All-Trans Retinoic Acid Induces DU145 Cell Cycle Arrest through Cdk5 Activation

All-trans retinoic acid (ATRA), the active form of vitamin A, plays an important role in the growth arrest of numerous types of cancer cells. It has been indicated that cyclin-dependent kinase 5 (Cdk5) activity can be affected by ATRA treatment. Our previous results demonstrate the involvement of Cdk5 in the fate of prostate cancer cells. The purpose of this study is to examine whether Cdk5 is involved in ATRA-induced growth arrest of the castration-resistant cancer cell line DU145 through up-regulating Cdk inhibitor protein, p27

Supramolecular Aptamers on Graphene Oxide for Efficient Inhibition of Thrombin Activity

Graphene oxide (GO), a two-dimensional material with a high aspect ratio and polar functional groups, can physically adsorb single-strand DNA through different types of interactions, such as hydrogen bonding and π-π stacking, making it an attractive nanocarrier for nucleic acids. In this work, we demonstrate a strategy to target exosites I and II of thrombin simultaneously by using programmed hybrid-aptamers for enhanced anticoagulation efficiency and stability. The targeting ligand is denoted as Supra-TBA15/29 (supramolecular TBA15/29), containing TBA15 (a 15-base nucleotide, targeting exosite I of thrombin) and TBA29 (a 29-base nucleotide, targeting exosite II of thrombin), and it is designed to allow consecutive hybridization of TBA15 and TBA29 to form a network of TBAs (i.e., supra-TBA15/29). The programmed hybrid-aptamers (Supra-TBA15/29) were self-assembled on GO to further boost anticoagulation activity by inhibiting thrombin activity, and thus suppress the thrombin-induced fibrin formation from fibrinogen. The Supra-TBA15/29-GO composite was formed mainly through multivalent interaction between poly(adenine) from Supra-TBA15/29 and GO. We controlled the assembly of Supra-TBA15/29 on GO by regulating the preparation temperature and the concentration ratio of Supra-TBA15/29 to GO to optimize the distance between TBA15 and TBA29 units, aptamer density, and aptamer orientation on the GO surfaces. The dose-dependent thrombin clotting time (TCT) delay caused by Supra-TBA15/29-GO was >10 times longer than that of common anticoagulant drugs including heparin, argatroban, hirudin, and warfarin. Supra-TBA15/29-GO exhibits high biocompatibility, which has been proved by in vitro cytotoxicity and hemolysis assays. In addition, the thromboelastography of whole-blood coagulation and rat-tail bleeding assays indicate the anticoagulation ability of Supra-TBA15/29-GO is superior to the most widely used anticoagulant (heparin). Our highly biocompatible Supra-TBA15/29-GO with strong multivalent interaction with thrombin [dissociation constant (Kd) = 1.9 × 10−11 M] shows great potential as an effective direct thrombin inhibitor for the treatment of hemostatic disorders

Chinese Herbal Medicine Improves the Long-Term Survival Rate of Patients With Chronic Kidney Disease in Taiwan: A Nationwide Retrospective Population-Based Cohort Study

Background and purpose: Chinese herbal medicine (CHM) is frequently applied in conjunction with western pharmacotherapy to relieve symptoms in patients with CKD. However, evidence-based research into the effectiveness of CHM use as applied to treat CKD is limited and warrants further investigation. The aim of this study is to assess whether adjunctive treatment with CHM affected survival rate of CKD patients undergoing conventional western medical management.Methods: A total of 14,718 CKD patients, including 6,958 CHM users and 7,760 non-CHM users, were recruited from the Longitudinal Health Insurance Database 2000, a sub-dataset of the National Health Insurance Research Database, to conduct this study. Demographic characteristics, including sex, age, job type, residential area, and comorbidity were considered as covariates to adjust the analysis. A network analysis of treatments, including with herbal formulas and single herbs, was performed to investigate the core patterns of CHM use for the treatment of CKD patients. The Kaplan-Meier method was used to determine the survival rate between CHM and non-CHM groups.Results: After matching for sex and age, there were 550 subjects in both the CHM and non-CHM cohorts. Other than presence of diabetes (adjusted OR = 0.57, p < 0.001) and urinary tract infection (adjusted OR = 0.69, p < 0.05), sex, age, job type, area of residence, and other comorbidities indicated no special preference for CHM use among subjects. Salvia miltiorrhiza Bunge (SM) and Ji-Sheng-Shen-Qi-Wan (JSSQW) were the most frequent single herb and formula, respectively, prescribed for patients with CKD. The most frequent CHM combination between herbs and formulas was JSSQW, associated with Rheum officinale Baill. (RO), SM and Astragalus membranaceus (Fisch.) Bunge (AM). The long-term survival rate demonstrated significant benefits for CHM users within a 12-year follow-up period (P < 0.004).Conclusion: This nationwide retrospective cohort study provides valuable insight into the characteristics and prescription patterns of CHM usage in CKD patients. JSSQW associated with RO, SM, and AM is the most common CHM prescription. CHM improves long-term survival in patients with CKD, suggesting that CHM is an effective adjuvant therapy for CKD

Which digit is larger? Brain responses to number and size interactions in a numerical Stroop task

When comparing the digits of different physical sizes, the processing of numerical value interacts with the processing of physical size. Given the universal use of Arabic numbers in mathematics and daily life, this study aims to elucidate the cognitive processes involved in the interactions of task-relevant and task-irrelevant features during information processing. We investigated this question by examining event-related potential (ERP) using a modified version of the size congruity comparison, which is a Stroop-like task. Numerical value and physical size were varied independently under task-relevant and task-irrelevant conditions. To better examine how the task-irrelevant features modulated the processing of the task-relevant attributes, a neutral condition was included in both tasks. For the physical task, congruent trials showed a less negative N200 response than neutral trials (indicating a facilitation effect), and incongruent trials elicited a larger N450 and smaller late positive complex (LPC) response than neutral trials (indicating an interference effect). For the numerical task, congruent trials showed a larger LPC response than neutral trials (indicating a facilitation effect). These ERP findings indicate that the sources of the facilitation and interference effects appear in different cognitive processes for each task. We further suggest that language characteristics may be a factor in the superior numerical processing exhibited in this study

Chinese Herbal Medicine as an Adjunctive Therapy Ameliorated the Incidence of Chronic Hepatitis in Patients with Breast Cancer: A Nationwide Population-Based Cohort Study

We conducted a National Health Insurance Research Database-based Taiwanese nationwide population-based cohort study to evaluate whether Chinese herbal medicine (CHM) treatment decreased the incidence of chronic hepatitis in breast cancer patients receiving chemotherapy and/or radiotherapy. A total of 81171 patients were diagnosed with breast cancer within the defined study period. After randomly equal matching, data from 13856 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence and therapeutic potential of CHM in patients with breast cancer. The patients with breast cancer receiving CHM treatment exhibited a significantly decreased incidence rate of chronic hepatitis even across the stratification of age, CCI score, and treatments. The cumulative incidence of chronic hepatitis for a period of seven years after initial breast cancer diagnosis was also reduced in the patients receiving CHM treatment. The ten most commonly used single herbs and formulas were effective in protecting liver function in patients with breast cancer, where Hedyotis diffusa and Jia-Wei-Xiao-Yao-San were the most commonly used herbal agents. In conclusion, our study provided information that western medicine therapy combined with CHM as an adjuvant modality may have a significant impact on liver protection in patients with breast cancer

Mortality risk factors in patients with Acinetobacter baumannii ventilator-associated pneumonia

Background/PurposeVentilator-associated pneumonia (VAP) caused by Acinetobacter baumannii has contributed to high mortality rate, prolonged stays in the intensive care unit, and the rapid development of antimicrobial resistance to commonly used antimicrobials. This study sought to determine predictors of mortality and carbapenem resistance for patients with A baumannii VAP.MethodsWe retrospectively reviewed 541 adult patients with A baumannii pneumonia, who were admitted to a medical center between 2005 and 2007; of which 180 (33.3%) had been treated with mechanical ventilation. Of the 180 patients, 98 (54.4%) who survived were categorized as the survivor group, and 82 (45.6%) who died as the mortality group. Eighty-seven (48.3%) with imipenem-sensitive A baumannii VAP were categorized as the IS-AB group, and the remaining 93 (51.7%) with imipenem-resistant VAP as the IR-AB group.ResultsCompared with the survivor group, the mortality group had significantly higher Charlson comorbidity index scores, and more neoplastic disease, other sites of infection, bloodstream infections, altered mental status, confusion, urea >7 mmol/L, respiratory rate >30/min, low blood pressure (systolic <90 mmHg or diastolic <60 mmHg), age >65 years (CURB-65) ≥ 3, creatinine > 1.6 mg/dL, C-reactive protein ≥ 100 mg/L, and imipenem resistance. The survivor group had more cases of tracheostomy and diabetes mellitus than the mortality group had. Compared with the IS-AB group, the IR-AB group had higher Charlson comorbidity index scores, longer stays before VAP onset, an increase in other sites of infection, white blood cell count <4/μL or >1.1 × 104/μL, and higher hospital mortality rates.ConclusionInadequate initial empiric antimicrobial therapy and higher disease severity scores, including CURB ≥ 3 and C-reactive protein ≥ 120 mg/L, were independent risk factors associated with higher mortality rates for A baumannii pneumonia. Length of stay before VAP and white blood cell count <4/μL or >1.1 × 104/μL were independent risk factors for carbapenem resistance

Microfluidic assisted synthesis of silver nanoparticle–chitosan composite microparticles for antibacterial applications

AbstractSilver nanoparticle (Ag NP)-loaded chitosan composites have numerous biomedical applications; however, fabricating uniform composite microparticles remains challenging. This paper presents a novel microfluidic approach for single-step and in situ synthesis of Ag NP-loaded chitosan microparticles. This proposed approach enables obtaining uniform and monodisperse Ag NP-loaded chitosan microparticles measuring several hundred micrometers. In addition, the diameter of the composites can be tuned by adjusting the flow on the microfluidic chip. The composite particles containing Ag NPs were characterized using UV–vis spectra and scanning electron microscopy-energy dispersive X-ray spectrometry data. The characteristic peaks of Ag NPs in the UV–vis spectra and the element mapping or pattern revealed the formation of nanosized silver particles. The results of antibacterial tests indicated that both chitosan and composite particles showed antibacterial ability, and Ag NPs could enhance the inhibition rate and exhibited dose-dependent antibacterial ability. Because of the properties of Ag NPs and chitosan, the synthesized composite microparticles can be used in several future potential applications, such as bactericidal agents for water disinfection, antipathogens, and surface plasma resonance enhancers

Committed Private Information Retrieval

A private information retrieval (PIR) scheme allows a client to retrieve a data item $x_i$ among $n$ items $x_1,x_2,\ldots,x_n$ from $k$ servers, without revealing what $i$ is even when $t < k$ servers collude and try to learn $i$. Such a PIR scheme is said to be $t$-private. A PIR scheme is $v$-verifiable if the client can verify the correctness of the retrieved $x_i$ even when $v \leq k$ servers collude and try to fool the client by sending manipulated data. Most of the previous works in the literature on PIR assumed that $v < k$, leaving the case of all-colluding servers open. We propose a generic construction that combines a linear map commitment (LMC) and an arbitrary linear PIR scheme to produce a $k$-verifiable PIR scheme, termed a committed PIR scheme. Such a scheme guarantees that even in the worst scenario, when all servers are under the control of an attacker, although the privacy is unavoidably lost, the client won't be fooled into accepting an incorrect $x_i$. We demonstrate the practicality of our proposal by implementing the committed PIR schemes based on the Lai-Malavolta LMC and three well-known PIR schemes using the GMP library and blst, the current fastest C library for elliptic curve pairings.Comment: Accepted at ESORICS 202