Dipeptidyl Peptidase 4 Inhibition for Prophylaxis of Acute Graft-versus-Host Disease.

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4; also known as CD26), a transmembrane receptor expressed on T cells, has a costimulatory function in activating T cells. In a mouse model, down-regulation of CD26 prevented graft-versus-host disease (GVHD) but preserved graft-versus-tumor effects. Whether inhibition of DPP-4 with sitagliptin may prevent acute GVHD after allogeneic stem-cell transplantation is not known. METHODS: We conducted a two-stage, phase 2 clinical trial to test whether sitagliptin plus tacrolimus and sirolimus would reduce the incidence of grade II to IV acute GVHD from 30% to no more than 15% by day 100. Patients received myeloablative conditioning followed by mobilized peripheral-blood stem-cell transplants. Sitagliptin was given orally at a dose of 600 mg every 12 hours starting the day before transplantation until day 14 after transplantation. RESULTS: A total of 36 patients who could be evaluated, with a median age of 46 years (range, 20 to 59), received transplants from matched related or unrelated donors. Acute GVHD occurred in 2 of 36 patients by day 100; the incidence of grade II to IV GVHD was 5% (95% confidence interval [CI], 1 to 16), and the incidence of grade III or IV GVHD was 3% (95% CI, 0 to 12). Nonrelapse mortality was zero at 1 year. The 1-year cumulative incidences of relapse and chronic GVHD were 26% (95% CI, 13 to 41) and 37% (95% CI, 22 to 53), respectively. GVHD-free, relapse-free survival was 46% (95% CI, 29 to 62) at 1 year. Toxic effects were similar to those seen in patients undergoing allogeneic stem-cell transplantation. CONCLUSIONS: In this nonrandomized trial, sitagliptin in combination with tacrolimus and sirolimus resulted in a low incidence of grade II to IV acute GVHD by day 100 after myeloablative allogeneic hematopoietic stem-cell transplantation. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02683525.).

Effect of PI3K/AKT/mTOR signaling pathway-based clustered nursing care combined with papaverine injection on vascular inflammation and vascular crisis after replantation of severed fingers.

This research aimed to investigate the effect of PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B)/mTOR (mammalian target protein of rapamycin) signaling pathway-based clustering care combined with papaverine injection on vascular inflammation and vascular crisis after finger amputation and replantation. 100 patients admitted in General Hospital of Ningxia Medical University from April 2022 to December 2022 for replantation of severed fingers were selected and divided into a control group (n = 50) and an observation group (n = 50) using the randomized grouping principle. The control group received a papaverine injection and general nursing care, the observation group received a papaverine injection and clustered care. The pain score; constipation incidence; replantation finger survival rate; physician, nurse, and patient satisfaction; serum inflammatory factors; vascular crisis parameters; and occurrence of adverse reactions were compared between the two patient groups. Enzyme-linked immunosorbent assay was performed to detect PI3K, AKT, and mTOR protein concentrations in the venous blood of the two groups, and statistical analysis of the data was performed. On postoperative day 7, the pain score and incidence of constipation in the observation group were lower than those in the control group (P < 0.05); the survival rate of reimplanted fingers in the observation group was 88.00%, which was higher than that in the control group 80.00% (P < 0.05); the satisfaction of doctors, nurses, and patients in the observation group was higher than that in the control group; the concentrations of interleukin-1 (IL-1), tumor necrosis factor (TNF-α), blood flow resistance index (RI), and arterial pulsatility index (PI) in the observation group were lower than those in the control group, while the concentration of interleukin-10 (IL-10), vascular diameter, and Vm (mean blood flow velocity) were higher in the observation group than those in the control group; the differences were statistically significant (P < 0.05). The difference in the incidence of adverse reactions between the two groups was not statistically significant (P > 0.05). The concentrations of PI3K, AKT, and mTOR proteins in the observation group were higher than those in the control group (P < 0.05). The concentrations of PI3K, AKT, and mTOR proteins in the observation group were higher than those in the control group (P < 0.05). Overall, these findings suggest that clustered care combined with papaverine injection reduces vascular inflammatory symptoms and vascular crisis in the treatment of severed finger replantation through the PI3K/AKT/mTOR signaling pathway.

Composition and evolutionary characterization of the gut microbiota in pigs.

The intestinal microbiota plays significant role in the physiology and functioning of host organisms. However, there is limited knowledge of the composition and evolution of microbiota-host relationships from wild ancestors to modern domesticated species. In this study, the 16S rRNA gene V3-V4 in the intestinal contents of different pig breeds was analyzed and was compared using high-throughput sequencing. This identified 18 323 amplicon sequence variants, of which the Firmicutes and Actinobacteria phyla and Bifidobacterium and Allobaculum genera were most prevalent in wild pigs (WP). In contrast, Proteobacteria and Firmicutes predominated in Chinese Shanxi Black pigs (CSB), while Firmicutes were the most prevalent phylum in Large White pigs (LW) and Iberian pigs (IB), followed by Bacteroidetes in IB and Proteobacteria in LW. At the genus level, Shigella and Lactobacillus were most prevalent in CSB and LW, while Actinobacillus and Sarcina predominated in IB. Differential gene expression together with phylogenetic and functional analyses indicated significant differences in the relative abundance of microbial taxa between different pig breeds. Although many microbial taxa were common to both wild and domestic pigs, significant diversification was observed in bacterial genes that potentially influence host phenotypic traits. Overall, these findings suggested that both the composition and functions of the microbiota were closely associated with domestication and the evolutionary changes in the host. The members of the microbial communities were vertically transmitted in pigs, with evidence of co-evolution of both the hosts and their intestinal microbial communities. These results enhance our understanding and appreciation of the complex interactions between intestinal microbes and hosts and highlight the importance of applying this knowledge in agricultural and microbiological research.

Buckley-James boosting model based on extreme learning machine and random survival forests.

Buckley-James (BJ) model is a typical semiparametric accelerated failure time model, which is closely related to the ordinary least squares method and easy to be constructed. However, traditional BJ model built on linearity assumption only captures simple linear relationships, while it has difficulty in processing nonlinear problems. To overcome this difficulty, in this paper, we develop a novel regression model for right-censored survival data within the learning framework of BJ model, basing on random survival forests (RSF), extreme learning machine (ELM), and L2 boosting algorithm. The proposed method, referred to as ELM-based BJ boosting model, employs RSF for covariates imputation first, then develops a new ensemble of ELMs-ELM-based boosting algorithm for regression by ensemble scheme of L2 boosting, and finally, uses the output function of the proposed ELM-based boosting model to replace the linear combination of covariates in BJ model. Due to fitting the logarithm of survival time with covariates by the nonparametric ELM-based boosting method instead of the least square method, the ELM-based BJ boosting model can capture both linear covariate effects and nonlinear covariate effects. In both simulation studies and real data applications, in terms of concordance index and integrated Brier sore, the proposed ELM-based BJ boosting model can outperform traditional BJ model, two kinds of BJ boosting models proposed by Wang et al., RSF, and Cox proportional hazards model.

Rapid Ozone Decomposition over Water-activated Monolithic MoO3 /Graphdiyne Nanowalls under High Humidity.

Catalytic ozone (O3 ) decomposition at high relative humidity (RH) remains a great challenge due to the catalysts poison and deactivation under high humidity. Here, we firstly elaborate the role of water activation and the corresponding mechanism of the promoted O3 decomposition over the three-dimensional monolithic molybdenum oxide/graphdiyne (MoO3 /GDY) catalyst. The O3 decomposition over MoO3 /GDY reaches up to 100 % under high humid condition (75 % RH) at room temperature, which is 4.0 times as high as that of dry conditions, significantly surpasses other carbon-based MoO3 materials(≤7.1 %). The sp-hybridized carbon in GDY donates electrons to MoO3 along the C-O-Mo bond, facilitating water activation to form hydroxyl species. As a result, hydroxyl species dissociated from water act as new active sites, promoting the adsorption of O3 and the generation of new intermediate species (hydroxyl ⋅OH and superoxo ⋅O2 - ), which significantly lowers the energy barriers of O3 decomposition (0.57 eV lower than dry conditions).

Circ_0006948 Contributes to Cell Growth, Migration, Invasion and Epithelial-Mesenchymal Transition in Esophageal Carcinoma.

BACKGROUND: Circular RNAs (circRNAs) can act as promoters or inhibitors in cancer progression. Has_circ_0006948 (circ_0006948) was reported to aggravate the malignant behaviors of esophageal carcinoma (EC). AIMS: This study focused on investigating the molecular mechanism of circ_0006948 in EC progression. METHODS: The quantitative real-time polymerase chain reaction was performed to detect the expression of circ_0006948, microRNA-4262 (miR-4262) and fibronectin type III domain containing 3B (FNDC3B). Cell growth analysis was conducted by Cell Counting Kit-8 and colony formation assays. Cell migration and invasion were assessed by transwell assay. Epithelial-mesenchymal transition (EMT)-associated proteins and FNDC3B protein expression were assayed using western blot. Dual-luciferase reporter and RNA pull-down assays were performed to validate the target combination. Xenograft tumor assay was used for investigating the role of circ_0006948 in vivo. RESULTS: Circ_0006948 was upregulated in EC tissues and cells. Downregulating the expression of circ_0006948 or FNDC3B repressed cell growth, migration, invasion and EMT in EC cells. Target analysis indicated that miR-4262 was a target for circ_0006948 and FNDC3B was a downstream gene for miR-4262. Moreover, circ_0006948 could affect the expression of FNDC3B via sponging miR-4262. The effects of si-circ_0006948#1 on EC cells were partly restored by miR-4262 inhibition or FNDC3B overexpression. In addition, circ_0006948 also facilitated EC tumorigenesis in vivo by targeting the miR-4262/FNDC3B axis. CONCLUSION: Taken together, circ_0006948 functioned as an oncogenic factor in EC by the miR-4262-mediated FNDC3B expression regulation.

Simultaneous quantification of hepatitis A virus and norovirus genogroup I and II by triplex droplet digital PCR.

The representative enteric viruses responsible for global foodborne outbreaks that have become an essential concern for health authorities are Norovirus (NoV) and Hepatitis A virus (HAV). Droplet digital PCR (ddPCR) has recently emerged as an alternative platform for virus quantification due to its high precision, ultra-sensitivity, and lack of a standard curve need. Using a ratio-based probe-mixing strategy, we established a triplex ddPCR method to detect norovirus genogroup I (GI), genogroup II (GII), and HAV in food, drinking water, and faecal samples. The probe concentration, annealing temperature, and annealing/extension time were all tuned in the PCR amplification program. The detection limit for NoV GI, NoV GII, and HAV was 7.5, 5.0, and 5.0 copies/reaction, respectively. Furthermore, the suggested approach was validated on 114 samples, demonstrating greater sensitivity, accuracy, and anti-interference performance features than RT-qPCR.

Knockdown of circ_0011946 targets miR-216a-5p/BCL2L2 axis to regulate proliferation, migration, invasion and apoptosis of oral squamous cell carcinoma cells.

BACKGROUND: Circular RNAs (circRNAs) are implicated in the development of oral squamous cell carcinoma (OSCC). The aim of current research is to elucidate the role and mechanism of circ_0011946 in the functional behaviors of OSCC cells. METHODS: Circ_0011946, microRNA (miR)-216a-5p, B cell lymphoma-2-like 2 protein (BCL2L2) abundances were exposed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation, migration, invasion and apoptosis were detected by MTT, colony formation assay, transwell, wound-healing and flow cytometry assays, respectively. Target correlation was tested by dual-luciferase reporter and RNA pull-down assays. An in vivo xenograft experiment was employed to investigate the function of circ_0011946 on tumor growth in vivo. RESULTS: Circ_0011946 and BCL2L2 levels were increased, while miR-216a-5p level was decreased in OSCC tissues and cells. Circ_0011946 knockdown impeded proliferation, migration, and invasion, but promoted apoptosis in OSCC cells. Circ_0011946 functioned as a sponge for miR-216a-5p, and BCL2L2 was targeted by miR-216a-5p. Besides, miR-216a-5p or BCL2L2 knockdown partly attenuated the inhibitory influences of circ_0011946 silence or miR-216a-5p overexpression on OSCC cell progression. Furthermore, circ_0011946 post-transcriptionally regulated BCL2L2 through sponging miR-216a-5p. Moreover, circ_0011946 knockdown constrained OSCC tumor growth in vivo. CONCLUSION: Circ_0011946 silence repressed OSCC cell proliferation, migration, and invasion, but promoted apoptosis through the regulation of the miR-216a-5p/BCL2L2 axis.

Overweight and Obesity as Independent Factors for Increased Risk of Hepatocellular Cancer-Related Mortality: A Meta-Analysis.

Obesity is related to the amplified risk of developing hepatocellular cancer, but its outcome on hepatocellular cancer-related mortality remains uncertain. Hence, the present study aimed to perform a meta-analysis study to evaluate the relationship between weight and hepatocellular cancer-related deaths. Through a systematic literature search up to December 2019, 7 observational studies with 2,349,834 subjects, 4834 hepatocellular cancer-related deaths were identified reporting relationships between body mass index (BMI), and hepatocellular cancer-related mortality. Odd ratio (OR) with 95% confidence intervals (CIs) was calculated comparing obese, BML > 30kg/m2, and overweight, BMI, 25-29.9 kg/m2 to subjects with normal BMI using the dichotomous method with a random-effect model. In obese subjects, males (OR, 1.84; 95% CI, 1.25-2.70) and females (OR, 1.26; 95% CI, 1.11-1.44), had higher hepatocellular cancer-related mortality compared to normal BMI subjects. However, overweight males (OR, 1.12; 95% CI, 0.98-1.28) and overweight females (OR, 1.06; 95% CI, 0.95-1.18), did not have such risk with moderate heterogeneity. The extent of increased mortality was higher in obese males compared to obese females. The impact of obesity on hepatocellular cancer-related mortality was observed in all populations with less extant in the black population. Based on this meta-analysis, obesity may have an independent relationship with up to the 1.84-fold risk of hepatocellular cancer-related mortality. This relationship was more pronounced in males than in females. Key teaching pointsBeing overweight is related to the amplified risk of developing hepatocellular cancer.Obesity's affect on hepatocellular cancer-related mortality remains uncertain.Based on this meta-analysis, obesity may have an independent relationship with up to the 1.84-fold risk of hepatocellular cancer-related mortality.This relationship was more pronounced in males than in females.

Prevalence of Antibiotic Resistance Genes, Heavy Metal Resistance Genes and the Class 1 Integron Gene in Well Water and Tap Water Samples from Four Cities in Henan Province, China.

The presence of multi-resistance to both antibiotics and heavy metals in drinking water poses a significant risk to human health. Herein, we utilized qPCR to assess patterns of antibiotic resistance genes (ARGs), heavy metal resistance genes (HMRGs), and class 1 integron (intI1) gene expression levels in well and tap water samples from four cities in Henan Province, China. The relative abundance of most index values was higher in well water relative to tap water, or was highest in Shangqiu City and lowest in Puyang City on average. The expression of ARG was closely correlated with that of intI1 and HMRG in both well and tap water. Overall, our data highlighted the health threat posed by ARGs in the drinking water supply and underscore the potential for the transfer of these genes between bacteria with the aid of intI1 under selective pressure associated with human activity and heavy metal stress.

A CASPR1-ATP1B3 protein interaction modulates plasma membrane localization of Na+/K+-ATPase in brain microvascular endothelial cells.

Contactin-associated protein 1 (CASPR1 or CNTNAP1) was recently reported to be expressed in brain microvascular endothelial cells (BMECs), the major component of the blood-brain barrier. To investigate CASPR1's physiological role in BMECs, here we used CASPR1 as a bait in a yeast two-hybrid screen to identify CASPR1-interacting proteins and identified the ß3 subunit of Na+/K+-ATPase (ATP1B3) as a CASPR1-binding protein. Using recombinant and purified CASPR1, RNAi, GST-pulldown, immunofluorescence, immunoprecipitation, and Na+/K+-ATPase activity assays, we found that ATP1B3's core proteins, but not its glycosylated forms, interact with CASPR1, which was primarily located in the endoplasmic reticulum of BMECs. CASPR1 knockdown reduced ATP1B3 glycosylation and prevented its plasma membrane localization, phenotypes that were reversed by expression of full-length CASPR1. We also found that the CASPR1 knockdown reduces the plasma membrane distribution of the α1 subunit of Na+/K+-ATPase, which is the major component assembled with ATP1B3 in the complete Na+/K+-ATPase complex. The binding of CASPR1 with ATP1B3, but not the α1 subunit, indicated that CASPR1 binds with ATP1B3 to facilitate the assembly of Na+/K+-ATPase. Furthermore, the activity of Na+/K+-ATPase was reduced in CASPR1-silenced BMECs. Interestingly, shRNA-mediated CASPR1 silencing reduced glutamate efflux through the BMECs. These results demonstrate that CASPR1 binds with ATP1B3 and thereby contributes to the regulation of Na+/K+-ATPase maturation and trafficking to the plasma membrane in BMECs. We conclude that CASPR1-mediated regulation of Na+/K+-ATPase activity is important for glutamate transport across the blood-brain barrier.

Rapid detection of norovirus genogroup II in clinical and environmental samples using recombinase polymerase amplification.

Norovirus is the leading cause of acute gastroenteritis all over the world, and the most genotype that causes its epidemic is norovirus genogroup II (NoVs GII). Rapid detection of NoVs is important because it can facilitate timely diagnosis. In this study, we designed universal specific primers and an Exo probe to hybridize to all genetic clusters of NoVs GII based on the conserved region at the ORF1-ORF2 junction of the genome. For the first time, we established a rapid and reliable reverse transcription recombinase polymerase amplification (RT-RPA) method for the detection of NoVs GII within 20 min. This method can specifically amplify NoVs GII, and the detection limit was as low as 1.66 × 102 copies/µL. The method was validated in terms of LOD, accuracy, and specificity. We tested 55 real samples including foods, water, and feces. The results showed a sensitivity of 96% and specificity of 100% to NoVs GII. The whole procedure can be operated by a mobile suitcase laboratory, which is useful for resource-limited diagnostic laboratories. This novel real-time RT-RPA assay is an accurate tool for point-of-care testing of NoVs, providing practical support for norovirus-caused disease diagnosis and prevention.

Novel Poly(ADP-ribose) Polymerase-1 Inhibitor DDHCB Inhibits Proliferation of BRCA Mutant Breast Cancer Cell In Vitro and In Vivo through a Synthetic Lethal Mechanism.

Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are drugs that are effectively used to treat breast cancer. We synthesized a novel bromophenol derivative ethyl (E)-4-(2-(2,3-dibromo-4,5-dimethoxybenzylidene)hydrazine-1-carbothioamido)benzoate (DDHCB) as a novel PARP-1 inhibitor. Our study found that DDHCB could inhibit PARP-1 activity with an IC50 value of 58.3 nM. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide (MTT) assay indicated that DDHCB could selectively inhibit proliferation of BRCA mutant cells and demonstrate the ability of synthetic lethality. DDHCB could also induce DNA double-strand breaks with the ability to increase the foci quantitation of γ-H2AX. Moreover, DDHCB could increase PARP-1-DNA trapping and inhibit PAR formation in HCC-1937 cells. Further investigation showed that DDHCB induced apoptosis and G2/M cycle arrest. Finally, we found that DDHCB inhibited the growth of HCC-1937 xenografts with low toxicity. In vivo mechanisms showed that the level of γ-H2AX was increased in the DDHCB-treated tumors, indicating the PARP-1 inhibition ability of DDHCB in vivo. Our study results indicated that the future development of DDHCB for the treatment of breast cancer is promising.

Staphylococcus argenteus isolated from retail foods in China: Incidence, antibiotic resistance, biofilm formation and toxin gene profile.

Staphylococcus argenteus is a novel species of coagulase-positive staphylococci which was separated from Staphylococcus aureus in 2014. It can threaten human health like S. aureus but can not identify with conventional biochemical or other phenotypic testing. From 2011 to 2016, 1581 S. aureus strains were isolated from 4300 samples from retail foods covering most provincial capitals in China. According to multilocus sequence typing (MLST) and PCR confirmation, 7.2% of isolates (114/1581) were confirmed as S. argenteus. The pathogen was distributed in 22 of 39 sampled cities and all food types. Interestingly, most S. argenteus positive samples were collected from coastal cities in South China. MLST detected 8 different sequence types (STs), including five new STs. CC2250 was the predominant lineage of S. argenteus, followed by CC1223. To further characterize the isolates, their antibiotic resistance, virulence genes, biofilm formation and biofilm-related genes were examined. The pvl gene was not detected in S. argenteus, and only 1 isolate (0.9%) was positive for the tsst-1 gene. For 18 enterotoxin genes, 16.7% (19/114) of isolates harboured more than three genes, whereas 70.2% (80/114) of isolates had none of the investigated genes. Penicillin and ampicillin were the major antibiotics to which the S. argenteus isolates were resistant, followed by tetracycline, kanamycin and fusidic acid. A total of 94.7% of isolates had the ability to produce biofilms and all isolates harboured icaA, fnbA, and fib genes. Other biofilm-related genes, such as eno, clfB, fnbB, and icaC, were also found in 99.1%, 92.1%, 88.6%, and 74.6% of isolates, respectively. This study is the first systematic investigation of the prevalence of S. argenteus in retail foods in China and shows their ubiquity in food. We also provide comprehensive surveillance of the incidence of S. argenteus in retail foods and information to enable more accurate and effective treatment of infections of this new species.

Comparison Between the Gut Microbiota in Different Gastrointestinal Segments of Large-Tailed Han and Small-Tailed Han Sheep Breeds with High-Throughput Sequencing.

Commensal microorganisms are essential to the normal development and function of many aspects of animal biology. However, the dynamic shift patterns of the microbiota of different gut segments in sheep and the correlation between fat type large-tailed phenotype and microbiota remain poorly unknown. This study therefore sought to assess the composition and distribution of the intestinal microbiome, and compared the difference of gut microbiota from different gastrointestinal segments within breeds and same intestinal sections between breeds. For these analyses, 16S rRNA V4 regions from 4 gut sections prepared from each of six individuals (3 from each breed) were sequenced to detect the microbiome composition in these samples. These analyses revealed the presence of 51,173 operational taxonomic units distributed across 24 phyla and 420 genera in these samples, with Firmicutes and Bacteroidetes being the most prevalent phyla of microbes present in these samples. Moreover, the bacterial composition showed distinct microbial communities in different gastrointestinal segments within breed, but showed similar and relative fixed bacterial abundance in the same intestinal segments from individuals of different breeds. We also found that only a few bacterial species (Lachnospiraceae, Akkermansia) were needed to distinguish between Small-tailed Han sheep (STH) and Large-tailed Han sheep (LTH) and their metabolic process maybe influence the fat type large-tailed phenotype formation in sheep. The functional profile analysis revealed that the environment information processing, genetic information processing, and metabolic pathways were enriched in all samples. The main functional roles of the gut microbiota were amino acid metabolism, replication and repair, carbohydrate metabolism, and membrane transport. Finally, our findings suggested that distinguished gut species between STH and LTH have relative fixed and the potential correlation is existing between the intestinal microorganisms and the large-tailed phenotype trait formation of sheep, which may offer clues for further investigation to detect the roles of intestinal microbiota in the metabolism and fat deposition in the tail of sheep.

Quercetin attenuates oxidative stress-induced apoptosis via SIRT1/AMPK-mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model.

Apoptosis of chondrocytes are the main initiator of osteoarthritis (OA) and can be explained by oxidative stress and endoplasmic reticulum (ER) stress, thus the pharmacological interventions aimed at inhibiting of these pathways may be a promising approach for the management of OA. Quercetin is a member of the flavonoid family and has antioxidant and anti-inflammatory properties in degenerative diseases. However, its effects and potential mechanisms on the pathological process of OA are not very clear. The present study aimed to investigate the protective effects of quercetin on OA and the underlying mechanisms. The tert-butyl hydroperoxide (TBHP)-stimulated rat chondrocytes and destabilization of the medial meniscus OA rat model was used to explore the protective effects of quercetin. Our results showed that quercetin treatment can attenuate oxidative stress, ER stress, and associated apoptosis. Moreover, quercetin inhibited ER stress through activating the sirtuin1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) signaling pathway. The protective effects of quercetin were also observed in OA rat model which is evidenced by abolished cartilage degeneration and decreased chondrocytes apoptosis in the knee joints. Our results suggested that quercetin is a promising treatment for OA.

Effect and mechanism of lentivirus-mediated silencing of TPX2 gene on proliferation and apoptosis of human hepatoma cells.

This study aimed to investigate the role and mechanism of action of targeting protein for Xklp2 (TPX2) in liver cancer, we compared TPX messenger RNA (mRNA) expression in liver cancer tissue samples and adjacent normal liver tissue samples as well as in human liver cancer cell lines and nonmalignant cell line by quantitative reverse transcription polymerase chain reaction (qRT-PCR). TPX2 gene was silenced in HepG2 cells by transfection with the lentiviral vector expressing TPX2-targeting short hairpin RNA (shRNA), and the knockdown efficiency was evaluated by RT-qPCR. Cell proliferation, apoptosis as well as protein level of c-Myc, cyclin D1, caspase-3, phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß), and ß-catenin in HepG2 cells were evaluated before and after the TPX2 knockdown. Wnt/ß-catenin signaling pathway was inhibited by treatment with 20 µM of XAV-939 or activated by treatment with 20 mM of LiCl. We found that TPX2 mRNA level was significantly increased in liver cancer tissue samples and cell lines comparing to noncancerous counterparts (P < 0.05). TPX2 knockdown significantly reduces TPX2 expression (P < 0.01), cell proliferation (P < 0.05), protein level of c-Myc and cyclin D1 (P < 0.01), activation of Wnt/ß-catenin signaling in HepG2 cells (P < 0.01) while increasing cell apoptosis (P < 0.01). Treatment with XAV-939 significantly reduced HepG2 cell proliferation (P < 0.05) while increasing cell apoptosis (P < 0.01). Treatment with LiCl significantly attenuated the antiproliferative and apoptosis-promoting effect of TPX2 knockdown on HepG2 cells (P < 0.05). Lentivirus-mediated silencing of TPX2 gene could inhibit proliferation and induce apoptosis in hepatoma cells by inhibiting Wnt signaling pathway and regulating cyclin and apoptosis-related proteins.

Anticonvulsant and Neuroprotective Effects of Paeonol in Epileptic Rats.

Paeonol is the main active compound in the root bark extract of the peony tree, and it has antioxidative and anti-inflammatory effects. Recent studies have reported the neuroprotective effects of paeonol including its capacity in improving impaired memory. However, the effect of paeonol on epilepsy is yet to be demystified. We aimed to investigate the therapeutic effect of paeonol in epilepsy and its relationship with oxidative stress damage and neuronal loss in the rat brain to reveal the underlying mechanisms of epileptic seizures. A rat model for chronic epilepsy was established, and the seizure scores of the rats in different groups were recorded. The seizure duration and the seizure onset latency were used to evaluate the anticonvulsant effects of paeonol. Terminal deoxynucleotidyl transferase dUTP nick end-labeling staining, Nissl staining and H/E staining were used to evaluate the effects of paeonol on neuronal loss and apoptosis in epileptic rats. The colorimetric assessment of malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, catalase activity and total antioxidant capacity of paeonol were used in assessing paeonol's effect on oxidative stress in epileptic rats. Evaluation of Caspase-3 mRNA and protein expression levels were determined using western blot and quantitative real-time (RT-q)PCR. In this study, we found that paeonol reduced the seizure scores of epileptic rats and attenuated the duration and onset latency of seizures. Paeonol can also increase the activities of total antioxidant capacity, SOD and catalase activity and reduce MDA content as well. This suggests that paeonol can improve the level of oxidative stress in rats. More significantly, paeonol can improve neuronal loss and apoptosis in epileptic rats. These results indicate that paeonol has anticonvulsant and neuroprotective effects in epileptic rats. This effect may be caused by reducing oxidative stress.

Comparison of efficacy and safety of ilaprazole and esomeprazole both in initial treatment regimen and retreatment regimen of Helicobacter pylori infection in chronic gastritis.

The aim of this study was to compare the efficacy and safety of ilaprazole and esomeprazole both in initial treatment regimen and retreatment regimen of H. pylori infection in chronic gastritis and to explore risk factors for eradication failure. A total of 330 patients with chronic gastritis who were confirmed of H. pylori infection were enrolled in this study. 290 of them were initially treated patients and the 40 remained were patients with retreatment. Eradication assessment was performed at least four weeks after the completion of eradication therapy. Results showed that the eradication rates of the ilaprazole group and esomeprazole group were 91.4 % and 88.4 % for per-protocol (PP) analysis (p=0.41) and 89.0 % and 86.2 % for intention-to-treat (ITT) analysis (p=0.48) in initially treated patients. Meanwhile, they were 75.0 % and 72.2 % for PP analysis (p=0.85) and 75.0 % and 70.0 % for ITT analysis (p=0.72) in patients with retreatment. The differences were not statistically significant. There was also no significant difference in safety between the two drugs. A multiple logistic regression analysis showed that demographic factors such as age, gender, alcohol, smoking, coronary heart disease (CHD), hypertension (HTN) and diabetes mellitus (DM) did not affect eradication rates. However, patients with higher DOB values and patients with atrophic gastritis had significantly lower eradication rates than patients with lower DOB values and with non-atrophic gastritis whether the proton pump inhibitor (PPI) in eradication regimens was ilaprazole or esomeprazole. In conclusion, our findings suggest that the efficacy and safety of ilaprazole and esomeprazole were not significantly different both in initial treatment regimen and retreatment regimen of H. pylori infection in chronic gastritis and DOB values and type of chronic gastritis were to be independent risk factors for eradication failure. In addition, we discovered that a new quadruple regimen containing furazolidone and minocycline which achieved good efficacy and safety can be a promising option for retreatment of H. pylori infection.

The relationship of interpersonal sensitivity and depression among patients with chronic atrophic gastritis: The mediating role of coping styles.

AIMS AND OBJECTIVES: To investigate the prevalence of depression and the relationship among interpersonal sensitivity, coping styles and depression in patients with chronic atrophic gastritis and explore the mediating role of coping styles between interpersonal sensitivity and depression. METHODS: A cross-sectional survey of 101 patients diagnosed with chronic atrophic gastritis aged 33-83 years. All the participants were surveyed face to face and given the informed consent. Sociodemographic and clinical characteristics, the interpersonal sensitivity dimension of the Symptoms Checklist-90-Revised, the Trait Coping Style Questionnaire and Hospital Depression Scale were measured. A descriptive analysis and a correlation matrix were used to illuminate the characteristics of subjects and bivariate correlations, respectively. Hierarchical regression analysis and bootstrapping method were used to test the mediating effect of coping styles between interpersonal sensitivity and depression. RESULTS: The prevalence of depression among patients with chronic atrophic gastritis was 54.50%. The regression analysis revealed that interpersonal sensitivity was positively related to depression. The effect of interpersonal sensitivity on depression was partially mediated by coping styles, including positive coping and negative coping. CONCLUSIONS: Depression was highly prevalent in patients with chronic atrophic gastritis. Coping styles played a mediating role between interpersonal sensitivity and depression, which had important clinical implications for physicians and nurses. RELEVANCE TO CLINICAL PRACTICE: Patients who are at high risk of depression should be identified and applicable targets should be made for prevention and intervention, in consideration of mental health of patients with chronic atrophic gastritis.