Anti-angiogenic properties of microRNA-29a in preclinical ocular models.

Abnormal neovascularization is an important cause of blindness in many ocular diseases, for which the etiology and pathogenic mechanisms remain incompletely understood. Recent studies have revealed the diverse roles of noncoding RNAs in various biological processes and facilitated the research and development of the clinical application of numerous RNA drugs, including microRNAs. Here, we report the antiangiogenic activity of microRNA-29a (miR-29a) in three animal models of ocular neovascularization. The miR-29a knockout (KO) mice displayed enhanced vessel pruning, resulting in a decreased vascularized area during retinal development. In contrast, miR-29a deletion in adult mice accelerated angiogenesis in preclinical disease models, including corneal neovascularization, oxygen-induced retinopathy, and choroidal neovascularization, while the administration of agomir-29a ameliorated pathological neovascularization. Furthermore, miR-29a exerted inhibitory effects on endothelial cell proliferation, migration, and tube formation capacities. RNA sequencing analysis of retinas from miR-29a KO mice and RNA interference experiments identified platelet-derived growth factor C and several extracellular matrix genes as downstream targets of miR-29a involved in regulating ocular angiogenesis. Our data suggest that miR-29a may be a promising clinical candidate for the treatment of neovascular diseases.

Orbital Interactions in 2D Dion-Jacobson Perovskites Using Oligothiophene-Based Semiconductor Spacers Enable Efficient Solar Cells.

2D Dion-Jacobson (DJ) perovskites have emerged as promising photovoltaic materials, but the insulating organic spacer has hindered the efficient charge transport. Herein, we successfully synthesized a terthiophene-based semiconductor spacer, namely, 3ThDMA, for 2D DJ perovskite. An interesting finding is that the energy levels of 3ThDMA extensively overlap with the inorganic components and directly contribute to the band formation of (3ThDMA)PbI4, leading to enhanced charge transport across the organic spacer layers, whereas no such orbital interactions were found in (UDA)PbI4, a DJ perovskite based on 1,11-undecanediaminum (UDA). The devices based on (3ThDMA)MAn-1PbnI3n+1 (nominal n = 5) obtained a champion efficiency of 15.25%, which is a record efficiency for 2D DJ perovskite solar cells using long-conjugated spacers (conjugated rings ≥ 3) and a 22.60% efficiency for 3ThDMA-treated 3D PSCs. Our findings provide an important insight into understanding the orbital interactions in 2D DJ perovskite using an organic semiconductor spacer for efficient solar cells.

Association between serum copper levels and stroke in the general population: A nationally representative study.

OBJECTIVES: The objective was to explore the association between serum copper levels and the prevalence of stroke. METHODS: Data were obtained from 3 consecutive National Health and Nutrition Examination Survey (NHANES) cycles (2011-2016). Weighted multivariable logistic regression analysis was conducted to evaluate the association between serum copper levels and self-reported stroke. RESULTS: A total of 5,151 adults met the inclusion criteria. A total of 181 (3.51%) stroke patients were identified. In comparison to individuals with serum copper levels in the lowest tertile (<16.4 µmol/l), those with levels in the middle tertile (16.4-19.8 µmol/l) had an odds ratio (OR) of 0.99 (95% confidence interval [CI]: 0.44-2.25), while those with levels in the highest tertile (>19.8 µmol/l) had an OR of 2.36 (95% CI: 1.01-5.52). Furthermore, each standard deviation (SD) increase in serum copper was found to be positively associated with the prevalence of stroke, with an OR of 1.44 (95% CI: 1.11-1.86). Dose‒response analysis showed a positive linear association between serum copper levels and stroke (Pnonlinearity=0.554). CONCLUSIONS: This cross-sectional study suggested a positive association between serum copper levels and stroke among American adults.

Association between triglyceride glucose index and arterial stiffness and coronary artery calcification: a systematic review and exposure-effect meta-analysis.

BACKGROUND: The triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC). METHODS: We conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship. RESULTS: Twenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55-2.17, I2 = 68%) and CAC (OR: 1.66; 95% CI 1.51-1.82, I2 = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35-1.69, I2 = 82%) and CAC (OR: 1.73, 95% CI 1.36-2.20, I2 = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21-2.27, I2 = 0, in category analysis, OR = 1.47, 95% CI 1.29-1.68, I2 = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (Pnonlinearity < 0.001). CONCLUSION: An elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality.

Glycated albumin and risk of cardiovascular diseases and mortality in patients with and without dialysis: A meta-analysis.

BACKGROUND: Several studies have shown that glycated albumin (GA) is a more accurate measure of short-term blood sugar control in patients with dialysis. We aim to investigate the relationship between GA and the risk of cardiovascular diseases (CVDs) and mortality in patients both with and without dialysis. MATERIALS AND METHODS: We searched cohort studies of associations between GA level and CVD and mortality in PubMed, Cochrane Library and Embase databases. The effect size was summarized by the random effects model, and the dose-response association was determined by robust error meta-regression method. RESULTS: This meta-analysis included data from 80 024 participants in 17 cohort studies, 12 of which were prospective and five were retrospective. The results showed that higher levels of GA were associated with increased risk of CV mortality [hazard ratio = 1.90; 95% confidence interval (CI) 1.22-2.98], all-cause mortality (hazard ratio = 1.64; 95% CI 1.41-1.90), major adverse cardio-cerebral events (risk ratio = 1.41; 95% CI 1.17-1.71), coronary artery disease (odds ratio = 2.24; 95% CI 1.75-2.86) and stroke (risk ratio = 1.72; 95% CI 1.24-2.38). The dose-response analysis showed that GA levels were positively and linearly associated with the risk of CV mortality (p = .38), all-cause mortality (p = .57) and coronary artery disease (p = .18). Subgroup analysis showed that high levels of GA were associated with the risk of CV and all-cause mortality, regardless of dialysis status, with significant differences between subgroups of dialysis (CV mortality: p = .02; all-cause mortality: p = .03). CONCLUSION: High GA levels are associated with an increased risk of CVDs and mortality, regardless of dialysis status.

Association of serum copper (Cu) with cardiovascular mortality and all-cause mortality in a general population: a prospective cohort study.

BACKGROUND: Copper (Cu) homeostasis and Cu-induced cell death are gaining recognition as crucial processes in the pathogenesis of cardiovascular disease (CVD). Circulating Cu associated with CVD and mortality is yet to be fully elucidated. OBJECTIVE: This national prospective cohort study is to estimate relationship between serum Cu and the risk of CVD and all-cause mortality. METHODS: This study included participants from the National Health and Nutrition Examination Survey 2011-2016. Weighted Cox proportional hazards regression analysis and exposure-response curves were applied. RESULTS: This included 5,412 adults, representing 76,479,702 individuals. During a mean of 5.85 years of follow-up (31,653 person-years), 96 CVD and 356 all-cause mortality events occurred. Age and sex-adjusted survival curves showed that individuals with higher levels of serum Cu experienced increased CVD and all-cause death rates (tertiles, p < 0.05). Compared with the participant in tertile 1 of serum Cu (< 16.31 mol/L), those in tertile 3 (≥ 19.84 mol/L) were significantly associated with CVD mortality (HR: 7.06, 95%CI: 1.85,26.96), and all-cause mortality (HR: 2.84, 95% CI: 1.66,4.87). The dose-response curve indicated a linear relationship between serum Cu and CVD mortality (p -nonlinear = 0.48) and all-cause (p -nonlinear = 0.62). A meta-analysis included additional three prospective cohorts with 13,189 patients confirmed the association between higher serum Cu and CVD (HR: 2.08, 95% CI: 1.63,2.65) and all-cause mortality (HR: 1.89, 95%CI: 1.58,2.25). CONCLUSION: The present study suggests excessive serum Cu concentrations are associated with the risk of CVD and all-cause mortality in American adults. Our findings and the causal relationships require further investigation.

The role of stimulator of interferon genes-mediated AMPK/mTOR/P70S6K autophagy pathway in cyfluthrin-induced testicular injury.

Cyfluthrin is widely used in the field of sanitary pest control by its wide insecticidal spectrum, high efficiency and low toxicity, low residue, and good biodegradability. But, as a double-edged sword, a large amount of cyfluthrin remains are still in the environment. The residual cyfluthrin is absorbed into the food chain through vegetation and then poses a risk to soil organisms and human health. Several studies have suggested that cyfluthrin is one of the main factors causing testicular damage, but the mechanism remains unclear. In this study, we established in vivo and in vitro models of testicular injury in rats and GC-2 cells exposed to cyfluthrin to explore whether stimulator of interferon genes (STING) gene mediates the regulation of AMPK/mTOR/p70S6K autophagy pathway, which lays a foundation for further study of the mechanism of testicular injury induced by cyfluthrin. The results showed that the activity of super oxide dismutase in testis decreased and the activity of malonic dialdehyde increased with the increase of concentration in vivo and in vitro. At the same time, the levels of mitochondrial damage and inflammation in the testis also increased, which further activated autophagy. In this process, the increased level of inflammation is related to the increased expression of STING gene, and AMPK/mTOR/p70S6K autophagy pathway is also involved. To sum up, cyfluthrin has certain reproductive toxicity, and long-term exposure can induce testicular cell damage. STING gene can participate in cyfluthrin-induced testicular injury through AMPK/mTOR/P70S6K autophagy pathway.

Nucleation and Crystallization in 2D Ruddlesden-Popper Perovskites using Formamidinium-based Organic Semiconductor Spacers for Efficient Solar Cells.

The conjugated organic semiconductor spacers have drawn wide attention in two-dimensional (2D) perovskites and formamidinium (FA) has been widely used as A-site cation in high-performance 3D perovskite solar cells (PSCs). However, the FA-based semiconductor spacers have rarely been investigated in 2D Ruddlesden-Popper (RP) perovskites. Here, we developed two FA-based spacers containing thieno[3,2-b]thiophene (TT) and 2,2'-bithiophene (BT) units, namely TTFA and BTFA, respectively, for 2D RP PSCs. The nucleation and crystallization kinetics of TTFA-Pb and BTFA-Pb from sol-gel to film were investigated using in situ optical microscopy and in situ grazing incidence wide-angle X-ray scattering (GIWAXS) measurements. It is found that the TTFA spacer could reduce the energy barrier of nucleation and induces crystal vertical orientation of 2D perovskite by forming larger clusters in precursor solution, resulting in much improved film quality. Benefiting from the enlarged crystal grains, reduced exciton binding energy, and decreased electron-phonon coupling coefficient, the photovoltaic device based on (TTFA)2 MAn-1 Pbn I3n+1 (n=5) achieved a champion efficiency of 19.41 %, which is a record for 2D RP PSCs with FA-based spacers. Our work provides deep understanding of the nucleation and crystallization process of 2D RP perovskite films and highlights the great potential of FA-based semiconductor spacers in highly efficient 2D PSCs.

Low prognostic nutritional index is associated with poor outcome in middle-aged and elderly patients with non-metastatic nasopharyngeal carcinoma: a retrospective cohort study.

BACKGROUND: Prognostic nutritional index (PNI) and age are effective prognostic factors for patients with non-metastatic nasopharyngeal carcinoma (NPC), and an interaction between them may exist. However, the age cutoff value is generally set at 45 years in current studies. The clinical implications of PNI in middle-aged and elderly patients are unclear. Therefore, we aimed to uncover this issue. PATIENTS AND METHODS: We retrospectively collected data from 132 middle-aged and elderly (≥ 45 years old) patients with non-metastatic NPC. The association between covariates and the PNI was analyzed using 2 or t-test. The effect of PNI on the prognosis was evaluated using univariate and multivariate Cox regression analyses. Unadjusted and multivariate-adjusted models were applied. Stratified and interactive analyses were performed to investigate the potential source of heterogeneity. RESULTS: Median age (61.0 years versus 59.5 years) and the proportion of patients aged ≥ 60 years (57.6% versus 50.0%) in the low-PNI group were higher than those in the high-PNI group (P > 0.05). The patients with a low PNI had shorter overall survival (OS) (hazard ratio (HR) = 0.86, 95% confidence interval (CI) = 0.80-0.93; P < 0.001) and progression-free survival (PFS) (HR = 0.93, 95% CI = 0.87-0.99; P = 0.034). The results remained stable after three adjusted models of covariates, including age (P < 0.05). No significant interactions were observed in middle-aged (45-59 years) and elderly (≥ 60 years) subgroups for OS and PFS (P for interaction > 0.05). CONCLUSION: Although there is an interaction between PNI and age, PNI is an independent prognostic factor in middle-aged and elderly patients with non-metastatic NPC.

[Internal circadian clock and liver metabolism].

Circadian clock is an internal autonomous time-keeping system, including central clocks located in the suprachiasmatic nucleus (SCN) and peripheral clocks. The molecular circadian clock consists of a set of interlocking transcriptional-translational feedback loops that take the clock-controlled genes 24 h to oscillate. The core mechanism of molecular circadian clock is that CLOCK/BMAL1 dimer activates the transcription of cryptochromes (CRYs) and Periods (PERs), which act as transcriptional repressors of further CLOCK/BMAL1-mediated transcription. In addition to this basic clock, there is an additional sub-loop of REV-ERBα and RORα regulating the transcription of BMAL1. Approximately 80% protein-coding genes demonstrate significant rhythmicity. The earth rotation is responsible for the generation of the daily circadian rhythms. To coordinate metabolic balance and energy availability, almost all organisms adapt to the rhythm. Studies have shown that circadian clock integrating with metabolic homeostasis increases the efficiency of energy usage and coordinates with different organs in order to adapt to internal physiology and external environment soon. As the central organ of metabolism, the liver performs various physiological activities nearly all controlled by the circadian clock. There are multiple interactive regulation mechanisms between the circadian clock and the regulation of liver metabolism. The misalignment of metabolism with tissue circadian is identified as a high-risk factor of metabolic diseases. This article reviews the recent studies on circadian physiological regulation of liver glucose, lipid and protein metabolism and emphasizes oscillation of mitochondrial function. We also take an outlook for new methods and application of circadian clock research in the future.

Endovascular hypothermia improves post-resuscitation myocardial dysfunction by increasing mitochondrial biogenesis in a pig model of cardiac arrest.

The aim of the study was to investigate the effects of endovascular hypothermia on mitochondrial biogenesis in a pig model of prolonged cardiac arrest (CA). Ventricular fibrillation was electrically induced, and animals were left untreated for 10 min; then after 6min of cardiopulmonary resuscitation (CPR), defibrillation was attempted. 25 animals that were successfully resuscitated were randomized into three groups: Sham group (SG, 5, no CA), normal temperature group (NTG, 5 for 12 h observation and 5 for 24 h observation), and endovascular hypothermia group (EHG, 5 for 12 h observation and 5 for 24 h observation). The core temperatures (Tc) in the EHG were maintained at 34 ±â€¯0.5 °C for 6 h by an endovascular hypothermia device (Coolgard 3000), then actively increased at the speed of 0.5 °C per hour during the next 6 h to achieve a normal body temperature, while Tc were maintained at 37.5 ±â€¯0.5 °C in the NTG. Cardiac and mitochondrial functions, the quantification of myocardial mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, and NRF-2 were examined. Results showed that myocardial and mitochondrial injury and dysfunction increased significantly at 12 h and 24 h after CA. Endovascular hypothermia offered a method to rapidly achieve the target temperature and provide stable target temperature management (TTM). Cardiac outcomes were improved and myocardial injuries were alleviated with endovascular hypothermia. Compared with NTG, endovascular hypothermia significantly increased mitochondrial activity and biogenesis by amplifying mitochondrial biogenesis factors' expressions, including PGC-1α, NRF-1, and NRF-2. In conclusions, endovascular hypothermia after CA alleviated myocardial and mitochondrial dysfunction, and was associated with increasing mitochondrial biogenesis.

Amplitude screening improves performance of AMSA method for predicting success of defibrillation in swine model.

PURPOSE: A novel amplitude screening method, termed Optimal Amplitude Spectrum Area (Opt-AMSA) with the aim of improving the performance of the Amplitude Spectrum Area (AMSA) method, was proposed to optimize the timing of defibrillation. We investigated the effects of the Opt-AMSA method on the prediction of successful defibrillation when compared with AMSA in a porcine model of ventricular fibrillation (VF). METHOD: 60 male domestic pigs were untreated in the first 10 min of VF, then received cardiopulmonary resuscitation (CPR) for 6 min. Values of Opt-AMSA and AMSA were calculated every minute before defibrillation. Linear regression was used to evaluate the correlation between Opt-AMSA and AMSA. Receiver Operating Characteristic (ROC) analysis was conducted for the two methods and to compare their predictive values. RESULTS: The values of both AMSA and Opt-AMSA gradually decreased over time during untreated VF in all animals. The values of both methods of defibrillation were slightly increased after the implementation of CPR in animals that were successfully resuscitated, while there were no significant changes in either method in those who ultimately failed to resuscitate. The significant positive correlation between Opt-AMSA and AMSA was shown by Pearson correlation analysis. ROC analysis showed that Opt-AMSA (AUC = 0.87) significantly improved the performance of AMSA (AUC = 0.77) to predict successful defibrillation (Z = 2.27, P < 0.05). CONCLUSION: Both the Opt-AMSA and AMSA methods showed high potential to predict the success of defibrillation. Moreover, the Opt-AMSA method improved the performance of the AMSA method, and may be a promising tool to optimize the timing of defibrillation.

CPR feedback/prompt device improves the quality of hands-only CPR performed in manikin by laypersons following the 2015 AHA guidelines.

PURPOSE: We investigated the effects of a cardiopulmonary resuscitation (CPR) feedback/prompt device on the quality of chest compression (CC) during hands-only CPR following the 2015 AHA guidelines. METHODS: A total of 124 laypersons were randomly assigned into three groups. The first (n=42) followed the 2010 guidelines, the second (n=42) followed the 2015 guidelines with no feedback/prompt device, the third (n=40) followed the 2015 guidelines with a feedback/prompt device (2015F). Participants underwent manual CPR training and took a written basic life support examination, then required to perform 2min of hands-only CPR monitored by a CPR feedback/prompt device. The quality of CPR was quantified as the percentage of correct CCs (mean CC depth and rate, complete recoil and chest compression fraction (CCF)) per 20s, as recorded by the CPR feedback/prompt device. RESULTS: Significantly higher correct ratios of CC, CC depth, and rate were achieved in the 2010 group in each minute vs the 2015 group. The greater mean CC depth and rate were observed in the 2015F group vs the 2015 group. The correct ratio of CC was significantly higher in the 2015F group vs the 2015 group. CCF was also significantly higher in the 2015F group vs the 2015 group in the last 20s of CPR. CONCLUSIONS: It is difficult for a large percentage of laypersons to achieve the targets of CC depth and rate following the 2015 AHA guidelines. CPR feedback/prompt devices significantly improve the quality of hands-only CPR performance by laypersons following the standards of the 2015 AHA guidelines.

Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model.

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

Outcome and prognostic factors in cervical cancer patients treated with surgery and concurrent chemoradiotherapy: a retrospective study.

BACKGROUND: The objective of this study is to analyze the treatment outcome and secondary reactions in 98 patients with stage I-III cervical carcinoma who underwent postoperative radiotherapy. METHODS: From 2006 to 2014, 98 patients with stage I-III cervical carcinoma were treated with postoperative radiotherapy. The major histological type, found in 92.86% of the patients (91 cases), was squamous cell carcinoma. Patients were staged according to the 2002 TNM guidelines. The postoperative radiotherapy methods included two-field irradiation (16 patients, 16.32%), four-field box irradiation (16 patients, 16.32%), and intensity-modulated radiotherapy (IMRT; 66 patients, 67.36%). The survival rates were represented using Kaplan-Meier curves, and prognosis analyses were performed using Cox multivariate analyses. RESULTS: The 5-year overall survival and progression-free survival rates were 82.0 and 76.0%, respectively. Only one patient (1.02%) developed a grade 3 acute radiation enteritis, while grade 3 and 4 myelosuppression was noted in 17 patients (17.35%) and one patient (1.02%), respectively. Multivariate analyses showed that anemia before radiotherapy and tumor size were predictors of the OS (P = 0.008, P = 0.045) rates. CONCLUSIONS: Postoperative radiotherapy for patients with risk factors of cervical cancer procured good efficacy levels with mild side effects. Anemia and tumor size were important OS predictors.

mRNA Analysis of Genes Encoded with Phytochelatin Synthase (PCS) in Rice Seedlings Exposed to Chromium: The Role of Phytochelatins in Cr Detoxification.

Transcriptional changes of genes encoded with phytochelatins synthase (PCS) was investigated in rice seedlings exposed to potassium chromate Cr(VI) or chromium nitrate Cr(III) using qRT-PCR. Our study demonstrates that both Cr variants initiated different responses of phytochelatin content and PCS activities in rice tissues. Six putative PCS genes were expressed differentially in response to both Cr species. Comparing gene expression between root/shoots, only LOC_Os05g34290.1 and LOC_Os06g01260.1 genes were expressed in similar patterns in Cr(VI) treatment, while none of them were expressed equally in Cr(III) treatments. Inconsistent expression of PCS genes in two Cr variants as well as in rice tissues were most likely related to its individual chemical properties and chemical speciation. Results presented here indicate that the role of phytochelatins in Cr detoxification between two Cr variants in rice was different and six putative PCS genes functioned differently in stimulating PCS activities and regulating phytochelatin formation.

Expression of HIF-1α and HIF-2α correlates to biological and clinical significance in papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to detect the expression of hypoxia-inducible factor (HIF)-1α and HIF-2α in papillary thyroid carcinoma (PTC) compared with normal thyroid tissues. METHODS: The mRNA levels and protein levels of HIF-1α and HIF-2α were detected by real-time PCR and Western blot separately in 30 pairs of PTCs and normal thyroid cases. The protein levels were also detected by immunohistochemistry (IHC) using 92 samples of PTC group and 46 normal samples as control group for analyzing the biological and clinical significance of the expression of HIF-1α/HIF-2α. RESULTS: Real-time PCR results showed the mRNA level of HIF-1α and HIF-2α were significantly higher in PTC than normal group (P<0.001). Also, significantly higher positive rates (73%/65%) of HIF-1α and HIF-2α were observed in PTC compared with the control group (27%/35%) by IHC (P<0.01); the consistent results were gotten with Western blot. Although we did not find a significant correlation between the expression of HIF-1α and HIF-2α with gender, age, calcification, or Hashimoto's disease in the present study (P>0.05), both of their expressions were correlated to lymph node metastasis (P<0.05), capsular invasion (P<0.05), and TNM stage (P<0.05). CONCLUSIONS: Overexpression of HIF-1α and HIF-2α are associated with the carcinogenesis of PTC, served as potential biomarkers of PTC.

MAPK pathway mediates epithelial-mesenchymal transition induced by paraquat in alveolar epithelial cells.

Epithelial-mesenchymal transition (EMT) is believed to be involved in lung fibrosis process induced by paraquat (PQ); however, the molecular mechanism of this process has not been clearly established. The present study investigated the potential involvement of EMT after PQ poisoning. The expressions of EMT markers, such as E-cadherin and α-smooth muscle actin (α-SMA), at multiple time points after exposure to different concentrations of PQ were evaluated by western blot analysis. Following PQ treatment, EMT induction was observed under microscopy. Related fibrosis genes, including Matrix metalloproteinase 2 (MMP-2), Matrix metalloproteinase 9 (MMP-9), collagens type I (COL I), and type III (COL III), were also evaluated by measuring their mRNA levels using RT-PCR analysis. Signaling pathways were analyzed using selective pharmacological inhibitors for MAPK. Cell migration ability was evaluated by scratch wound and Transwell assays. The data showed that PQ-induced epithelial RLE-6NT cells to develop mesenchymal cell characteristics, as indicated by a significant decrease in the epithelial marker E-cadherin and a significant increase in the extracellular matrix (ECM) marker α-smooth muscle actin in a dose and time-dependent manner. Moreover, PQ-treated RLE-6NT cells had an EMT-like phenotype with elevated expression of MMP-2, MMP-9, and COL I and COL III and enhanced migration ability. Signal pathway analysis revealed that PQ-induced EMT led to ERK-1 and Smad2 phosphorylation through activation of the MAPK pathway. The results of the current study indicate that PQ-induced pulmonary fibrosis occurs via EMT, which is mediated by the MAPK pathway. This implies that the MAPK pathway is a promising therapeutic target in alveolar epithelial cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1407-1414, 2016.

[Changes in expression of PYCARD gene and its transcript variant mRNA in peripheral blood mononuclear cells of patients with primary gout].

OBJECTIVE: To determine the expression level and role of PYCARD [PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase recruitment domain (CARD), PYCARD] gene and its transcript variant mRNA in peripheral blood mononuclear cells (PBMCs) of patients with primary gout (PG). METHODS: PYCARD gene and its transcript variant mRNA were measured using reverse transcription-polymerase chain reaction (RT-PCR) in PBMCs. The expression of PYCARD gene and PYCARD-1,-2 mRNA in PBMCs was compared between the patients with acute phase PG (APPG) (n=44), non-acute phase PG (NAPPG) (n= 51) and healthy controls (HC) (n=87). PYCARD and NF-kappaB (p105/p50) protein expressions were measured using Western blot in the PBMCs of participants in the PG and HC groups. Routine blood tests and blood uric acid test were undertaken in all participants. Differences in the indicators were examined among the three groups. Correlations between the expression of PYCARD gene and PYCARD-1,-2 mRNA and other indicators were analyzed. RESULTS: The expression level of PYCARD gene, PYCARD-1,-2 mRNA was significantly higher in the APPG and NAPPG group than in the HC group (P<0.01). The NAPPG group had significantly higher levels of PYCARD gene transcript variant 2x mRNA and 2y mRNA in the HC and APPG groups (P<0.05). The expression of PYCARD and NF-kappaB (p105/p50) protein was significantly higher in the PG group compared with the HC group [(4.900 +/- 1.324) vs. (3.975 +/- 0.210) and (0.263 +/- 0.106) vs. (0.127 +/- 0.008), respectively P<0.05]. The expression level of PYCARD-2 mRNA and granulocyte were positively correlated in the NAPPG group. CONCLUSION: Abnormal expression of PYCARD gene and its transcript variant and PYCARD protein in PG patients suggests that PYCARD gene and its transcript variant may play an important role in regulating the inflammatory response of PG patients.

Saikosaponin-D enhances radiosensitivity of hepatoma cells under hypoxic conditions by inhibiting hypoxia-inducible factor-1α.

BACKGROUND: Our previous study revealed that the combination of Saikosaponin-d ( SSd) and radiation is more effective in the treatment of liver cancer than the application of either of these monotherapeutic methods. However, the molecular mechanisms of the radiosensitizing effect of SSd on liver cancer remained ill defined. METHODS: Cells were treated with different interventions; afterward, cell viability, apoptosis, and cell survival of SMMC-7721 and HepG2 hepatoma cells were examined. Xenograft tumor models were established by subcutaneously injecting SMMC-7721 cells. The molecular mechanism was assessed by western blot. RESULTS: SSd dose-dependently increased radiosensitivity of hepatoma cells under hypoxic condition. The growth inhibitory effect of the combined treatment was correlated with cell apoptosis. Further mechanistic analysis indicated that SSd induced the upregulation of p53 and Bax as well as the downregulation of Bcl-2 by attenuating HIF-1α expression under hypoxic condition. These effects were enhanced when the HIF-1α inhibitor PX-478 was introduced. In vivo data also presented a more significant suppression of tumor xenograft growth from the combined therapy than from either of the monotherapeutic methods. CONCLUSIONS: Our study provides evidence for a radiosensitizing effect of SSd on hepatoma cells under hypoxic conditions by inhibiting HIF-1α expression. Thus, SSd can be used as a potential sensitizer in hepatoma radiotherapy. © 2014 S. Karger AG, Basel.