring formation at glutamate receptor-deficient synapses. This study thus reveals a regulatory mechanism for synaptic homeostasis.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32117815

RESUMO

Bacterial infection remains one of the leading causes of death worldwide due to the continuous rise of multiple antibiotic-resistant bacteria. Focusing solely on bacteria as the drug targets is a major limitation inherent in the conventional antibiotic therapy. Recently, host-directed therapies have become such an innovative approach to modulate the host defense system and the interplay of innate and adaptive immunity. Our previous studies showed that memantine (MEM), an α7 nAChR antagonist, could efficiently block multi-drug resistant Escherichia coli-caused bacteremia and meningitis in a mouse model. However, the underlying mechanisms that govern the antibacterial effects of MEM are still unknown. In this study, we demonstrated that MEM is able to significantly suppress E. coli infection by enhancing E. coli-induced formation and release of NETs in vitro and in vivo. MEM could promote the trapping and bactericidal activities of the polymorphonuclear neutrophils (PMNs) in a manner dependent on α7 nAChR, since knockdown of this receptor noticeably reduces the survival ability of bacteria in PMNs while MEM no longer affects the survival of bacteria in PMNs. Our results also showed that when the expression of S100A9, an antiseptic protein, is inhibited, pathogen survival rates in PMNs increase significantly. MEM reverses this effect in a concentration-dependent manner. MEM stimulates the production of MPO, S100A9, and DNA in PMNs and accelerates the release of depolymerized chromatin fibers into the extracellular space, suggesting the formation of NETs. Taken together, our data suggest that MEM effectively blocks bacterial infection through the promotion of the antibacterial function of NETs induced by E. coli.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32050043

RESUMO

Vibralactone is isolated from the basidiomycete fungus Boreostereum vibrans as one of the strongest lipase inhibitors. Its unusual ß-lactone-fused bicycle is derived from an aryl ring moiety by an oxidative ring-expansion prior to an intramolecular cyclization. Herein, we report the discovery of the cyclase VibC which belongs to the α/ß-hydrolase superfamily and is involved in the vibralactone biosynthesis. Biochemical and crystal studies suggest that VibC may catalyze an aldol or an electrocyclic reaction initiated by the Ser-His-Asp catalytic triad. For the aldol and pericyclic chemistry in living cells, VibC is a unique hydrolase performing the carbocycle formation of an oxepinone to a fused bicyclic ß-lactone. This presents a naturally occurring, new enzymatic reaction in both aldol and hydrolase (bio)chemistry that will guide future exploitation of these enzymes in synthetic biology for chemical-diversity expansion of natural products.

17.
Ci Ji Yi Xue Za Zhi ; 32(1): 75-81, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110525

RESUMO

Objectives: The objective of the study is to report the acute and late toxicity and preliminary results of localized prostate cancer treated with high-dose radiation therapy (RT). Materials and Methods: Between March 2010 and October 2018, a total of 53 patients with clinically localized prostate cancer were treated with definitive RT at our institution. All patients were planned to receive a total dose of 81 Gy with the volumetric-modulated arc therapy technique. Patients were stratified by prognostic risk groups based on the National Comprehensive Cancer Network risk classification criteria. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. The definition of biochemical failure was using the 2005 ASTRO Phoenix consensus definition. Median follow-up time was 46.5 months (range: 4.7-81.0 months). Results: The 3-year biochemical failure-free survival rates for low-, intermediate-, and high-risk group patients were 100%, 87.5%, and 84%, respectively. The 3- and 5-year overall survival rates were 83% and 62%, respectively. Three (5.6%) patients developed Grade II acute gastrointestinal (GI) toxicity. Four (7.5%) patients developed Grade II acute genitourinary (GU) toxicity, and none experienced Grade III or higher acute GI or GU symptoms. One (1.8%) patient developed Grade II or higher late GI toxicity. Six (11.3%) patients experienced Grade II late GU toxicity. No Grade III or higher late GI and GU complications have been observed. Conclusions: Data from the current study demonstrated the feasibility of dose escalation with image-guided and volumetric-modulated arc therapy techniques for the treatment of localized prostate cancer. Minimal acute and late toxicities were observed from patients in this study. Long-term prostate-specific antigen controls are comparable to previously published results of high-dose intensity-modulated RT for localized prostate cancer. Based on this favorable outcome, dose escalation (81 Gy) has become the standard treatment for localized prostate cancer at our institution.

18.
Inorg Chem ; 59(6): 4096-4108, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32105456

RESUMO

To evaluate the effect of ligand geometry on the coordination number, number of inner-sphere water molecules, and affinity for anions of the corresponding lanthanide complex, six tris-bidentate 1,2-hydroxypyridonate (HOPO) europium(III) complexes with different cap sizes were synthesized and characterized. Wider or more flexible ligand caps, such as in EuIII-TREN-Gly-HOPO and EuIII-3,3-Gly-HOPO, enable the formation of nine-coordinate europium(III) complexes bearing three inner-sphere water molecules. In contrast, smaller or more rigid caps, such as in EuIII-TREN-HOPO, EuIII-2,2-Li-HOPO, EuIII-3,3-Li-HOPO, and EuIII-2,2-Gly-HOPO, favor eight-coordinate europium(III) complexes that have only two inner-sphere water molecules. Notably, there is no correlation between the number of inner-sphere water molecules and the affinity of the Eu(III) complexes for phosphate. Some q = 2 (EuIII-TREN-HOPO, EuIII-3,3-Li-HOPO, and EuIII-2,2-Gly-HOPO) and some q = 3 (EuIII-TREN-Gly-HOPO) complexes have no affinity for anions, whereas one q = 2 complex (EuIII-2,2-Li-HOPO) and one q = 3 complex (EuIII-3,3-Gly-HOPO) have a high affinity for phosphate. For the latter two systems, each inner-sphere water molecule is replaced with a phosphate anion, resulting in the formation of EuLPi2 and EuLPi3 adducts, respectively.

19.
Lab Chip ; 20(6): 1103-1109, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32040102

RESUMO

Accurate cancer diagnostic methods are of urgent need. Since traditional immunohistochemistry (IHC)-based approaches, while reliable, are labor-intensive and require well-trained technicians, we developed an integrated microfluidic platform capable of labeling ovarian cancer biomarkers (i.e. aptamer) within formalin-fixed, paraffin embedded tissues via molecular probes. Both aptamer-based 1) fluorescent staining and 2) IHC staining of clinical tissue samples could be automated in the microfluidic system in only 2-3 h (40-50% faster than conventional approaches) with <0.5 mL of reagents, signifying that this device could serve as a promising diagnostic tool for ovarian cancer.

20.
Respir Care ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071134

RESUMO

BACKGROUND: Soft mist inhalers (SMIs) generate aerosols with a smaller particle size than pressurized metered-dose inhalers (pMDIs). However, the whole-span particle size distribution (PSD) of SMIs and the optimal delivery method of SMIs during mechanical ventilation have not been fully investigated. This study aimed to measure the PSD of the SMI alone and the SMI coupled to an inhalation aid (eg, a spacer, a valved holding chamber), as well as the delivery efficiency of SMI in different actuation timings and circuit positions during mechanical ventilation. As a suitable comparison, the pMDI was chosen for the same measurement. METHODS: SMIs (2.5 µg/actuation of tiotropium) were compared with pMDIs (100 µg/actuation of salbutamol). A microorifice uniform deposit impactor was utilized for the particle sizing of drug aerosols generated by inhalers alone, inhalers with a spacer, and inhalers with a valved holding chamber. To optimize the delivery efficiency of both inhalers during mechanical ventilation, the operating parameters included the circuit positions and actuation timings in the ventilator circuit. Particle sizes and inhaled doses were measured with an optical particle sizer and filters used to collect and quantify the drug, respectively. RESULTS: The SMI generated a smaller mass medium aerodynamic diameter (MMAD) than that from the pMDI. The extrafine-particle fraction (EFPF, < 1 µm) of the SMI was significantly higher than that of the pMDI. With the use of either inhalation aid, the MMAD of both inhalers decreased, and both inhalers with inhalation aid showed significant increases in EFPF. During mechanical ventilation, the optimum way to deliver the SMI and pMDI was at 15 cm from the Y-piece and actuated at the end of expiration and the onset of inspiration, respectively. CONCLUSIONS: The SMI with an inhalation aid showed marginal improvement on the PSD. The inhaler type, actuation timing, and position within the circuit also played important roles in delivery efficiency during mechanical ventilation.

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