Background & Aims
Differentiation antagonizing non‐protein coding RNA is associated with various types of neoplasms. Hepatitis C virus‐related hepatocellular carcinoma has a high risk of recurrence. ...Here we determined the role of differentiation antagonizing non‐protein coding RNA in hepatitis C virus‐related hepatocarcinogenesis and identified potential therapeutic targets and non‐invasive prognostic markers for long‐term outcome of hepatitis C virus‐related hepatocellular carcinoma after surgical resection.
Methods
Differentiation antagonizing non‐protein coding RNAs relevant to hepatitis C virus‐related hepatocellular carcinoma were identified through comparative RNA‐sequencing of tumour and adjacent non‐tumour (ANT) tissues in a screening set, and were validated using real‐time polymerase chain reaction. Target long non‐coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus‐related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012.
Results
We confirmed that differentiation antagonizing non‐protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus‐related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus‐related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non‐protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3‐11.6 and 2.7/1.5‐5.1 respectively).
Conclusions
Differentiation antagonizing non‐protein coding RNA is highly relevant to disease progression of hepatitis C virus‐related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non‐protein coding RNA might serve as a non‐invasive prognostic biomarker for hepatitis C virus‐related hepatocellular carcinoma.
Aims
To investigate whether metabolic syndrome (MetS) could predict renal outcome in patients with established chronic kidney disease (CKD).
Materials and Methods
We enroled 2500 patients with CKD ...stage 1–4 from the Integrated CKD care programme, Kaohsiung for delaying Dialysis (ICKD) prospective observational study. 66.9% and 49.2% patients had MetS and diabetes (DM), respectively. We accessed three clinical outcomes, including all‐cause mortality, RRT, and 50% decline in estimated glomerular filtration rate events.
Results
The MetS score was positively associated with proteinuria, inflammation, and nutrition markers. In fully adjusted Cox regression, the hazard ratio (HR) (95% confidence interval) of MetS for composite renal outcome (renal replacement therapy, and 50% decline of renal function) in the DM and non‐DM subgroups was 1.56 (1.15–2.12) and 1.31 (1.02–1.70), respectively, while that for all‐cause mortality was 1.00 (0.71–1.40) and 1.27 (0.92–1.74). Blood pressure is the most important component of MetS for renal outcomes. In the 2 by 2 matrix, compared with the non‐DM/non‐MetS group, the DM/MetS group (HR: 1.62 (1.31–2.02)) and the non‐DM/MetS group (HR: 1.33 (1.05–1.69)) had higher risks for composite renal outcome, whereas the DM/MetS group had higher risk for all‐cause mortality (HR: 1.43 (1.09–1.88)).
Conclusions
MetS could predict renal outcome in patients with CKD stage 1–4 independent of DM.
This study investigated whether melatonin‐treated adipose‐derived mesenchymal stem cells (ADMSC) offered superior protection against acute lung ischemia–reperfusion (IR) injury. Adult male ...Sprague‐Dawley rats (n = 30) were randomized equally into five groups: sham controls, lung IR–saline, lung IR–melatonin, lung IR–melatonin–normal ADMSC, and lung IR–melatonin–apoptotic ADMSC. Arterial oxygen saturation was lowest in lung IR–saline; lower in lung IR–melatonin than sham controls, lung IR–melatonin–normal ADMSC, and lung IR–melatonin–apoptotic ADMSC; lower in lung IR–melatonin–normal ADMSC than sham controls and lung IR–melatonin–apoptotic ADMSC; lower in lung IR–melatonin–apoptotic ADMSC than sham controls (P < 0.0001 in each case). Right ventricular systolic blood pressure (RVSBP) showed a reversed pattern among all groups (all P < 0.0001). Changes in histological scoring of lung parenchymal damage and CD68+ cells showed a similar pattern compared with RVSBP in all groups (all P < 0.001). Changes in inflammatory protein expressions such as VCAM‐1, ICAM‐1, oxidative stress, TNF‐α, NF‐κB, PDGF, and angiotensin II receptor, and changes in apoptotic protein expressions of cleaved caspase 3 and PARP, and mitochondrial Bax, displayed identical patterns compared with RVSBP in all groups (all P < 0.001). Numbers of antioxidant (GR+, GPx+, NQO‐1+) and endothelial cell biomarkers (CD31+ and vWF+) were lower in sham controls, lung IR–saline, and lung IR–melatonin than lung IR–melatonin–normal ADMSC and lung IR–melatonin–apoptotic ADMSC, and lower in lung IR–melatonin–normal ADMSC than lung IR–melatonin–apoptotic ADMSC (P < 0.001 in each case). In conclusion, when the animals were treated with melatonin, the apoptotic ADMSC were superior to normal ADMSC for protection of lung from acute IR injury.
Dengue virus (DENV) infection is a serious global health issue as it causes severe dengue hemorrhagic fever and dengue shock syndrome. Since no approved therapies are available to treat DENV ...infection, it is necessary to develop new agents or supplements that can do this. In this study, grape seed proanthocyanidins extract (GSPE), which is widely consumed as a dietary supplement, dose-dependently suppressed the replication of four DENV serotypes. The inhibitory mechanism demonstrated that GSPE downregulated DENV-induced aberrant cyclooxygenase-2 (COX-2) expression, revealing that the inhibitory effect of the GSPE on DENV replication involved targeting DENV-induced COX-2 expression. Mechanistic studies on signaling regulation have demonstrated that GSPE significantly reduced COX-2 expression by inactivating NF-κB and ERK/P38 MAPK signaling activities. Administrating GSPE to DENV-infected suckling mice reduced virus replication, mortality, and monocyte infiltration of the brain. In addition, GSPE substantially reduced the expression of DENV-induced inflammatory cytokines associated with severe dengue disease, including tumor necrosis factor-α, nitric oxide synthase, interleukin (IL)-1, IL-6, and IL-8, suggesting that GSPE has potential as a dietary supplement to attenuate DENV infection and severe dengue.
Hepatocellular carcinoma (HCC) is considered to be a silent killer, and was the fourth leading global cause of cancer deaths in 2018. For now, sorafenib is the only approved drug for advanced HCC ...treatment. The introduction of additional chemopreventive agents and/or adjuvant therapies may be helpful for the treatment of HCC. After screening 3000 methanolic extracts from the Formosan plant extract bank,
showed glycine
-methyltransferase (GNMT)-promoter-enhancing and nuclear factor erythroid 2-related factor 2 (NRF2)-suppressing activities. Further, the investigation of the whole plant of
led to the isolation of a new steroid, 7α-hydroperoxysitosterol-3-
-β-d-(6-
-palmitoyl)glucopyranoside (
); two new coumarinolignans, excoecoumarin A (
) and excoecoumarin B (
); a new diterpene, excoeterpenol A (
); and 40 known compounds (
-
). Among them, Compounds
and
-
at a 100 μM concentration showed a 2.97 ± 0.27-, 3.17 ± 1.03-, 2.73 ± 0.23-, 2.63 ± 0.14-, 6.57 ± 0.13-, and 2.62 ± 0.05-fold increase in GNMT promoter activity, respectively. In addition, Compounds
and
could reduce NRF2 activity, a transcription factor associated with drug resistance, in Huh7 cells with relative activity of 33.1 ± 0.2% and 45.2 ± 2.5%. These results provided the basis for the utilization of Taiwan agarwood for the development of anti-HCC agents.
Background
Nutritional counseling is frequently overlooked in cancer patients with normal nutritional status. This study aimed to evaluate the impact of nutritional counseling in head and neck cancer ...(HNC) patients with normal nutritional status prior to concurrent chemoradiotherapy (CCRT).
Methods
A total of 243 patients with pretreatment normal nutritional status and locally advanced HNC receiving concurrent chemoradiotherapy (CCRT) at three medical centers were enrolled. All patients were retrospectively allocated into the early (≤ 2 weeks,
n
= 105, 43.2%), late (> 2 weeks,
n
= 102, 42.0%), and no nutritional counseling groups (
n
= 36, 14.8%) according to the time interval between the date of CCRT initiation and the first date of nutritional counseling for comparison.
Results
The 1-year overall survival rates were 95.0%, 87.5%, and 81.3% in the early, late, and no nutritional counseling groups (
p
= 0.035), respectively. The median body weight changes at end of CCRT were − 4.8% (range, − 13.3 to 8.7%), − 5.6% (range, − 21.9 to 5.6%), and − 8.6% (range, − 20.3 to 2.4%) in patients in the early, late, and no nutritional counseling groups, respectively. The early termination of chemotherapy rates and the incompletion rates of planned radiotherapy were 1.9% and 1.9%, 2.9%, and 2.0%, 13.9%, and 19.4% in patients in the early, late, and no nutritional counseling groups, respectively.
Conclusions
Our findings strongly suggest that while some HNC patients may have pretreatment normal nutritional status, early nutritional counseling is nevertheless essential for the improvement of treatment tolerance and survival outcome.
is most commonly used as a traditional herb medicine in Taiwan. In this study, high performance liquid chromatography equipped with photodiode array detection-mass (HPLC-DAD-ESI-MS) method was ...developed for the identification and quantification of bioactive phenolics. The developed method was also validated for accuracy, precision, limit of detection, and quantification. In this method, chlorogenic acid, rutin, isoquercetrin, nictoflorin, astragalin, and quercetin were quantified in linearity range of 10-100 (μg/mL) with a correlation coefficient of greater than 0.996. High recovery (86.5-93.1%) and good reproducibility were obtained for six phenolics with the relative standard deviation ranging from 1.7-3.1%. Therefore, the proposed method for simultaneous quantification of six bioactive phenolics in the extract and fractions of
using HPLC-DAD-ESI-MS detection under the optimized conditions is accurate and validated. Among the results, methanol extract showed the greatest values of total phenolic content (93.1 mg gallic acid equivalent/g). Additionally, the methanol extract revealed best antioxidant capacity based on the DPPH scavenging activity and anti-glycation activity (IC
was observed at 97.1 and 77.9 μg/mL, respectively).
Continuing chemical investigation of the Red Sea sponge
sp. led to the isolation of four new 3,4-
-3,19-dinorspongian diterpenoid lactones, secodinorspongins A-D (
-
), along with a classical ...spongian diterpenoid lactone, sponginolide (
). The chemical structures, including the absolute configurations of these compounds, were elucidated using the extensive spectroscopic study composed of 1D and 2D NMR data analyses, and a comparison between calculated-electronic-circular-dichroism (ECD) and experimental-circular-dichroism (CD) spectra. A plausible biosynthetic pathway of
-
was also proposed. Furthermore, the cytotoxicity, antibacterial and anti-inflammatory activities of
-
were evaluated. Compound
was found to exhibit inhibitory activity against the growth of
(
), and
and
exhibited suppression of superoxide-anion generation and elastase release in fMLF/CB-induced human neutrophils.
L. (saffron) has been traditionally used as a food coloring or flavoring agent, but recent research has shown its potent pharmacological activity to tackle several health-related conditions.
sp. ...leaves, and petals are the by-products of saffron production and are not usually used in the medicine or food industries. The present study was designed to determine the chemical composition of the water and ethanolic extracts of
leaves and test their cytotoxic activity against melanoma (IGR39) and triple-negative breast cancer (MDA-MB-231) cell lines by MTT assay. We also determined their anti-allergic, anti-inflammatory, and anti-viral activities. HPLC fingerprint analysis showed the presence of 16 compounds, including hydroxycinnamic acids, xanthones, flavonoids, and isoflavonoids, which could contribute to the extracts' biological activities. For the first time, compounds such as tectoridin, iristectorigenin B, nigricin, and irigenin were identified in
leaf extracts. The results showed that mangiferin (up to 2 mg/g dry weight) and isoorientin (8.5 mg/g dry weight) were the major active ingredients in the leaf extracts. The ethanolic extract reduced the viability of IGR39 and MDA-MB-231 cancer cells with EC
= 410 ± 100 and 330 ± 40 µg/mL, respectively. It was more active than the aqueous extract. Kaempferol and quercetin were identified as the most active compounds. Our results showed that
leaves contain secondary metabolites with potent cytotoxic and antioxidant activities.
Background and Aim
Given that a wide variation in tumor response rates and survival times suggests heterogeneity among the patients with advanced pancreatic cancer (APC) who underwent second‐line ...(L2) chemotherapy, it is a challenge in clinical practice to identify patients who will receive the most benefit from L2 treatment.
Methods
We selected 183 APC patients who received L2 palliative chemotherapy between 2010 and 2016 from a medical center as the development cohort. A Cox proportional hazard model was used to identify the prognostic factors and construct the nomogram. An independent cohort of 166 patients from three other hospitals was selected for external validation.
Results
The nomogram was based on eight independent prognostic factors from the multivariate Cox model: sex, Eastern Cooperative Oncology Group performance status, reason for first‐line treatment discontinuation, duration of first‐line treatment, neutrophil‐to‐lymphocyte ratio, tumor stage, body mass index, and serum carbohydrate antigen 19‐9 levels at the beginning of L2 treatment. The model exhibited good discrimination ability, with a C‐index of 0.733 (95% confidence interval, 0.681–0.785) and 0.724 (95% confidence interval, 0.661–0.787) in the development and validation cohorts, respectively. The calibration plots of the development and validation cohorts showed optimal agreement between model prediction and actual observation in predicting survival probability at 6 months, 1 year, and 2 years.
Conclusions
This study developed and externally validated a prognostic model that accurately predicts the survival outcome of APC patients before L2 palliative chemotherapy, which could assist in clinical decision‐making, counseling for treatment, and most importantly, prognostic stratification of patients.
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