Interleukin (IL)-8 plays a vital role in regulating inflammation and breast cancer formation by activating CXCR1/2. We previously designed an antagonist peptide, (RF16), to inhibits the activation of ...downstream signaling pathways by competing with IL-8 in binding to CXCR1/2, thereby inhibiting IL-8-induced chemoattractant monocyte binding. To evaluate the effect of the RF16 peptide on breast cancer progression, triple-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells were used to investigate whether RF16 can inhibit the IL-8-induced breast cancer metastasis. Using growth, proliferation, and invasiveness assays, the results revealed that RF16 reduced cell proliferation, migration, and invasiveness in MDA-MB-231 cells. The RF16 peptide also regulated the protein and mRNA expressions of epithelial–mesenchymal transition (EMT) markers in IL-8-stimulated MDA-MB-231 cells. It also inhibited downstream IL-8 signaling and the IL-8-induced inflammatory response via the mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) pathways. In the xenograft tumor mouse model, RF16 synergistically reinforces the antitumor efficacy of docetaxel by improving mouse survival and retarding tumor growth. Our results indicate that RF16 significantly inhibited IL-8-stimulated cell growth, migration, and invasion in MDA-MB-231 breast cancer cells by blocking the activation of p38 and AKT cascades. It indicated that the RF16 peptide may serve as a new supplementary drug for breast cancer.
Since the advent of modern science, researchers have had to rely on their technical skills or the support of specialized workshops to construct analytical instruments. The notion of the 'fourth ...industrial revolution' promotes construction of customized systems by individuals using widely available, inexpensive electronic modules. This protocol shows how chemists and biochemists can utilize a broad range of microcontroller boards (MCBs) and single-board computers (SBCs) to improve experimental designs and address scientific questions. We provide seven example procedures for laboratory routines that can be expedited by implementing this technology: (i) injection of microliter-volume liquid plugs into microscale capillaries for low-volume assays; (ii) transfer of liquid extract to a mass spectrometer; (iii) liquid-gas extraction of volatile organic compounds (called 'fizzy extraction'), followed by mass spectrometric detection; (iv) monitoring of experimental conditions over the Internet cloud in real time; (v) transfer of analytes to a mass spectrometer via a liquid microjunction interface, data acquisition, and data deposition into the Internet cloud; (vi) feedback control of a biochemical reaction; and (vii) optimization of sample flow rate in direct-infusion mass spectrometry. The protocol constitutes a primer for chemists and biochemists who would like to take advantage of MCBs and SBCs in daily experimentation. It is assumed that the readers have not attended any courses related to electronics or programming. Using the instructions provided in this protocol and the cited material, readers should be able to assemble simple systems to facilitate various procedures performed in chemical and biochemical laboratories in 1-2 d.
Complete disease journey and risk factors for poor outcomes are needed to facilitate effectiveness evaluations of new therapies and clinical decision-making in B-cell Non-Hodgkin lymphoma (B-NHL), ...particularly in Asia where such data are lacking. This retrospective cohort study used electronic medical records from a regional medical centre in southern Taiwan to follow-up 441 patients newly diagnosed with common B-NHL subtypes: Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone Lymphoma (MZL), Mantle Cell Lymphoma (MCL), and Waldenström macroglobulinemia (WM), between 01-Jan-2008 and 31-Dec-2013, until 31-Dec-2017. Treatment pathways were modelled using a Markov approach. Stage III/IV disease at diagnosis was frequent for patients with DLBCL, FL, MCL and WM. Hepatitis B surface antigen/hepatitis C virus seropositivity was 18.6%/12.3%. Clinical responses to 1st-line treatment were observed in 76.0% (DLBCL), 87.3% (FL), 86.0% (MZL), 60.0% (MCL), and 42.9% (WM) of patients. For DLBCL, disease control was achieved by ~ 50% after 1st-line, ~ 24% after 2nd-line, ~ 17% after 3rd-line. Patients with Stage III/IV DLBCL or age > 65 years at diagnosis had lower rates of active treatment, poorer disease control and higher mortality than patients with early stage disease or age ≤ 65 years. Disease flare < 6 months after 1st-line treatment was significantly associated with mortality. Despite good clinical response rates for some sub-types, survival remains poor. New treatments are needed to improve the outcome of B-NHL.
The positive association between the total duration of physical activity and performances of physical function may vary at different times of the day as circadian rhythm regulates individuals in ...response to external stimulations. We aimed to examine the association of timing-specific and overall moderate-to-vigorous physical activity (MVPA) with performances of physical function in older adults. A cross-sectional analysis was conducted among 118 older adults (mean age = 70.0 ± 5.0 years). We assessed and identified timing-specific (morning: 06:01-12:00; afternoon: 12:01-18:00; evening: 18:01-24:00) and overall MVPA using a triaxial accelerometer. Different measures of physical function were evaluated including handgrip strength (by grip dynamometer), gait speed (5-m walk test), basic functional mobility (timed up and go test), and lower limb strength (five times sit-to-stand test). Multivariate linear regression models adjusting for covariates were used to investigate the associations. Participants spent 25.0 (± 26.2) minutes in MVPA per day on average, half the time spent during the morning (47.7%), followed by during the afternoon (29.9%) and evening (21.6%). The time spent on overall MVPA was generally associated with better physical function performances. There was statistical evidence for the percentages of MVPA engagement during the morning B = 0.214, 95% confidence interval (CI) 0.001 to 0.428 and afternoon (B = - 0.273, 95% CI - 0.518 to - 0.027) associated with basic functional mobility but with contrary directions; the percentage of MVPA engagement during the evening was associated with less time spent in gait speed performance (B = - 0.237, 95% CI - 0.468 to - 0.006). Our findings inform implications that the overall MVPA engagement was more important than timing-specific MVPA to older adults' physical function performances. Strategies for accumulating time of MVPA is more practical and effective than encouraging to engage MVPA in specific timing for the enhancement of functional ability and therefore prevent disability among older adults.
A limited number of studies have used objective measures to examine the associations between the built environment and physical activity (PA) among older adults. This study aimed to examine ...geographic information systems-derived neighborhood walkability attributes and accelerometer measured PA in older adults. Data were collected from 124 older Taiwanese adults aged over 60 years (mean age: 69.9). Adjusted multiple linear regression was performed to explore the associations between five neighborhood walkability factors (population density, street connectivity, sidewalk availability, access to destinations, and public transportation) and five metrics of accelerometer-measured physical activity (total PA, moderate-to-vigorous PA, light PA, long moderate-to-vigorous PA bouts, and daily step counts). After adjusting for potential confounders, we found that greater sidewalk availability was positively associated with daily step counts in older adults (β = 0.165; 95% confidence interval: 0.006, 0.412; P = 0.043). No associations between other neighborhood environment attributes and PA metrics were observed. In conclusion, high sidewalk availability in the neighborhood may be supportive for older adults' daily step counts. Further longitudinal research is needed to establish the causality between the built environment and objectively measured PA in older adults.
MicroRNAs (miRNAs), which are inhibitors of gene expression, participate in diverse biological functions and in carcinogenesis. In this study, we show that liver‐specific microRNA‐122 (miR‐122) is ...significantly down‐regulated in liver cancers with intrahepatic metastastasis and negatively regulates tumorigenesis. Restoration of miR‐122 in metastatic Mahlavu and SK‐HEP‐1 cells significantly reduced in vitro migration, invasion, and anchorage‐independent growth as well as in vivo tumorigenesis, angiogenesis, and intrahepatic metastasis in an orthotopic liver cancer model. Because an inverse expression pattern is often present between an miRNA and its target genes, we used a computational approach and identified multiple miR‐122 candidate target genes from two independent expression microarray datasets. Thirty‐two target genes were empirically verified, and this group of genes was enriched with genes regulating cell movement, cell morphology, cell‐cell signaling, and transcription. We further showed that one of the miR‐122 targets, ADAM17 (a disintegrin and metalloprotease 17) is involved in metastasis. Silencing of ADAM17 resulted in a dramatic reduction of in vitro migration, invasion, in vivo tumorigenesis, angiogenesis, and local invasion in the livers of nude mice, which is similar to that which occurs with the restoration of miR‐122. Conclusion: Our study suggests that miR‐122, a tumor suppressor microRNA affecting hepatocellular carcinoma intrahepatic metastasis by angiogenesis suppression, exerts some of its action via regulation of ADAM17. Restoration of miR‐122 has a far‐reaching effect on the cell. Using the concomitant down‐regulation of its targets, including ADAM17, a rational therapeutic strategy based on miR‐122 may prove to be beneficial for patients with hepatocellular carcinoma. (HEPATOLOGY 2009.)
Introduction
The association of light‐intensity physical activity (LPA) with mortality is poorly understood. This meta‐analysis of cohort studies aimed to examine the dose‐response relationships ...between daily device‐measured LPA and mortality in adults aged 18 or older and to explore whether the associations were independent of moderate‐to‐vigorous physical activity (MVPA).
Methods
Searches for prospective cohort studies providing effect estimates of daily LPA (exposure) on all‐cause mortality (outcome) were systematically undertaken in electronic databases up to April 30, 2019. Subgroup analyses and meta‐regression analyses with random‐effects models were performed to quantify the dose‐response relationships between daily LPA and mortality. Sensitivity analyses were also conducted to assess the stability of the results.
Results
A total of 11 studies were included in the meta‐analysis. Analyses contained 49 239 individuals (mean age 60.7, SD = 13.6) who were followed up for a mean 6.2 years (2.3‐14.2 years), during which 3669 (7.5%) died. In comparison with the reference group (<3 h/d), the pooled HRs (and 95% CIs) of mortality were 0.71 (0.62‐0.82), 0.68 (0.59‐0.79), 0.56 (0.44‐0.71) for groups 3 to <5 h/d, 5 to <7 h/d, and more than 7 hours a day LPA, respectively. Meta‐regression models indicated that there was a log‐cubic dose‐response relationship between daily LPA and mortality in adults and older people, independent of MVPA.
Conclusions
Time spent in daily LPA was associated with reduced risks of mortality in adults and older people. These data support the inclusion of LPA in the future physical activity guidelines.
Abstract
Aim
Alpha‐fetoprotein (AFP) checkup with abdominal ultrasonography for hepatocellular carcinoma (HCC) surveillance remains controversial. We evaluated a serial AFP‐increase and high AFP ...levels in the prediction of HCC.
Methods
At‐risk patients with chronic liver disease underwent HCC surveillance with trimonthly AFP measurement were included and categorized into HCC and non‐HCC groups. Their AFP levels at 12, 9, and 6 months (−6M) before the outcome date were evaluated. Group‐based trajectory analysis and multivariable regression analysis were performed to identify AFP trajectories as risk predictors for HCC.
Results
Overall, 2776 patients were included in the HCC (
n
= 326) and non‐HCC (
n
= 2450) groups. Serial AFP levels were significantly higher in the HCC than the non‐HCC groups. Trajectory analysis identified AFP‐increase group (11%) increased 24‐fold risks of HCC compared with the AFP‐stable (89%) group. Compared with patients without the AFP‐increase, a serial 3‐month AFP‐increase ≥10% elevated HCC risk by 12.1‐fold (95% CI: 6.5–22.4) in 6 months, and the HCC risks increased 13–60 fold in patients with cirrhosis, hepatitis B, or C receiving antiviral therapy, or AFP levels <20 ng/ml. Combining serial AFP‐increase ≥10% and AFP ≥20 ng/ml at −6M significantly increased 41.7‐fold (95% CI: 13.8–126.2) HCC risks. In patients who underwent biannual AFP checkups, those with both 6‐month AFP‐increase ≥10% and AFP ≥20 ng/ml increased 22.1‐fold (95% CI: 12.52–39.16) HCC risks in 6 months. Most HCCs were detected at an early stage.
Conclusions
Serial 3–6‐month AFP‐increase of ≥10% previously and AFP level of ≥20 ng/ml significantly increased HCC risks in 6 months.
Background: The impact of meeting leisure-time physical activity (LTPA) recommendations and household physical activity (HPA) on all-cause mortality in the Taiwanese population is unclear. We aimed ...to investigate the relationship between sufficient LTPA and all-cause mortality in middle-aged and older Taiwanese adults and the role of HPA in those with insufficient LTPA.Methods: This nationwide prospective cohort study included 4,960 participants aged ≥50 years from the Taiwan Longitudinal Study in Aging (TLSA) survey. Physical activity patterns were assessed in 2003 and then followed up until 2015 for mortality through the National Death Registration Record. Cox proportional hazards regression was conducted to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality.Results: Of the 4,960 participants, 1,712 died of all-cause mortality. Compared to those who had insufficient LTPA, participants who engaged in sufficient LTPA showed a significantly lower risk of all-cause mortality (HR = 0.84, 95% CI, 0.73–0.97). For those with insufficient LTPA, HPA also had a significantly reduced risk of all-cause mortality (HR = 0.85, 95% CI, 0.75–0.96) among general population. Similar associations were observed in subsequent sensitivity analyses. The subgroup analysis showed that the relationship between HPA and reduced mortality risk was only found in the women with insufficient LTPA group.Conclusion: This study confirmed that sufficient LTPA is associated with a lower risk of all-cause mortality. If sufficient LTPA cannot be performed, additional HPA is related to lower mortality.
Nevus sebaceus is frequently associated with the development of secondary neoplasms. Incidences of malignant transformation vary among different reports and few data is available regarding Asian ...populations. We aimed to determine the characteristics of secondary tumors developing from nevus sebaceus in a Taiwanese population and to review the published work. Patients with clinically and histologically confirmed nevus sebaceus were identified from 1992 to 2012 in a medical center. Among the 450 cases of nevus sebaceus, 38 secondary neoplasms were noted, accounting for 8.5% of all cases. Benign tumors represented more than 80% of all tumors. Syringocystadenoma papilliferum (2.7%) was the most common benign tumor, followed by trichoblastoma (1.6%) and trichilemmoma (1.6%) whereas basal cell carcinoma (0.9%) was the most frequent malignant tumor on nevus sebaceus and its clinical features were not typical. All the malignant tumors on nevus sebaceus were noted only in adulthood and the mean age of those with basal cell carcinoma was significantly older than that of trichoblastoma (P = 0.028). Our study concludes that malignant transformation is rare in nevus sebaceus and occurs uniquely in adulthood. On the basis of the findings, prophylactic excision of nevus sebaceus can be elective during childhood but is strongly advocated at puberty due to the increased risk of malignant transformation with time.
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