The Sensitization Differences of Pollen Allergen Components in Patients with Asthma and/or Rhinitis in Southern China.

INTRODUCTION: This study aim to analyzed the main pollen allergen components that cause allergic asthma and/or rhinitis and the cross-reactions between the allergen components. METHODS: Twenty one allergic rhinitis patients and 23 allergic asthma patients with pollen sensitization from the China Biological Information Repository of Respiratory Diseases were included. All the patients were detected serum pollen allergens components specific immunoglobulin E (sIgE) including Betula verrucosa (Bet v 1, Bet v 2, Bet v 4), Quercus alba (Pla a 1, Pla a 2), Ambrosia elatior (Amb a 1), Artemisia vulgaris (Art v 1, Art v 3, Art v 4), Bermuda grass (Cyn d 1, Cyn d 12), Phleum pratense (Phl p 5, Phl p 1, Phl p 4, Phl p 7, Phl p 12), and cross-reactive carbohydrate determinants. RESULTS: In patients with asthma, Phl p 4 had the highest positive rate (60.9%), followed by Phl p 1 (43.5%) and Pla a 2 (34.8%), while in patients with rhinitis, Amb a 1 had the highest positive rate (71.4%), followed by Phl p 4 (61.9%) and Pla a 2 (42.9%). Meanwhile, Phl p 1 (43.5%) in asthma patients was higher than that in rhinitis (4.7%, p = 0.03), while Amb a 1 (71.4%) in rhinitis patients was higher than that in asthma (26.1%, p = 0.03). Interestingly, optimal scale analysis show that the severity of both asthma and rhinitis is related to Bet v 4 (Cronbach's Alpha = 95.0%). CONCLUSIONS: In general, Phl p 4 is the main allergenic component in pollen sensitized asthma patients, while Amb a 1 is the main allergenic component in pollen sensitized rhinitis patients. Sensitization to Bet v 4 may lead to more severe symptoms, and this result may be applied in future clinical precise diagnosis.

Chemical Compositions of Scutellaria baicalensis Georgi. (Huangqin) Extracts and Their Effects on ACE2 Binding of SARS-CoV-2 Spike Protein, ACE2 Activity, and Free Radicals.

The water and ethanol extracts of huangqin, the roots of Scutellaria baicalensis Georgi. with potential antiviral properties and antioxidant activities, were investigated for their chemical profiles and their abilities to interfere with the interaction between SARS-CoV-2 spike protein and ACE2, inhibiting ACE2 activity and scavenging free radicals. A total of 76 compounds were tentatively identified from the extracts. The water extract showed a greater inhibition on the interaction between SARS-CoV-2 spike protein and ACE2, but less inhibition on ACE2 activity than that of the ethanol extract on a per botanical weight concentration basis. The total phenolic content was 65.27 mg gallic acid equivalent (GAE)/g dry botanical and the scavenging capacities against HO●, DPPH●, and ABTS●+ were 1369.39, 334.37, and 533.66 µmol trolox equivalent (TE)/g dry botanical for the water extract, respectively. These values were greater than those of the ethanol extract, with a TPC of 20.34 mg GAE/g, and 217.17, 10.93, and 50.21 µmol TE/g against HO●, DPPH●, and ABTS●+, respectively. The results suggested the potential use of huangqin as a functional food ingredient in preventing COVID-19.

Formation of Maillard Reaction Products in Aged Sorghum Vinegar during Ageing and Protective Effects of Pure Vinegar Melanoidin Against CCl4-Induced Rat Hepatic Damage.

Research background: The processing method generally affects the toxicity and biological activity of aged sorghum vinegar. This study investigates the changes in the intermediate Maillard reaction products of sorghum vinegar during ageing and the in vivo hepatoprotective effects of pure melanoidin obtained from it. Experimental approach: High-performance liquid chromatography (HPLC) and fluorescence spectrophotometry were utilized to quantify intermediate Maillard reaction products. The CCl4-induced liver damage in rats was used to evaluate the protective role of pure melanoidin in rat liver. Results and conclusions: Compared with the initial concentration, the 18-month ageing process caused a 1.2- to 3.3-fold increase in the concentrations of intermediate Maillard reaction products, i.e. 5-hydroxymethylfurfural (HMF), 5-methylfurfural (MF), methyglyoxal (MGO), glyoxal (GO) and advanced glycation end products (AGEs). The concentrations of HMF in the aged sorghum vinegar were 6.1-fold higher than the 450 µM limit standard for honey, implying the need for shortening the ageing of the vinegar in practice for safety concerns. Pure melanoidin (Mr>3.5 kDa) demonstrated significant protective effects against CCl4-induced rat liver damage, as evidenced by normalized serum biochemical parameters (transaminases and total bilirubin), suppressing hepatic lipid peroxidation and reactive oxygen species, as well as increasing glutathione amount and restoring antioxidant enzyme activities. Histopathological analysis revealed that melanoidin in vinegar reduced cell infiltration and vacuolar hepatocyte necrosis in rat liver. The findings demonstrated that a shortened ageing process should be considered in practice to ensure the safety of aged sorghum vinegar. Vinegar melanoidin is a potential alternative for the prevention of hepatic oxidative damage. Novelty and scientific contribution: This study demonstrates that the manufacturing process had a profound influence on the generation of vinegar intermediate Maillard reaction products. In particular, it revealed the in vivo hepatoprotective effect of pure melanoidin from aged sorghum vinegar, and provides insight into the in vivo biological activity of melanoidin.

MicroRNA-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis to prevent the epithelial-mesenchymal transition.

OBJECTIVE: Breast cancer is one of the most common malignant and highly heterogeneous tumors in women. MicroRNAs (miRNAs), such as miR-1246, play important roles in various types of malignant cancers, including triple-negative breast cancer (TNBC). However, the biological role of miR-1246 in TNBC has not yet been fully elucidated. In this study, we studied the role of miR-1246 in the occurrence and development of TNBC and its mechanism of action. METHODS: Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays were performed to observe the effects of miR-1246 on TNBC cell proliferation, migration, and invasion, respectively. The expression of epithelial-mesenchymal transition (EMT) markers was detected by western blotting. Dual luciferase reporter assays were performed to determine whether DYRK1A is a novel target of miR-1246. In addition, an immunoprecipitation experiment was performed to verify the binding of DYRK1A to PGRN. Rescue experiments were performed to determine whether DYRK1A is a novel target of miR-1246 and whether miR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis to prevent the epithelial-mesenchymal transition. RESULTS: Our results show that miR­1246 suppresses the proliferation, migration, and invasion of TNBC cells, DYRK1A is a novel target of miR-1246 and Importin-8 mediated miR-1246 nuclear translocation. MiR­1246 plays a suppressive role in the regulation of the EMT of TNBC cells by targeting DYRK1A. DYRK1A mediates the metastasis of triple-negative breast cancer via activation of the EMT. We identified PGRN as a novel DYRK1A-interacting protein. Overexpression of PGRN and DYRK1A promoted cell proliferation and migration of TNBC, but this effect was reversed by co-expression of miR-1246 mimics.DYRK1A and PGRN act together to regulate the occurrence and development of breast cancer through miR-1246. CONCLUSION: MiR-1246 suppresses the metastasis of breast cancer cells by targeting the DYRK1A/PGRN axis and preventing the epithelial-mesenchymal transition. The MiR-1246/DYRK1A/PGRN axis regulates TNBC progression, suggesting that MiR-1246 could be promising therapeutic targets for the treatment of TNBC.

CircPUM1 promotes hepatocellular carcinoma progression through the miR-1208/MAP3K2 axis.

Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT-related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up-regulating the expression of MAP3K2 via sponging miR-1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC.

Electrocatalytic Hydrogen Evolution by Cobalt Complexes with a Redox Non-Innocent Polypyridine Ligand.

Novel cobalt and zinc complexes with the tetradentate ppq (8-(1″,10″-phenanthrol-2″-yl)-2-(pyrid-2'-yl)quinoline) ligand have been synthesized and fully characterized. Electrochemical measurements have shown that the formal monovalent complex [Co(ppq)(PPh3)]+ (2) undergoes two stepwise ligand-based electroreductions in DMF, affording a [Co(ppq)DMF]-1 species. Theoretical calculations have described the electronic structure of [Co(ppq)DMF]-1 as a low-spin Co(II) center coupling with a triple-reduced ppq radical ligand. In the presence of triethylammonium as the proton donor, the cobalt complex efficiently drives electrocatalytic hydrogen evolution with a maximum turnover frequency of thousands per second. A mechanistic investigation proposes an EECC H2-evolving pathway, where the second ligand-based redox process (E), generating the [Co(ppq)DMF]-1 intermediate, initiates proton reduction, and the second proton transfer process (C) is the rate-determining step. This work provides a unique example for understanding the role of redox-active ligands in electrocatalytic H2 evolution by transition metal sites.

Morphologic analysis of alveolar bone in maxillary and mandibular incisors on sagittal views.

PURPOSE: The aim of this study was to analyze the morphologic features of alveolus in relatively healthy maxillary and mandibular incisors using cone-beam-computed tomography (CBCT). METHODS: CBCT images of 318 patients were retrospectively acquired. Alveolar bone in incisive area was divided into: type 1 (thick), type 2 (relatively thick with mono-plate concavity), type 3 (thin with double-plate concavities), and type 4 (vulnerably thin). Alveolus prevalence and widths were analyzed statistically relative to age, gender, and molar relationship. RESULTS: Prevalence of type 1 alveolus was 78.9% in maxillary central incisors, 15.1% in maxillary lateral incisors, 24.1% in mandibular central incisors, and 5.0% in mandibular lateral incisors. Type 2 alveolus was commonly observed in the maxillary lateral incisors (82.2%), mandibular central incisors (66.2%), and mandibular lateral incisors (87.9%). Prevalence of type 3 and 4 alveoli ranged from 0.0 to 9.4%. As for maxillary central incisors, type 1 was the widest both at the alveolar crest (7.77 ± 0.58 mm) and apical area (9.05 ± 1.86 mm), while type 3 had the lowest width at the apical region (4.08 ± 0.51 mm). Among maxillary central incisors, prevalence of type 1 tended to decrease with age. At all maxillary and mandibular incisor sites, alveolus widths were significantly thicker in males than in females. At maxillary lateral incisor and mandibular incisor sites, prevalence of alveolus type was significantly different among three molar relationships. CONCLUSION: A 4-type classification system was suggested for alveolus morphology in incisive region. Identification of alveolus type might aid in the corresponding treatment.

Immune-related long noncoding RNA signature for predicting survival and immune checkpoint blockade in hepatocellular carcinoma.

Long noncoding RNAs (lncRNAs) show multiple functions, including immune response. Recently, the immune-related lncRNAs have been reported in some cancers. We first investigated the immune-related lncRNA signature as a potential target in hepatocellular carcinoma (HCC) survival. The training set (n = 368) and the independent external validation cohort (n = 115) were used. Immune genes and lncRNAs coexpression were constructed to identify immune-related lncRNAs. Cox regression analyses were perfumed to establish the immune-related lncRNA signature. Regulatory roles of this signature on cancer pathways and the immunologic features were investigated. The correlation between immune checkpoint inhibitors and this signature was examined. In this study, the immune-related lncRNA signature was identified in HCC, which could stratify patients into high- and low-risk groups. This immune-related lncRNA signature was correlated with disease progression and worse survival and was an independent prognostic biomarker. Our immune-related lncRNA signature was still a powerful tool in predicting survival in each stratum of age, gender, and tumor stage. This signature mediated cell cycle, glycolysis, DNA repair, mammalian target of rapamycin signaling, and immunologic characteristics (i.e., natural killer cells vs. Th1 cells down, etc). This signature was associated with immune cell infiltration (i.e., macrophages M0, Tregs, CD4 memory T cells, and macrophages M1, etc.,) and immune checkpoint blockade (ICB) immunotherapy-related molecules (i.e., PD-L1, PD-L2, and IDO1). Our findings suggested that the immune-related lncRNA signature had an important value for survival prediction and may have the potential to measure the response to ICB immunotherapy. This signature may guide the selection of the immunotherapy for HCC.

Highly Active Manganese-Based CO2 Reduction Catalysts with Bulky NHC Ligands: A Mechanistic Study.

Because of the strong σ-donor and weak π-acceptor of the N-heterocyclic carbene (NHC), Mn-NHC complexes were found to be active for the reduction of CO2 to CO with high activity. However, some NHC-based manganese complexes showed low catalytic activity and required very negative potentials. We report herein that complex fac-[MnI(bis-MesNHC)(CO)3Br] [1; bis-MesNHC = 3,3-bis(2,4,6-trimethylphenyl)-(1,1'-diimidazolin-2,2'-diylidene)methane] could catalyze the electrochemical reduction of CO2 to CO with high activity (TOFmax = 3180 ± 6 s-1) at a less negative potential. Due to the introduction of the bulky Mes groups, a one-electron-reduced intermediate {[Mn0(bis-MesNHC)(CO)3]0 (2•)} was isolated as a packed "dimer" and crystallographically characterized. Stopped-flow Fourier-transform infrared spectroscopy was used to prove the direct reaction between doubly reduced intermediate fac-[Mn(bis-MesNHC)(CO)3]- and CO2; the tetracarbonyl Mn complex [Mn+(bis-MesNHC)(CO)4]+ ([2-CO]+) was captured, and its further reduction proposed as the rate-limiting step.

Value of serum tumor markers for predicting EGFR mutations in non-small cell lung cancer patients.

OBJECTIVES: We investigated whether serum tumor markers (STMs) represent a valuable noninvasive tool to predict epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. METHODS: A retrospective analysis was performed for 143 NSCLC patients at the Peking University International Hospital from December 2014 to December 2019. EGFR mutations in the tumor tissues were identified by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next generation sequencing (NGS). The relationships between EGFR mutation and several clinicopathological features were analyzed. RESULT: EGFR mutation were found more frequently in female (56.67%, P = 0.01), never-smokers (55.26%, P = 0.004), and those with lung adenocarcinoma (ADC) (52.17%, P < 0.001). The positive mutation rate for the EGFR gene were higher in the squamous cell carcinoma antigen (SCCA)group (≤1.5 ng/ml) and in the gastrin-releasing peptide precursor (preGRP) increased group (≥69.2 pg/ml), and this difference was statistically significant (P < 0.05). Univariate logistic regression analysis demonstrated that females (Odd ratio [OR]: 2.435, 95% confidence interval [CI]: 1.232, 4.813, P = 0.01) and never-smokers (OR = 0.370; CI = 0.186, 0.734; P = 0.004), lung adenocarcinoma patients (OR = 9.091; CI = 2.599, 21.800; P = 0.001), the SCC group (≤1.5 ng/ml) (OR = 0.331, CI = 0.120, 0.914; P = 0.033), and the preGRP group (≥69.2 pg/ml) (OR = 5.478, CI = 1.462, 20.528; P = 0.012) patients were risk factors for EGFR gene mutation. Multivariate logistic regression analysis demonstrated that lung ADC and proGRP elevation were independent risk factors for predicting EGFR gene positivity (P < 0.05). CONCLUSION: STMs are associated with mutant EGFR status and could be integrated with other clinical factors to facilitate the classification of EGFR mutation status among NSCLC patients.

Six genes as potential diagnosis and prognosis biomarkers for hepatocellular carcinoma through data mining.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the third of cancer mortality worldwide. Although the study of HCC has made great progress, the molecular mechanism and signal pathways of HCC are not yet clear. Therefore, it is necessary to investigate the early diagnosis and prognosis biomarkers for HCC. The aim of this study is to screen the relevant genes and study the association of gene expression with the survival status of HCC patients using bioinformatics approaches, in the hope of establishing marker genes for diagnosis and prognosis of HCC. The gene expression data and corresponding clinical information of HCC samples were downloaded from the The Cancer Genome Atlas database. We performed to study the relationship between gene expression and prognosis of HCC and screen significantly relevant genes associated with prognosis of HCC by analyzing survival and function enrichment of genes. In this study, we collected 421 samples with gene expression data, including 371 tumor samples and 50 normal samples. By using single factor Cox regression analysis, we screened 1,197 genes significantly associated with survival time in the modeling data containing 117 samples and also searched six genes as the best markers to predict living status of HCC patients. Besides, we established score system of survival risk of HCC. Our study recognized six genes (PGBD3, PGM5P3-AS1, RNF5, UTP11, BAG6, and KCND2) to be significantly associated with diagnosis and prognosis of HCC, providing novel targets for studying potential mechanism about the progression of HCC.

LTR-mediated retroposition as a mechanism of RNA-based duplication in metazoans.

In a broad range of taxa, genes can duplicate through an RNA intermediate in a process mediated by retrotransposons (retroposition). In mammals, L1 retrotransposons drive retroposition, but the elements responsible for retroposition in other animals have yet to be identified. Here, we examined young retrocopies from various animals that still retain the sequence features indicative of the underlying retroposition mechanism. In Drosophila melanogaster, we identified and de novo assembled 15 polymorphic retrocopies and found that all retroposed loci are chimeras of internal retrocopies flanked by discontinuous LTR retrotransposons. At the fusion points between the mRNAs and the LTR retrotransposons, we identified shared short similar sequences that suggest the involvement of microsimilarity-dependent template switches. By expanding our approach to mosquito, zebrafish, chicken, and mammals, we identified in all these species recently originated retrocopies with a similar chimeric structure and shared microsimilarities at the fusion points. We also identified several retrocopies that combine the sequences of two or more parental genes, demonstrating LTR-retroposition as a novel mechanism of exon shuffling. Finally, we found that LTR-mediated retrocopies are immediately cotranscribed with their flanking LTR retrotransposons. Transcriptional profiling coupled with sequence analyses revealed that the sense-strand transcription of the retrocopies often lead to the origination of in-frame proteins relative to the parental genes. Overall, our data show that LTR-mediated retroposition is highly conserved across a wide range of animal taxa; combined with previous work from plants and yeast, it represents an ancient and ongoing mechanism continuously shaping gene content evolution in eukaryotes.

Prolyl oligopeptidase regulates progesterone secretion via the ERK signaling pathway in murine luteal cells.

Prolyl oligopeptidase (POP), one of the most widely distributed serine endopeptidases, is highly expressed in the ovaries. However, the physiological role of POP in the ovaries is not clear. In this study, we investigated the significance of POP in the corpus luteum. Murine luteal cells were cultured in vitro and treated with a POP selective inhibitor, (2S)-1[[(2 S)-1-(1-oxo-4-phenylbutyl)-2-pyrrolidinyl carbonyl]-2-pyrrolidinecarbonitrile (KYP-2047). We found that KYP-2047 treatment decreased progesterone secretion. In contrast, POP overexpression increased progesterone secretion. Three essential steroidogenic enzymes, including p450 cholesterol side-chain cleavage enzyme (CYP11A), 3ß-hydroxysteroid dehydrogenase (3ß-HSD), and the steroidogenic acute regulatory protein (StAR), were regulated by POP. Further studies showed that POP overexpression increased ERK1/2 phosphorylation and increased the expression of steroidogenic factor 1 (SF1), while KYP-2047 treatment decreased ERK1/2 phosphorylation and SF1 expression. To clarify the role of ERK1/2 signaling in POP-regulated progesterone synthesis, U0126-EtOH, an inhibitor of the ERK signaling pathway, was used to treat luteal cells. We found that U0126-EtOH decreased progesterone production and the expression of steroidogenic enzymes and SF1. POP overexpression did not reverse the effects of U0126-EtOH. Overall, POP regulates progesterone secretion by stimulating the expression of CYP11A, 3ß-HSD, and StAR in luteal cells. ERK signaling and downstream SF1 expression contribute to this process.

Evaluation of Parotid Gland Function Before and After Endoscopy-Assisted Stone Removal.

PURPOSE: To quantify gland function before and after endoscopy-assisted lithectomy for patients with parotid stones and to analyze correlations among different evaluation modalities. MATERIALS AND METHODS: This study investigated 58 patients (27 men and 31 women) with a stone larger than 5 mm or multiple parotid stones who underwent successful endoscopy-assisted surgery at the authors' center from August 2007 through September 2017. Meticulous postoperative manipulations were administered routinely for 3 to 6 months to promote functional recovery of the affected gland. Gland function was evaluated preoperatively and 6 to 36 months (mean, 12 months) postoperatively by sialography, scintigraphy, and sialometry. Statistical analyses were conducted to quantify gland function recovery and to distinguish correlations among the 3 objective tests. RESULTS: Preoperative sialograms exhibited ductal ectasia at the stone site with ductal stenosis anterior to the stone (n = 53) or duct interruption at the stone site (n = 5). Postoperative sialograms of 45 patients without stones were categorized as approximately normal (type I; n = 17); showing ectasia or stenosis of the main duct without persistent contrast on the functional film (type II; n = 16); showing ectasia or stenosis of the main duct with mild contrast retention (type III; n = 6); or showing poor ductal shape with evident contrast retention (type IV; n = 6). Scintigraphy of 23 preoperative and 12 postoperative patients and sialometry of 24 preoperative and 12 postoperative patients indicated severe preoperative impairment and postoperative improvement of gland function. Postoperatively, although no relevant differences in saliva flow rate were found between the 2 sides, scintigraphy showed lower function of the affected gland compared with the control side. Statistical data showed positive correlations among the 3 methods. Sialography intuitively reflected the ductal shape, whereas sialometry and scintigraphy were more sensitive for evaluating gland function. CONCLUSION: For patients with parotid stones, minimally invasive endoscopic surgery and meticulous postoperative manipulations help preserve the glands and facilitate recovery of gland function. The 3 evaluating modalities have certain positive correlations.

Dietary sn-2 palmitic triacylglycerols reduced faecal lipids, calcium contents and altered lipid metabolism in Sprague-Dawley rats.

In this study, the impact of dietary sn-2 palmitic triacylglycerol (sn-2 PTAG) on faecal lipids, calcium excretion and lipid metabolic alternation was investigated in Sprague-Dawley (SD) rats fed with high-fat diet containing either palm olein (PO, sn-2 palmitic acid (PA) of 14.8%), sn-2 PTAG50 (sn-2 PA of 56.4%) or sn-2 PTAG70 (sn-2 PA of 72.4%), respectively. After 4-week feeding period, SD rats fed with sn-2 PTAGs showed reduced faecal soap fatty acids, neutral lipid and calcium excretion compared to those of PO-fed rats, whereas a significant difference was only observed for the sn-2 PTAG70-fed rats (p < .05). Moreover, dietary sn-2 PTAG70 also showed a significant effect on decreasing serum triacylglycerol (TAG) level, reducing perirenal adipocyte size and regulating lipid metabolism in small intestine and perirenal adipose tissue of SD rats. Significantly increased mRNA levels of genes involved in intestinal lipid anabolism as well as lipid catabolism were both observed in the sn-2 PTAG70-fed rats (p < .05). Meanwhile, dietary sn-2 PTAG70 also significantly up-regulated lipolysis, mitochondrial fatty acid oxidation and thermogenesis-related gene and protein levels in perirenal adipose tissue, which might be correlated with the reduced perirenal adipocyte size. Taken together, our findings indicated that sn-2 PTAG70 may have some beneficial effects on intestinal lipid utilisation and lipid metabolic activity for energy supply in visceral adipose tissue.

Fabrication and Characterization of Zein Composite Particles Coated by Caseinate-Pectin Electrostatic Complexes with Improved Structural Stability in Acidic Aqueous Environments.

Zein composite particles coated with caseinate-pectin electrostatic complexes (zein-caseinate-pectin particles) were fabricated using an electrostatic deposition and liquid-liquid dispersion method without heating treatment. Compared to zein particles coated only with caseinate, the acidic stability of zein-caseinate-pectin particles was greatly improved, and the particle aggregation was suppressed at pH 3-6, especially at pH values near the isoelectric point of caseinate (pH 4-5). Besides, desirable long-term storage stability and re-dispersibility were observed. Under different zein to curcumin (Cur) feeding ratios (10:1, 20:1, 30:1 and 40:1, w/w), the Cur-loaded zein-caseinate-pectin particles had a spherical shape with an average diameter ranging from 358.37 to 369.20 nm, a narrow size distribution (polydispersity index < 0.2) and a negative surface charge ranging from -18.87 to -19.53 mV. The relatively high encapsulation efficiencies of Cur (81.27% to 94.00%) and desirable re-dispersibility were also achieved. Fluorescence spectroscopy indicated that the encapsulated Cur interacted with carrier materials mainly through hydrophobic interactions. The in-vitro release profile showed a sustained release of Cur from zein-caseinate-pectin particles in acidic aqueous environment (pH 4) up to 24 h, without any burst effect. In addition, the encapsulation retained more ABTS•+ radical scavenging capacity of Cur during 4 weeks of storage. These results suggest that zein-caseinate-pectin particles may be used as a potential delivery system for lipophilic nutrients in acidic beverages.

Droxinostat sensitizes human colon cancer cells to apoptotic cell death via induction of oxidative stress.

Upregulation of histone acetylation plays a critical role in the dysregulation of transcription. It alters the structure of chromatin, which leads to the onset of cancer. Histone deacetylase inhibitors may therefore be a promising way to limit cancer progression. In this study, we examined the effects of droxinostat on the growth of HT-29 colon cancer cells. Our results show that droxinostat effectively inhibited cell growth and colony-forming ability by inducing cellular apoptosis and ROS production in HT-29 cells. Notably, the apoptotic inhibitor Z-VAD-FMK significantly decreased the levels of cellular apoptosis and the antioxidant γ-tocotrienol (GT3) significantly decreased ROS production induced by droxinostat treatment. Z-VAD-FMK and GT3 also partially reversed the negative growth effects of droxinstat on HT-29 cells. GT3 treatment decreased cellular apoptosis and increased colony-forming ability upon droxinostat administration. Z-VAD-FMK treatment also partially decreased droxinostat-induced ROS production. Our findings suggest that the effects of droxinostat on colon cancer cells are mediated by the induction of oxidative stress and apoptotic cell death.

ARID1A suppresses malignant transformation of human pancreatic cells via mediating senescence-associated miR-503/CDKN2A regulatory axis.

ARID1A as a subunit of SWI/SNF chromatin complexes is frequently mutated in human pancreatic cancer, however its exact role in pancreatic tumorigenesis remain unclear. In this study, we investigated the effects of ARID1A loss on human pancreatic epithelial cell lines HPNE, BxPC-3 with KRAS mutant (KRASG12D) expression. We found that ARID1A knockdown promoted cell proliferation and colony formation in cooperation with active mutant KRASG12D. Function assay revealed that ARID1A knockdown accelerated cell cycle progression, and repressed KRASG12D-induced cell senescence. Transcriptome analysis revealed ARID1A knockdown led to miR-503 upregulation. CDKN2A was identified as a target of miR-503, which contributes to cell senescence. Thus, our data suggests that ARID1A deficiency promote KRASG12D-driven pancreatic tumorigenesis through miR-503/CDKN2A-mediated senescence.

Reaction mechanism of hydrogen evolution catalysed by Co and Fe complexes containing a tetra-dentate phosphine ligand - a DFT study.

The reaction mechanism of the electro-catalytic proton reduction in neutral phosphate buffer enabled by mononuclear cobalt and iron complexes containing a tetra-dentate phosphine ligand (MP4N2, M = Fe, Co) has been elucidated by density functional calculations. The phosphate from the buffer was found to play a crucial role by coordinating to the metal and delivering a proton to the metal hydride in the H-H bond formation. For the more efficient cobalt catalyst, the starting species is a CoII complex with a hydrogen phosphate and a water molecule ligated at the two vacant coordination sites. Two sequential proton-coupled electron transfer reductions lead to the formation of a CoII-H intermediate with a dihydrogen phosphate ligand, and the reduction potentials for these two steps were calculated to be -0.58 V and -0.72 V, respectively. Subsequently, the H-H bond formation takes place via coupling of the CoII-H and the proton from the dihydrogen phosphate ligand. The total barrier was calculated to be 18.2 kcal mol-1 with an applied potential of -0.5 V, which can further decrease to only 11.2 kcal mol-1 with an applied potential of -0.8 V. When the phosphate is displaced by a water molecule, the total barrier for the dihydrogen formation increases by 7.3 kcal mol-1. For the iron catalyst, the overall mechanism is essentially the same; however, the first reduction (FeII/FeI, potential of -1.13 V) is likely the rate-limiting step. The calculated results are in good agreement with the experimental data, which showed an onset potential of -0.50 V for the cobalt complex and -1.03 V for the iron complex.

[Optimization of isolation and culture of Lin- Sca-1+ cardiac stem cells from newborn mice].

Cardiac stem cells (CSCs) transplantation has been recognized to be effective on the treatment of myocardial infarction (MI), but some techniques still need to be developed in the isolation and culture of CSCs, which is the key problem restricting the clinical application of CSCs. This study was focused on the isolation of Lin- (lineage-negative) Sca-1+ (stem cell antigen-1-positive) CSCs from newborn C57BL/6J mice (0-3 d) by mixed enzymatic-explant isolation in combination with immunomagnetic separation. The digesting time, digesting frequency, incubation temperature, stirring speed, centrifugation time and rotational speed were strictly controlled in the experiment. In order to increase the survival rate of CSCs, the medium changing time and manner were optimized in primary CSCs culture. The percentages of Sca-1+ cells in primary and passage cells were detected by flow cytometry and immunofluorescence staining. The results showed that: (1) the proportion of Lin- Sca-1+ cells within the collected cells could be as high as (85.03 ± 5.60)% after isolation and purification; (2) In vitro culture of Lin- Sca-1+ CSCs grew into spheres on the 5th day, and over the whole bottom of the dish on the 7th day. The growth curve showed that the cells were in logarithmic growth phase on the 3rd day; (3) Immunofluorescence staining data showed that the expression of Sca-1, the CSCs membrane-specific marker, was decreased after subculture, and flow cytometry data showed that the percentages of Sca-1+ cells were (71.82 ± 2.63)%, (58.38 ± 3.70)% and (46.19 ± 4.72)% in passage 1 (P1), P3, and P5 CSCs, respectively. The above results suggest that high purity of Lin- Sca-1+ CSCs can be obtained by enzymolysis combined with immunomagnetic separation method. Moreover, the CSCs culture system is stable. In our experiment, the Sca-1+ CSCs isolation and culture method has been successfully established, and it is simple, stable, effective and reliable. The method can provide a stable methodological basis for the treatment of MI by Lin- Sca-1+ CSCs transplantation.