Label-free quantitative proteomics of CD133-positive liver cancer stem cells

Abstract Background CD133-positive liver cancer stem cells, which are characterized by their resistance to conventional chemotherapy and their tumor initiation ability at limited dilutions, have been recognized as a critical target in liver cancer therapeutics. In the current work, we developed a label-free quantitative method to investigate the proteome of CD133-positive liver cancer stem cells for the purpose of identifying unique biomarkers that can be utilized for targeting liver cancer stem cells. Label-free quantitation was performed in combination with ID-based Elution time Alignment by Linear regression Quantitation (IDEAL-Q) and MaxQuant. Results Initially, IDEAL-Q analysis revealed that 151 proteins were differentially expressed in the CD133-positive hepatoma cells when compared with CD133-negative cells. We then analyzed these 151 differentially expressed proteins by MaxQuant software and identified 10 significantly up-regulated proteins. The results were further validated by RT-PCR, western blot, flow cytometry or immunofluorescent staining which revealed that prominin-1, annexin A1, annexin A3, transgelin, creatine kinase B, vimentin, and EpCAM were indeed highly expressed in the CD133-positive hepatoma cells. Conclusions These findings confirmed that mass spectrometry-based label-free quantitative proteomics can be used to gain insights into liver cancer stem cells.http://deepblue.lib.umich.edu/bitstream/2027.42/113089/1/12953_2012_Article_407.pd

Early drainage reduces the length of hospital stay in patients with lung abscess

BackgroundAlthough percutaneous transthoracic catheter drainage (PCD) has been proven effective in lung abscesses, the optimal timing of PCD is still unclear. The study aimed to evaluate the safety and efficacy of early versus delayed drainage in patients with lung abscesses.MethodsThis retrospective study included 103 consecutive patients with liquefied lung abscesses more than 3 cm confirmed by a CT scan received CT-guided PCD over 16 years, from July 2005 to September 2021, in a single institution were reviewed. Early drainage was defined as PCD within one week after a lung abscess was diagnosed. The primary outcome was 90-day mortality. The secondary outcomes included perioperative complications and patients’ length of hospital stay (LoS). Factors associated with 90-day mortality and LoS were also analyzed. The key statistical methods were Chi-square test, Fisher’s exact test, Student t-test, and Pearson correlation.ResultsAmount the 103 patients, there were 64 patients who received early PCD, and 39 patients received delayed PCD. Between the two groups, there were no significant differences in clinical characteristics, 90-day mortality, or perioperative complications. The LoS was significantly shortened in early PCD group (28.6 ± 25.5 vs. 39.3 ± 26.8 (days), p = 0.045). Higher Charlson comorbidity index, secondary lung abscess, and liver cirrhosis were associated with higher mortality (all p < 0.05). Positive sputum culture significantly increased the LoS (coefficient 19.35 (10.19, 28.50), p < 0.001).ConclusionThe 90-day mortality and complications were similar for early PCD and delayed PCD patients, but LoS was significantly shortened in early PCD patient

Adipose-Derived Mesenchymal Stem Cell Protects Kidneys against Ischemia-Reperfusion Injury through Suppressing Oxidative Stress and Inflammatory Reaction

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species are important mediators exerting toxic effects on various organs during ischemia-reperfusion (IR) injury. We hypothesized that adipose-derived mesenchymal stem cells (ADMSCs) protect the kidney against oxidative stress and inflammatory stimuli in rat during renal IR injury.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus immediate intra-renal administration of 1.0 × 10⁶autologous ADMSCs, followed by intravenous ADMSCs at 6 h and 24 h after IR). The duration of ischemia was 1 h, followed by 72 hours of reperfusion before the animals were sacrificed.</p> <p>Results</p> <p>Serum creatinine and blood urea nitrogen levels and the degree of histological abnormalities were markedly lower in group 3 than in group 2 (all p < 0.03). The mRNA expressions of inflammatory, oxidative stress, and apoptotic biomarkers were lower, whereas the anti-inflammatory, anti-oxidative, and anti-apoptotic biomarkers were higher in group 3 than in group 2 (all p < 0.03). Immunofluorescent staining showed a higher number of CD31+, von Willebrand Factor+, and heme oxygenase (HO)-1+ cells in group 3 than in group 2 (all p < 0.05). Western blot showed notably higher NAD(P)H quinone oxidoreductase 1 and HO-1 activities, two indicators of anti-oxidative capacity, in group 3 than those in group 2 (all p < 0.04). Immunohistochemical staining showed higher glutathione peroxidase and glutathione reductase activities in group 3 than in group 2 (all p < 0.02)</p> <p>Conclusion</p> <p>ADMSC therapy minimized kidney damage after IR injury through suppressing oxidative stress and inflammatory response.</p

Cognitive effects and tolerability of non-invasive brain stimulation on Alzheimer’s disease and mild cognitive impairment: a component network meta-analysis

Objectives: To compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits. Methods: Electronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre–post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and ≥3 months) after brain stimulation was examined. Results: We included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%–11.1%). HFrTMS (1.08, 9, 0.35–1.80) and atDCS (0.56, 0.03–1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (−0.79, –2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77–2.54) and ctDCS (2.57, 0.20–4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated.\ud Conclusions: HFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI

Characteristics of predictor sets found using differential prioritization

<p>Abstract</p> <p>Background</p> <p>Feature selection plays an undeniably important role in classification problems involving high dimensional datasets such as microarray datasets. For filter-based feature selection, two well-known criteria used in forming predictor sets are relevance and redundancy. However, there is a third criterion which is at least as important as the other two in affecting the efficacy of the resulting predictor sets. This criterion is the degree of differential prioritization (DDP), which varies the emphases on relevance and redundancy depending on the value of the DDP. Previous empirical works on publicly available microarray datasets have confirmed the effectiveness of the DDP in molecular classification. We now propose to establish the fundamental strengths and merits of the DDP-based feature selection technique. This is to be done through a simulation study which involves vigorous analyses of the characteristics of predictor sets found using different values of the DDP from toy datasets designed to mimic real-life microarray datasets.</p> <p>Results</p> <p>A simulation study employing analytical measures such as the distance between classes before and after transformation using principal component analysis is implemented on toy datasets. From these analyses, the necessity of adjusting the differential prioritization based on the dataset of interest is established. This conclusion is supported by comparisons against both simplistic rank-based selection and state-of-the-art equal-priorities scoring methods, which demonstrates the superiority of the DDP-based feature selection technique. Reapplying similar analyses to real-life multiclass microarray datasets provides further confirmation of our findings and of the significance of the DDP for practical applications.</p> <p>Conclusion</p> <p>The findings have been achieved based on analytical evaluations, not empirical evaluation involving classifiers, thus providing further basis for the usefulness of the DDP and validating the need for unequal priorities on relevance and redundancy during feature selection for microarray datasets, especially highly multiclass datasets.</p

Mortality rates in Alzheimer's disease and non-Alzheimer's dementias: a systematic review and meta-analysis

Background People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia might aid in the development of preventive interventions for the most vulnerable populations. The aim of this study was to compare the difference in mortality rates between individuals without dementia and individuals with various types of dementia. Methods For this systematic review and meta-analysis, we did a systematic search of MEDLINE, PubMed, Embase, and Cochrane Library from inception to July 11, 2020, for cross-sectional or cohort studies that assessed mortality and survival-related outcomes among people with different types of dementia compared with people without dementia. Single-arm studies without comparison groups and autopsy studies or family studies that used a selected sample were excluded. The Newcastle-Ottawa Scale was used by two authors (D-JL and C-SC) independently to measure the methodological quality of included studies, and two authors (F-CY and P-TT) independently extracted data. We assessed differences in all-cause mortality rate and survival time from dementia diagnosis between individuals without dementia, individuals with Alzheimer's disease, and individuals with non-Alzheimer's disease dementias. The secondary outcomes were age at death and survival time from disease onset. Random-effects meta-analyses were done. Effect sizes included hazard ratios (HRs) and mean differences (MDs) with 95% CIs. Potential moderators, including age-associated moderators, were identified through meta-regression and subgroup analyses. This study is registered with PROSPERO, CRD42020198786. Findings Our database search identified 11 973 records, and we included 78 eligible studies in our analyses, encompassing 63 125 individuals with dementia and 152 353 controls. Individuals with any type of dementia had a higher mortality rate than individuals without dementia (HR 5·90, 95% CI 3·53 to 9·86), and the HR for all-cause mortality was highest for Lewy body dementia (17·88, 5·87 to 54·46). After diagnosis, the mean survival time for people with Alzheimer's disease was 5·8 years (SD 2·0). Compared with people with Alzheimer's disease, a diagnosis of any non-Alzheimer's disease dementia was associated with a higher risk of all-cause mortality (HR 1·33, 1·21 to 1·46), a shorter survival time from diagnosis (MD −1·12 years, 95% CI −1·52 to −0·72), and a younger age at death (−1·76 years, −2·66 to −0·85). Survival time from disease onset was also shorter in people with non-Alzheimer's dementia, across types, compared with people with Alzheimer's disease, but the subgroup analysis revealed that this difference was only significant for vascular dementia (MD −1·27 years, −1·90 to −0·65) and dementia with Lewy bodies (MD −1·06 years, −1·68 to −0·44). The interactions between age and several survival-related outcomes were significant. 39 (50%) of the 78 included studies were rated as good quality, and large heterogeneity (I2>75%) was observed for most of the study outcomes. Interpretation Alzheimer's disease is the most common type of dementia and one of the major causes of mortality worldwide. However, the findings from the current study suggest that non-Alzheimer's disease dementias were associated with higher morality rates and shorter life expectancy than Alzheimer's disease. Developing tailored treatment and rehabilitation programmes for different types of dementia is important for mental health providers, patients, and their families

Direct Semi-Synthesis of the Anticancer Lead-Drug Protoapigenone from Apigenin, and Synthesis of Further New Cytotoxic Protoflavone Derivatives

Protoapigenone, a natural flavonoid possessing an unusual p-quinol moiety on its B-ring, is a novel prospective anticancer agent with low toxicity that is currently in development. The first economical, one-step synthesis of protoapigenone from apigenin is described on up to gram scale. 13 new 1′-O-alkylflavone analogs were also synthesized, either from apigenin or β-naphthoflavone. The in vitro cytotoxic activity of each compound was tested on six human cancer cell lines (HepG2, Hep3B, Ca9-22, A549, MCF-7 and MDA-MB-231). In the case of 1′-O-alkyl-protoapigenone derivatives, structure-activity relationships were found depending on the side-chain, and protoapigenone 1′-O-butyl ether was found to exert significantly stronger activity against three of the cell lines (Hep3B, MCF-7 and MDA-MB-231) than its non-substituted analog, protoapigenone itself. In contrast to this, all β-naphthoflavone derivatives bearing the same pharmacophore on their B-ring showed decreased cytotoxic activities when substituted with an O-alkyl side-chain at position 1′, comparing to that of the non-substituted compound

Pulmonary Tuberculosis and Delay in Anti-Tuberculous Treatment Are Important Risk Factors for Chronic Obstructive Pulmonary Disease

OBJECTIVE: Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database. MAIN OUTCOME MEASURES: Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment. RESULTS: The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768-2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD. CONCLUSIONS: Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients