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Although natural killer T cells (NKT cells) are altered in obese asthmatic mice, their function remains completely unclear. To further explore the potential mechanism of NKT cells in airway inflammation of obesity-associated asthma, we examined the effects of α-galactosylceramide (KRN7000) on airway inflammation in obese asthmatic mice. Male C57BL/6J mice were divided into five groups: (1) control; (2) asthma; (3) A + KRN, asthma with KRN7000; (4) obese asthma; and (5) OA + KRN, obese asthma with KRN7000. Cytometric bead array (CBA) was used to detect interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the serum. Flow cytometry was used to detect NKT cells and CD69+ NKT cells. Airway inflammation was observed in pathological sections, and calmodulin (CaM) expression was observed by immunohistochemistry in lung tissues. Airway inflammation in the obese asthma group was more severe than that of the asthma group. Airway inflammation of the OA + KRN group was reduced more than that of the A + KRN group. CD69+ NKT cells were only significantly reduced in the OA + KRN group. The levels of serum IFN-γ and TNF-α increased more in the OA + KRN group than in the A + KRN group. CaM is widely expressed in the cytoplasm of the lung tissues and was sharply decreased in the OA + KRN group. KRN7000 can significantly reduce airway inflammation in obesity-associated asthma by regulating NKT cell cytokine secretion and intracellular calcium. These results may contribute to the development of novel therapeutic approaches.

Osteoporosis (OP) is a multifactorial bone disease that occurs worldwide. The treatment of OP is still unsatisfactory. Bone mesenchymal stem cell (BMSC) differentiation is a key process in OP pathogenesis. Low-level laser irradiation (LLLI) has been reported to regulate BMSC proliferation, but the role of circRNAs in the LLLI-based promotion of BMSC proliferation remains unclear. CircRNAs are essential molecular regulators that participate in numerous biological processes and have therapeutic potential. miR-124-3p is an essential microRNA (miRNA), and its expression changes are related to BMSC proliferation ability. In the present study, gain-loss function of experiments demonstrated that circRNA_0001052 could regulate the proliferation of BMSCs by acting as a miR-124-3p sponge through the Wnt4/β-catenin pathway. The results of this study strongly suggest that circRNA_0001052 plays an essential role in BMSC proliferation in response to LLLI treatment, which is a potential therapeutic manipulation with clinical applications.

To explore the changes of a series of cytokines before and after percutaneous balloon kyphoplasty (PKP) and prognostic markers for response to PKP.From 1 January 2019 to 31 May 2019, all single-level lumbar osteoporotic vertebral compression fracture (OVCF) patients diagnosed by MRI who matched the inclusion and exclusion criteria were enrolled in this study. They were classified into the effective group and the ineffective group based on the outcome after PKP. The levels of a series of inflammatory factors and indices of spinal functions were obtained before and after PKP.A total of 72 patients were included in this study, 59 in the effective group and 13 in the ineffective group. The anterior height (AH) and posterior height (PH) were 77.3 ± 11.2% and 91.2 ± 9.3%, respectively, in the effective group after PKP, which were higher than that in the ineffective group (Our results demonstrated that PKP can reduce the serum levels of IL-6, IL-1β, and TNF-α, moreover, the IL-6, TNF-α, and AH were significant predictors of outcome.

Background Since December 2019, the outbreak of COVID-19 caused a large number of hospital admissions in China. Many patients with COVID-19 have symptoms of acute respiratory distress syndrome, even are in danger of death. This is the first study to evaluate dynamic changes of D-Dimer and Neutrophil-Lymphocyte Count Ratio (NLR) as a prognostic utility in patients with COVID-19 for clinical use. Methods In a retrospective study, we collected data from 349 hospitalized patients who diagnosed as the infection of the COVID-19 in Wuhan Pulmonary Hospital. We used ROC curves and Cox regression analysis to explore critical value (optimal cut-off point associated with Youden index) and prognostic role of dynamic changes of D-Dimer and NLR. Results 349 participants were enrolled in this study and the mortality rate of the patients with laboratory diagnosed COVID-19 was 14.9%. The initial and peak value of D-Dimer and NLR in deceased patients were higher statistically compared with survivors (P

Purpose To evaluate the clinical effect of orthokeratology in controlling myopia and treating anisometropia among children with myopic anisometropia. Methods A total of 108 myopic anisometropic children aged 8–16 years old who wore orthokeratology lenses in both eyes were enrolled in this study and followed up for over 1 year. The more severely myopic eye of each patient was assigned to the more myopic group (108 eyes), with a mean spherical equivalent refraction of −4.25 (−5.00, −3.38) D; the opposite eye of each patient was assigned to the less myopic group (108 eyes), with a refraction of −2.75 (−3.63, −1.88) D. This study observed and analyzed changes in ocular parameters after orthokeratology (Wilcoxon signed-rank test). Results In children who wore orthokeratology lenses for approximately 1 year, the level of anisometropia significantly dropped from 1.38 (1.13, 1.75) D to 1.25 (1.13, 1.75) D (P = .005). The difference between the axial lengths of the two eyes significantly dropped from 0.54 (0.37, 0.74) mm to 0.46 (0.28, 0.67) mm (P Conclusions Orthokeratology seemed to be more effective at delaying the progression of myopia in the more myopic eyes than in the less myopic eyes of myopic anisometropic children. Orthokeratology lenses are suitable for anisometropic children, although the effectiveness of orthokeratology against anisometropia requires additional follow-up time for further observation and study.

The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXR(ΔMye)LDLR(−/−)) to elucidate the role of macrophage PXR signaling in atherogenesis. The myeloid PXR deficiency did not affect metabolic phenotypes and plasma lipid profiles, but PXR(ΔMye)LDLR(−/−) mice had significantly decreased atherosclerosis at both aortic root and brachiocephalic arteries compared with control littermates. Interestingly, the PXR deletion did not affect macrophage adhesion and migration properties, but reduced lipid accumulation and foam cell formation in the macrophages. PXR deficiency also led to decreased expression of the scavenger receptor CD36 and impaired lipid uptake in macrophages of the PXR(ΔMye)LDLR(−/−) mice. Further, RNA-Seq analysis indicated that treatment with a prototypical PXR ligand affects the expression of many atherosclerosis-related genes in macrophages in vitro. These findings reveal a pivotal role of myeloid PXR signaling in atherosclerosis development and suggest that PXR may be a potential therapeutic target in atherosclerosis management.

Background Excess visceral obesity and ectopic organ fat is associated with increased risk of cardiometabolic disease. However, circulating markers for early detection of ectopic fat, particularly pancreas and liver, are lacking. Methods Lipid storage in pancreas, liver, abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from 68 healthy or pre-diabetic Caucasian and Chinese women enroled in the TOFI_Asia study was assessed by magnetic resonance imaging/spectroscopy (MRI/S). Plasma metabolites were measured with untargeted liquid chromatography–mass spectroscopy (LC–MS). Multivariate partial least squares (PLS) regression identified metabolites predictive of VAT/SAT and ectopic fat; univariate linear regression adjusting for potential covariates identified individual metabolites associated with VAT/SAT and ectopic fat; linear regression adjusted for ethnicity identified clinical and anthropometric correlates for each fat depot. Results PLS identified 56, 64 and 31 metabolites which jointly predicted pancreatic fat (R2Y = 0.81, Q2 = 0.69), liver fat (RY2 = 0.8, Q2 = 0.66) and VAT/SAT ((R2Y = 0.7, Q2 = 0.62)) respectively. Among the PLS-identified metabolites, none of them remained significantly associated with pancreatic fat after adjusting for all covariates. Dihydrosphingomyelin (dhSM(d36:0)), 3 phosphatidylethanolamines, 5 diacylglycerols (DG) and 40 triacylglycerols (TG) were associated with liver fat independent of covariates. Three DGs and 12 TGs were associated with VAT/SAT independent of covariates. Notably, comparison with clinical correlates showed better predictivity of ectopic fat by these PLS-identified plasma metabolite markers. Conclusions Untargeted metabolomics identified candidate markers of visceral and ectopic fat that improved fat level prediction over clinical markers. Several plasma metabolites were associated with level of liver fat and VAT/SAT ratio independent of age, total and visceral adiposity, whereas pancreatic fat deposition was only associated with increased sulfolithocholic acid independent of adiposity-related parameters, but not age.

Even though long non-coding RNA (lncRNA) MEG8 plays vital roles in carcinogenesis of malignances, its roles and mechanisms in hemangioma remain unknown. Therefore, we evaluate the oncogenic roles of MEG8 in hemangioma. Small interfering RNA (siRNA)-mediated depletion of MEG8 inhibited the proliferation and increased MDA level in human hemangioma endothelial cells (HemECs). The inhibitors of ferroptosis (ferrostatin-1 and liproxstatin-1) abolished the MEG8 silence induced cell viability loss. Knockdown of MEG8 increased the miR-497-5p expression and reduced the mRNA and protein levels of NOTCH2. Using a dual-luciferase assay, we confirmed the binding between MEG8 and miR-497-5p, and between the miR-497-5p and 3'UTR of NOTCH2. We further found that silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2. Importantly, blocking miR-497-5p abrogated the effects of MEG8 loss on cell viability, MDA level and expression levels of NOTCH2, SLC7A11 and GPX4 in HemECs. Taken together, our results suggested that knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis.

BACKGROUND Acute myocardial infarction is the leading cause of mortality among adults worldwide. The present study aimed to investigate the role and mechanism of thrombin and SIRT1 in hypoxia/reoxygenation (H/R) injury. MATERIAL AND METHODS H9c2 cardiomyocytes were used to create an H/R model to simulate in vivo ischemia/reperfusion injury. The MTT assay was used to measure cell viability, qRT-PCR was used to detect the level of SIRT1, thrombin, and PAR-1, and western blot analysis was conducted for evaluation of thrombin, PAR-1, SIRT1, LC3I, LC3II, and Beclin1. ELISA was applied for determination of IL-1ß, IL-6, TNF-alpha, MMP-9, and ICAM-1. After the establishment of the H/R model, superoxide dismutase (SOD) activity was evaluated by the xanthine oxidase method, malondialdehyde content was detected by thiobarbituric acid assay, and reactive oxygen species generation was measured by CM-H2DCFDA. RESULTS The findings showed that thrombin enhanced inflammatory factor secretion and oxidative stress but inhibited cell viability in H/R-injured cardiomyocytes. We also observed that thrombin promoted autophagy in H/R-injured cardiomyocytes. In addition, thrombin enhanced the upregulation of SIRT1 expression by H/R. However, it was found that inhibition of SIRT1 could suppress the effect of thrombin on inflammatory factor secretion, oxidative stress, and cell viability. Moreover, downregulation of SIRT1 suppressed the inhibitory effect of thrombin on autophagy in H/R injury. CONCLUSIONS Thrombin aggravates H/R injury of cardiomyocytes by activating an autophagy pathway mediated by SIRT1. These findings might provide a potential target therapy for the treatment of ischemia/reperfusion injury in future clinical work.

To investigate the role played by gut microbiota in the development and treatment of acute pancreatitis. Gut microbiota is the largest micro-ecosystem in the human body, and is related to various system diseases. Acute pancreatitis is one of the common acute critical diseases in clinical practice, and there are various causative factors for the occurrence of this disease, such as alcohol, infection, obstruction and intestinal microecological factors. The dysbiosis of gut microbiota may play an important role in the pathogenesis of acute pancreatitis and affect prognoses, including gut microbiota structure disorder and bacterial translocation. It can also affect host metabolism and increase the production of toxic metabolites and affect the treatment of acute pancreatitis. Probiotics are live microorganisms that can give health benefits to the host when applied in sufficient quantities, which can effectively stimulate the growth and reproduction of the normal flora of the body, inhibit the overgrowth of pathogenic bacteria, and have a protective effect on the intestinal barrier function. A search of electronic databases (PubMed, EMBASE, Cochrane) has been realized to summarize the information. The paper briefly describes the concept of gut microbiota and acute pancreatitis, examines the role of gut microbiota in the development and treatment of acute pancreatitis, concludes the investigations of the therapeutic effect of probiotics for dysbiosis of gut microbiota in acute pancreatitis in order to provide a valid reference for the development of subsequent clinical strategies.

PurposeHIV infection is consistently associated with an increased risk of atherosclerotic cardiovascular disease, but the underlying mechanisms remain elusive. HIV protein Tat, a transcriptional activator of HIV, has been shown to activate NF-κB signaling and promote inflammation in vitro. However, the atherogenic effects of HIV Tat have not been investigated in vivo. Macrophages are one of the major cell types involved in the initiation and progression of atherosclerosis. We and others have previously revealed the important role of IκB kinase β (IKKβ), a central inflammatory coordinator through activating NF-κB, in the regulation of macrophage functions and atherogenesis. This study investigated the impact of HIV Tat exposure on macrophage functions and atherogenesis.MethodsTo investigate the effects of Tat on macrophage IKKβ activation and atherosclerosis development in vivo, myeloid-specific IKKβ-deficient LDLR-deficient (IKKβΔMyeLDLR-/-) mice and their control littermates (IKKβF/FLDLR-/-) were exposed to recombinant HIV protein Tat.ResultsExposure to Tat significantly increased atherosclerotic lesion size and plaque vulnerability in IKKβF/FLDLR-/- but not IKKβΔMyeLDLR-/- mice. Deficiency of myeloid IKKβ attenuated Tat-elicited macrophage inflammatory responses and atherosclerotic lesional inflammation in IKKβΔMyeLDLR-/- mice. Further, RNAseq analysis demonstrated that HIV protein Tat affects the expression of many atherosclerosis-related genes in vitro in an IKKβ-dependent manner.ConclusionsOur findings reveal atherogenic effects of HIV protein Tat in vivo and demonstrate a pivotal role of myeloid IKKβ in Tat-driven atherogenesis.

Background: COVID-19 has been quickly spreading, making it a serious public health threat. It is important to identify phenotypes to predict the severity of disease and design an individualized treatment. Methods: We collected data from 213 COVID-19 patients in Wuhan Pulmonary Hospital from January 1 to March 30, 2020. Principal component analysis (PCA) and cluster analysis were used to classify patients. Findings: We identified three distinct subgroups of COVID-19. Cluster 1 was the largest group (52.6%) and characterized by oldest age, lowest cellular immune function and albumin levels. 38.5% of subjects were grouped into Cluster 2. Most of the lab results in Cluster 2 fell between those of Clusters 1 and 3. Cluster 3 was the smallest cluster (8.9%), characterized by youngest age and highest cellular immune function. The incidence of respiratory failure, acute respiratory distress syndrome (ARDS), heart failure and usage of non-invasive mechanical ventilation in Cluster 1 was significantly higher than others (P

Discussed in this paper is the tip-over stability analysis of a pelvic support walking robot. To improve the activities of daily living (ADL) in hemiplegic patients, a pelvic support walking robot is proposed to help patients facilitating their rehabilitation. During the gait training with the robot, the abnormal man-machine interaction forces may lead to the tip-over of the robot, which is not beneficial to the rehabilitation process. A new method is proposed to predict the possibility of tipping over and evaluate the stability of the robot based on statics model, dynamics model, and zero-moment point (ZMP) theory. Through the interaction forces and moments analysis with static case, the safe point (ZMP) is studied, and the influence factors of force/moment are analyzed by dynamics case. An optimization algorithm based on the genetic algorithm (GA) is proposed to reduce the risk of tipping over. The simulation results show that the optimization algorithm can keep the robot from tipping over when the interaction forces exceed the safety threshold.

AMD3100 is a small-molecule inhibitor of the C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) axis, while its role in aggrecan metabolism is unclear. We hypothesized that the AMD3100 modulates the transforming growth factor-β1 (TGF-β1)-induced expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) in chondrocytes. We evaluated expression of CXCL12/CXCR4 and TIMP-3 in the knee joints of rats with and without osteoarthritis (OA) by immunohistochemistry, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA). The rats were divided into sham control, destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), and DMM/phosphate-buffered saline (PBS)-treated groups. After 6 weeks, the rats were euthanized and subjected to histological and immunohistochemical analyses. Also, interleukin (IL)-1-pretreated primary chondrocytes were cultured in the presence of empty control (−, −), CXCL12a (+,−), CXCL12a + small interfering RNA (siRNA) CXCR4 (+,+), or CXCL12a + siNC (+NC), and the expression levels of target markers were evaluated by Western blotting and real-time reverse transcription PCR (RT-PCR). The CXCL12/CXCR4 levels were higher, and the expression of TIMP-3 was lower, in the OA rats compared to the healthy control rats. The rats in the DMM/AMD3100-treated group revealed a markedly decreased immunological response and mild pathology. Treatment with CXCL12a increased expression of aggrecan and disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) and suppressed that of TIMP-3 in IL-1-pretreated primary chondrocytes. TGF-β1 increased expression of TIMP-3, and this increase was reversed by CXCL12a via the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, these effects were inhibited by the CXCR4 antagonist AMD3100 and the PI3K inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY303511","term_id":"1257646067","term_text":"LY303511"}}LY303511. In conclusion, inhibition of the CXCL12a/CXCR4 signaling axis maintained TIMP-3 expression via the PI3K/Akt pathway. Our findings provide insight into the mechanism by which AMD3100 prevents OA.

Supplemental Digital Content is available in the text., Objective— The Wnt/β-catenin signaling is an ancient and evolutionarily conserved pathway that regulates essential aspects of cell differentiation, proliferation, migration and polarity. Canonical Wnt/β-catenin signaling has also been implicated in the pathogenesis of atherosclerosis. Macrophage is one of the major cell types involved in the initiation and progression of atherosclerosis, but the role of macrophage β-catenin in atherosclerosis remains elusive. This study aims to investigate the impact of β-catenin expression on macrophage functions and atherosclerosis development. Approach and Results— To investigate the role of macrophage canonical Wnt/β-catenin signaling in atherogenesis, we generated β-cateninΔmyeLDLR−/− mice (low-density lipoprotein receptor–deficient mice with myeloid-specific β-catenin deficiency). As expected, deletion of β-catenin decreased macrophage adhesion and migration properties in vitro. However, deficiency of β-catenin significantly increased atherosclerotic lesion areas in the aortic root of LDLR−/− (low-density lipoprotein receptor–deficient) mice without affecting the plasma lipid levels and atherosclerotic plaque composition. Mechanistic studies revealed that β-catenin can regulate activation of STAT (signal transducer and activator of transcription) pathway in macrophages, and ablation of β-catenin resulted in STAT3 downregulation and STAT1 activation, leading to elevated macrophage inflammatory responses and increased atherosclerosis. Conclusions— This study demonstrates a critical role of myeloid β-catenin expression in atherosclerosis by modulating macrophage inflammatory responses.

The nail is a continuous skin appendage. Cells located around the nails, which display coordinated homeostatic dynamics and release a flow of stem cells in response to regeneration, have been identified in mice. However, very few studies regarding human nail stem cells exist in the literature. Using specimens isolated from humans, we detected an unreported population of cells within the basal layer of postnatal human nail proximal folds (NPFs) and the nail matrix around the nail root. These cells were multi-expressing and expressed stem cell markers, such as keratin 15 (K15), keratin 14 (K14), keratin 19 (K19), CD29, CD34, and leucine-rich repeat-containing G protein-coupled receptor 6 (Lgr6). These cells were very similar to mouse nail stem cells in terms of cell marker expression and their location within the nail. We also found that the putative nail stem cells maintained their abundance with advancing age, but cell proliferation and nail growth rate were decreased on comparison of young and aged specimens. To summarize, we found a putative population of stem cells in postnatal human nails located at NPFs and the nail matrix. These cells may have potential for cell differentiation and be capable of responding to injury, and were retained, but may be hypofunctional during aging.

The novel mesoionic insecticide triflumezopyrim was highly effective in controlling both imidacloprid-susceptible and resistant planthopper populations in Malaysia. However, the toxicity of triflumezopyrim to planthopper populations and their natural enemies has been under-investigated in China. In this study, the median lethal concentrations (LC50) of triflumezopyrim were determined in eight field populations of Nilaparvata lugens and one population of Sogatella furcifera from China under laboratory conditions. Triflumezopyrim showed higher toxicity to planthopper populations than the commonly-used insecticide, imidacloprid. Furthermore, the lethal effect of triflumezopyrim on eight beneficial arthropods of planthoppers was investigated in the laboratory and compared with three commonly-used insecticides, thiamethoxam, chlorpyrifos and abamectin. Triflumezopyrim was harmless to Anagrus nilaparvatae, Cyrtorhinus lividipennis and Paederus fuscipes, while thiamethoxam, chlorpyrifos and abamectin were moderately harmful or harmful to the insect parasitoid and predators. Triflumezopyrim and thiamethoxam were harmless to the predatory spiders Pirata subpiraticus, Ummeliata insecticeps, Hylyphantes graminicola and Pardosa pseudoannulata, and slightly harmful to Theridion octomaculatum. Chlorpyrifos caused slight to high toxicity to four spider species except U. insecticeps. Abamectin was moderately to highly toxic to all five spider species. Our results indicate that triflumezopyrim has high efficacy for rice planthoppers populations and is compatibile with their natural enemies in China.

The objective of this study is to investigate whether the addition of double-filtration plasmapheresis (DFPP) to leflunomide and methotrexate repairs MRI bone erosion in patients with long-standing rheumatoid arthritis (RA). Seventy-two patients with highly active RA of > 3 years' duration were randomized to receive DFPP in addition to DMARDs (leflunomide and methotrexate) or DMARDs. Contrast-enhanced MRI of the right wrist was performed at months 0, 6, and 12. MRI bone erosion, synovitis, and bone edema were scored with validated methods. The primary endpoint was the change in MRI bone erosion over 12 months. Patients treated with DFPP in addition to DMARDs demonstrated significantly greater decrease in MRI erosion score compared with those treated with DMARDs, being 11.3 ± 9.6 at month 12, compared with 16.9 ± 8.3 in patients with DMARDs (P

With the promotion of inactivated poliomyelitis vaccine (IPV) and live attenuated oral poliomyelitis vaccine (OPV), the global reported cases of poliomyelitis have reduced sharply from 0.35 million in 1988 to 74 in 2015. The Polio Eradication & Endgame Strategic Plan published by WHO in 2013 included the strategy of implementation of poliovirus safe handling and containment measures to minimize the risks of facility-associated reintroduction of virus into the polio-free community to prevent the re-import of poliovirus. Toward this strategy, we produced replication-incompetent pseudovirus of poliovirus type 1, 2, 3 attenuated strains by constructing poliovirus capsid expression vectors and poliovirus replicon then transfecting HEK293T cells and developed a pseudovirus-based neutralization assay (pNA) to determine neutralizing antibody titer which is more secure, time-saving and reliable than conventional neutralization assay (cNA). By using anti-poliovirus rat serum, we demonstrated excellent correlation between neutralizing antibody titers measured by cNA and pNA. It was concluded that pNA can be a potential alternative to replace cNA as a safe and time-saving system for titer determination after live poliovirus's safekeeping.

Heat stress (HS) is a major stressor for laying hens. It causes enormous financial losses worldwide annually. The purpose of this study was to investigate the effect and mechanism of a probiotic mixture of Bacillus subtilis and Enterococcus faecium on the performance of laying hens under HS. Eight hundred and fifty-six commercial laying hens (Hy-Line Brown, aged 40 weeks) were randomly allocated to three groups, Group C (26 °C), Group H (33 °C) and Group H + PM (33 °C + probiotic mixture), respectively. The trial lasted for 20 days. Compared with Group H, we demonstrated that treatment with the probiotic mixture significantly increased the egg production rate, average daily feed intake (ADFI), and egg weight of laying hens under HS (p

Background Obesity‐associated chronic inflammation has been known to contribute to atherosclerosis development, but the underlying mechanisms remain elusive. Recent studies have revealed novel functions of IKK β (inhibitor of NF ‐κB [nuclear factor κB] kinase β), a key coordinator of inflammation through activation of NF ‐κB, in atherosclerosis and adipose tissue development. However, it is not clear whether IKK β signaling in adipocytes can also affect atherogenesis. This study aims to investigate the impact of adipocyte IKK β expression on atherosclerosis development in lean and obese LDLR (low‐density lipoprotein receptor)–deficient ( LDLR −/− ) mice. Methods and Results To define the role of adipocyte IKK β in atherogenesis, we generated adipocyte‐specific IKK β‐deficient LDLR −/− ( IKK β ΔAd LDLR −/− ) mice. Targeted deletion of IKK β in adipocytes did not affect adiposity and atherosclerosis in lean LDLR −/− mice when fed a low‐fat diet. In response to high‐fat feeding, however, IKK β ΔAd LDLR −/− mice had defective adipose remodeling and increased adipose tissue and systemic inflammation. Deficiency of adipocyte IKK β did not affect atherosclerotic lesion sizes but resulted in enhanced lesional inflammation and increased plaque vulnerability in obese IKK β ΔAd LDLR −/− mice. Conclusions These data demonstrate that adipocyte IKK β signaling affects the evolution of atherosclerosis plaque vulnerability in obese LDLR −/− mice. This study suggests that the functions of IKK β signaling in atherogenesis are complex, and IKK β in different cell types or tissues may have different effects on atherosclerosis development.

MicroRNAs (miRNAs) play pivotal roles in modulating key biological processes in gastric cancer (GC). As a newly identified miRNA, the function and potential mechanism of miR-188-5p in GC has not been thoroughly elucidated. Here, quantitative real-time polymerase chain reaction detection showed abnormally higher expression of miR-188-5p in GC cells and tissues. Gain-of-function analysis in vitro showed that miR-188-5p promoted GC cell proliferation and migration, while loss-of-function studies showed the reverse. Targetscan has predicted that phosphatase and tensin homolog (PTEN) was a potential target gene of miR-188-5p. miR-188-5p suppressed PTEN messenger RNA and protein expression and activated downstream AKT/mTOR signaling in GC cells, but luciferase reporter analysis showed that PTEN was not regulated by miR-188-5p via the 3' untranslated region. Furthermore, we observed that miR-188-5p overexpression promoted Sal-like protein 4 (SALL4) protein expression, cellular nuclear translocation, and transcription. Knockdown of SALL4 eliminated the effect of miR-188-5p in GC cells as well as suppression of PTEN. Taken together, our results demonstrate that miR-188-5p promotes GC cell proliferation and migration while suppressing tumor suppressor gene PTEN expression via transcriptional upregulation of oncogene SALL4. We conclude that miR-188-5p acts as an oncomiRNA in GC and may be a promising therapeutic target for GC.

A significant reduction in rice starch digestibility and subsequent postprandial blood glucose responses following extended cold treatment (at 4 &deg, C for 24 h) have been demonstrated in both in vitro and in vivo studies, respectively. The impact of cold treatment was more significant for parboiled rice compared to other rice varieties. This study aimed to investigate consumer liking of sensory characteristics that may influence consumer acceptability of three available rice products in the Auckland region (medium grain white, medium grain brown and parboiled rice, which were either freshly boiled or cold-treated and reheated). The consumer liking of sensory characteristics (colour, taste, flavour, and texture) of each rice sample were accessed using visual analogue scales (VAS) in a randomized single blind setting. In the second stage, the participants evaluated their acceptability on VAS after the nutritional value and the characteristics of the rice samples were revealed. Sixty-four rice consumers reported higher likings of sensory characteristics of cold-treated parboiled rice and medium grain brown rice. The effect of cold treatment on the liking of sensory characteristics was more significant for parboiled rice (p &lt, 0.05). Participants who are between 36 and 55 years old and consume rice domestically more than 10 times per month preferred cold-treated brown rice (73.8% of the participants&rsquo, population (67.4%, 80.2%)) and parboiled rice (74.3% of the participants&rsquo, population (67.9%, 80.7%)) (p &lt, 0.001). As a result, cold-treated reheated parboiled rice received higher likings and acceptability and could be recommended and accepted as a healthier replacement of the daily staple meal.

Objective. The aim of this study is to evaluate the clinical efficacy and safety of acupuncture therapy in the treatment of acute gouty arthritis.Methods. A literature search of PubMed, EMBASE, ISI Web of Science, CENTRAL, and CNKI was conducted from the inception date of each database up to October 2015. Two investigators screened each article independently and were blinded to the findings of the other reviewer. Data was extracted according to the predetermined collection form. Meta-analysis was performed.Results. We analyzed data from 28 RCTs involving 2237 patients with gouty arthritis. Compared with conventional pharmacological treatments acupuncture was more effective in rendering patients free from symptoms after 24 hours, lowering serum urate, alleviating pain associated with gouty arthritis, and decreasing the ESR; regarding CRP, no statistically significant difference was found. In addition, the frequency of adverse events in acupuncture treatment was lower than that in control group.Conclusion. Based on the findings of our study, we cautiously suggest that acupuncture is an effective and safe therapy for patients with gouty arthritis. However, the potential beneficial effect of acupuncture might be overstated due to the methodological deficiency of included studies. High quality RCTs with larger scale are encouraged.

Following the recommended use of the inactivated poliovirus vaccine from Sabin strains (sIPV) by the WHO, a D antigen-specific neutralizing monoclonal antibody (mAb) 1G10 that recognized the human poliovirus type 1 Sabin strain (PV-I Sabin) was produced for D-antigen potency evaluation on sIPV. Study of the mAb 1G10 showed that it recognized a discontinuous conformational epitope of PV-I Sabin antigen. To identify this epitope quickly, easily and cost-effectively, clues to the epitope's identity were first obtained by employing a novel mimotope strategy based on a phage display library and "in silico" prediction. Then, the conformation of the epitope region, including the amino acid sequence, neutralizing sites, and location of this epitope, was identified using several classic epitope-mapping methods such as synthesized peptides analysis, neutralization assay and site-directed mutagenesis. The mimotope strategy may offer some guidance for achieving epitope identification in a more feasible and effective way. This mAb could be used in an in-house or national and international standard IPV D-antigen potency ELISA kit in the future.

LPIN1 is a Mg(2+)-dependent phosphatidic acid phosphatase. Variation in chicken LPIN1 exon 6 and its flanking regions were identified and three indel variants in 6 breeds and their associations with performance traits were studied. Seven variants were detected from 6 breeds, which contained a synonymous tri-allelic variant (c.924A/T/C) and three indels. The exon 6 variants detected from chicken breeds were conserved among bird species. The indel variation frequency presented clear differences among breeds. Two coding indels (c.1014-1018del3 and c.1125-1138del12) were multiples of three nucleotides and maintained the open reading frames of LPIN1 proteins. However, they were predicted to result in the clear change of the RNA secondary structure of chicken LPIN1 exon 6 and LPIN1 protein conformation. The association analysis showed that c.871-15-22del6 variation had a significant effect on body weight at hatch (BW0) and 2 weeks (BW2); c. 1014-1018del3 variation had a significant effect on BW4, BW6, caecum length and gizzard weight (GW) traits; c.1125-1138del12 variation had a significant effect on BW12, shank length at 4 weeks (SL4), carcass weight, lactate dehydrogenase traits (LDH), glucose (GLU) and albumin (ALB) traits. The genotype combination for c.1014-1018del3 and c.1125-1138del12 also presented significant effects on SL4, SL8, GW, leg muscle weight, ALB, GLU and LDH. The study demonstrated that chicken LPIN1 has an important effect on body, carcass and organ weight, serum LDH, GLU and ALB level.

Background: Apoptosis of lung structural cells contributes to the process of lung damage and remodeling in chronic obstructive pulmonary disease (COPD). Our previous studies demonstrated that exogenous hydrogen sulfide (H2S) can reduce the lung tissue pathology score, anti-inflammation and anti-oxidation effects in COPD, but the effect of H2S in regulating cigarette smoke (CS) induced bronchial epithelial cell apoptosis and the underlying mechanisms are not clear. Objectives: To investigate the effect of H2S on CS induced endoplasmic reticulum stress (ERS) and bronchial epithelial cell apoptosis. Methods: Male Sprague–Dawley rats randomly divided into four groups for treatment: control, CS, NaHS + CS, and propargylglycine (PPG) + CS. The rats in the CS group were exposed to CS generated from 20 commercial unfiltered cigarettes for 4 h/day, 7 days/week for 4 months. Since the beginning of the third month, freshly prepared NaHS (14 μmol/kg) and PPG (37.5 mg/kg) were intraperitoneally administered 30 min before CS-exposure in the NaHS and PPG groups. 16HBE cells were pretreated with Taurine (10 mM), 5 mmol/L 4-phenylbutyric acid (4-PBA) or NaHS (100, 200, and 400 μM) for 30 min, and then cells were exposed to 40 μmol/L nicotine for 72 h. ERS markers (GRP94, GRP78) and ERS-mediated apoptosis markers 4-C/EBP homologous protein (CHOP), caspase-3 and caspase-12 were assessed in rat lung tissues and human bronchial epithelial cells. The apoptotic bronchial epithelial cells were detected by Hoechst staining in vitro and TUNEL staining in vivo. Results: In CS exposed rats, peritoneal injection of NaHS significantly inhibited CS induced overexpression ERS-mediated apoptosis markers and upregulation of apoptotic rate in rat lungs, and inhibiting the endogenous H2S production by peritoneal injection of PPG exacerbated these effects. In the nicotine-exposed bronchial epithelial cells, appropriate concentration of NaHS and ERS inhibitors taurine and 4-PBA inhibited nicotine-induced upregulation of apoptotic rate and overexpression of ERS-mediated apoptosis markers. Conclusion: H2S inhibited lung tissue damage by attenuating CS induced ERS in rat lung and exogenous H2S attenuated nicotine induced ERS-mediated apoptosis in bronchial epithelial cells.

Background: Globally, hot cooked refined rice is consumed in large quantities and is a major contributor to dietary glycaemic load. This study aimed to compare the glycaemic potency of hot- and cold-stored parboiled rice to widely available medium-grain white rice. Method: Twenty-eight healthy volunteers participated in a three-treatment experiment where postprandial blood glucose was measured over 120 min after consumption of 140 g of rice. The three rice samples were freshly cooked medium-grain white rice, freshly cooked parboiled rice, and parboiled rice stored overnight at 4 °C. All rice was served warm at 65 °C. Chewing time was recorded. Results: incremental area under the curve (iAUC) of the control rice, freshly cooked medium-grain white rice, was the highest: 1.7-fold higher (1.2, 2.6) than reheated parboiled rice (p < 0.001) and 1.5-fold higher (1.0, 2.2) than freshly cooked parboiled rice (p = 0.001). No significant difference in postprandial glycaemic response was observed between freshly cooked and reheated parboiled rice samples (p = 0.445). Chewing time for 10 g cold-stored parboiled rice was 6 s (25%) longer and was considered more palatable, visually appealing and better tasting than freshly cooked medium-grain (all p < 0.05). Conclusions: For regular consumers of rice, reheating cooked rice after cold storage would lower the dietary glycaemic load and, in the long term, may reduce the risk for type 2 and gestational diabetes. More trials are needed to identify the significance.

NADH dehydrogenase subunit 2 gene (ND2) is one of the mitochondrial DNA (mtDNA) protein coding genes, which is a subunit of NADH dehydrogenase. The main purpose of this study was to investigate the variation/heteroplasmic sites of chicken ND2, and thus to evaluate the association with chicken growth traits, carcass traits, and serum biochemical indexes. Seventeen variants were detected in the ND2 gene by Sanger sequencing, which constructed 15 haplotypes; the haplotype diversity (hd) was 0.7692. Mt.A5703T and mt.T5727G in the ND2 gene had been detected as the heteroplasmic sites via the created restriction site restriction fragment length polymorphism (CRS-PCR-RFLP) method. Moreover, the study on distribution of two heteroplasmic variants in the Gushi chicken F2 resource population revealed that the heteroplasmic ratio of mt.A5703T and mt.T5727G was 9% and 40%, respectively. It showed that there was obvious heteroplasmic difference between two sites. Association analysis of the variation/heteroplasmy with the related traits in Gushi chicken F2 population showed that the mt.A5703T and mt.T5727G were significantly associated with the pectoral muscle fat content and the duodenum length, but no significance was found with body weight (BW). It was the first time to indicate that heteroplasmic variation had significant effect on growth traits, carcass parameters, and meat quality traits, which showed the potential importance of related variation.

Chicken mitochondrial DNA is a circular molecule comprising ~16.8 kb. In this study, we used next-generation sequencing to investigate mitochondrial heteroplasmy in the whole chicken mitochondrial genome. Based on heteroplasmic detection thresholds at the 0.5% level, 178 cases of heteroplasmy were identified in the chicken mitochondrial genome, where 83% were due to nucleotide transitions. D-loop regionwas hot spot region for mtDNA heteroplasmy in the chicken since 130 cases of heteroplasmy were located in these regions. Heteroplasmy varied among intraindividual tissues with allele-specific, position-specific, and tissue-specific features. Skeletal muscle had the highest abundance of heteroplasmy. Cases of heteroplasmy at mt.G8682A and mt.G16121A were validated by PCR-restriction fragment length polymorphism analysis, which showed that both had low ratios of heteroplasmy occurrence in five natural breeds. Polymorphic sites were easy to distinguish. Based on NGS data for crureus tissues, mitochondrial mutation/heteroplasmy exhibited clear maternal inheritance features at the whole mitochondrial genomic level. Further investigations of the heterogeneity of the mt.A5694T and mt.T5718G transitions between generations using pyrosequencing based on pedigree information indicated that the degree of heteroplasmy and the occurrence ratio of heteroplasmy decreased greatly from the F0 to F1 generations in the mt.A5694T and mt.T5718G site. Thus, the intergenerational transmission of heteroplasmy in chicken mtDNA exhibited a rapid shift toward homoplasmy within a single generation. Our findings indicate that heteroplasmy is a widespread phenomenon in chicken mitochondrial genome, in which most sites exhibit low heteroplasmy and the allele frequency at heteroplasmic sites changes significantly during transmission events. It suggests that heteroplasmy may be under negative selection to some degree in the chicken.

Introduction: Nasopharyngeal carcinoma is the most common cancer originating from the nasopharynx. Objective: To study the mechanisms of nasopharyngeal carcinoma, we analyzed GSE12452 microarray data. Methods: GSE12452 was downloaded from the Gene Expression Omnibus database and included 31 nasopharyngeal carcinoma samples and 10 normal nasopharyngeal tissue samples. The differentially expressed genes were screened by ANOVA in the PGS package. Using the BiNGO plugin in Cytoscape and pathway enrichment analysis in the PGS package, functional and pathway enrichment analyses were performed separately to predict potential functions of the differentially expressed genes. Furthermore, Transcription factor-differentially expressed gene pairs were searched, and then the transcription factor-differentially expressed gene regulatory network was visualized using Cytoscape software. Results: A total of 487 genes were screened as differentially expressed genes between the nasopharyngeal carcinoma samples and the normal nasopharyngeal tissue samples. Enrichment analysis indicated that PTGS2 was involved in the regulation of biological process and small cell lung cancer. ZIC2 and OVOL1 may function in nasopharyngeal carcinoma through targeting significantly up-regulated genes (such as PTGS2, FN1, CXCL9 and CXCL10) in the Transcription factor-differentially expressed gene regulatory network (e.g., ZIC2→PTGS2 and OVOL1→CXCL10). Conclusion: PTGS2, FN1, CXCL9, CXCL10, ZIC2 and OVOL1 might play roles in nasopharyngeal carcinoma. Resumo Introdução: O carcinoma nasofaríngeo é o câncer mais comum originário da nasofaringe. Objetivo: Estudar os mecanismos do câncer de nasofaringe; dados do microarray GSE12452 foram analisados. Método: GSE12452 foi obtido da base de dados Gene Expression Omnibus e inclui 31 amostras de carcinoma nasofaríngeo e 10 amostras de tecido nasofaríngeo normal. Os genes diferencialmente expressos foram analisados por ANOVA no kit PGS. Usando o plugin BiNGO no Cytoscape e análise de enriquecimento da via no kit PGS, análises de enriquecimento funcional e da via foram realizadas separadamente para prever as potenciais funções dos genes diferencialmente expressos. Além disso, os pares Fator de Transcrição - genes diferencialmente expressos foram pesquisados e em seguida a sua rede reguladora foi visualizada usando o programa Cytoscape. Resultados: Um total de 487 genes foram analisados como genes diferencialmente expressos entre as amostras de carcinoma nasofaríngeo e amostras de tecido nasofaríngeo normal. A análise de enriquecimento indicou que PTGS2 estava envolvido na regulação do processo biológico e câncer pulmonar de pequenas células. ZIC2 e OVOL1 podem funcionar no carcinoma nasofaríngeo almejando-se de maneira significativa os genes suprarregulados (como o PTGS2, FN1, CXCL9 e CXCL10) na rede reguladora de fator de transcrição - genes diferencialmente expressos (p.ex., ZIC2→PTGS2 e OVOL1→CXCL10). Conclusão: PTGS2, FN1, CXCL9, CXCL10, ZIC2 e OVOL1 podem desempenhar alguns papéis no carcinoma de nasofaringe.

Background Enteric-type glandular lesions are extremely rare in the vagina. Their histological origin remains a matter of speculation at present. Method We review two rectal mucosal prolapse-like polyps and one intestinal-type adenosis in the vagina. Results Case 1, a 64-year-old woman, presented with a vaginal polypoid lesion with a size of 4 × 3 × 3 cm. Case 2, an 8-year-old girl, had a 1.5 × 1.5 × 0.8-cm pedunculated polyp in the vaginal navicular fossa and a clinically suspected rectovaginal fistula. Case 1 and 3 had an obsolete severe perineal laceration. On histopathological examination, cases 1 and 2 resembled rectal mucosal prolapse or inflammatory cloacogenic polyp (rectal mucosal prolapse-like polyp). Case 3 had an incidental intestinal-type adenosis in the removed vaginal wall. Immunohistochemistry confirmed the intestinal differentiation in all 3 lesions by showing diffuse CDX2-positive, CK20-positive, and scattered chromogranin A-positive neuroendocrinal cells in the lower compartment of the crypt. Conclusions In summary, we report herein three unusual cases of benign intestinal-type glandular lesions in the vagina including two rectal mucosal prolapse-like polyps and one case of intestinal-type adenosis, and discuss possibilities for their histogenetic basis.

Subunit 2 of NADH dehydrogenase (ND2) is encoded by the mt-ND2 gene and plays a critical role in controlling the production of the mitochondrial reactive oxygen species. Our study focused on exploring the mt-ND2 tissue expression patterns and the effects of energy restriction and dietary fat (linseed oil, corn oil, sesame oil or lard) level (2.5% and 5%) on its expression in chicken. The results showed that mt-ND2 gene was expressed in the 15 tissues of hybrid chickens with the highest level in heart and lowest level in pancreas tissue; 30% energy restriction did not significantly affect mt-ND2 mRNA level in chicken liver tissue. Both the mt-ND2 mRNA levels in chicken pectoralis (p < 0.05) and hepatic tissues (p < 0.05) at 42 d-old were affected by the type of dietary fats in 5% level, while not in abdominal fat tissues. The expression of mt-ND2 in hepatic tissues was down-regulated with chicken age (p < 0.01). The interactive effect of dietary fat types with chicken age (p < 0.05) was significant on mt-ND2 mRNA level. The study demonstrated that mt-ND2 gene was extensively expressed in tissues, and the expression was affected by dietary fat types and chicken age.

We evaluated the role of the CXCL12/CXCR4 (C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4) axis in aggrecanase-mediated cartilage degradation, and explored the underlying mechanism in a post-traumatic osteoarthritis rat model. Expression of CXCL12/CXCR4 and ADAMTS-5 was analyzed in the knees of osteoarthritic and non-arthritic rats using Western blot, ELISA, immunohistochemistry and immunofluorescence. Rodent studies were performed using Sprague-Dawley rats, with animals divided into three groups: Destabilization of the medial meniscus/AMD3100-treated (DMM/AMD3100-treated), DMM/PBS-treated, and sham controls. Rats were sacrificed after eight weeks, and samples were collected for histology and immunohistochemistry analyses. IL-1-pretreated primary chondrocytes were cultured with untreated control, CXCL12a, siNC + CXCL12a, or siRNA CXCR4 + CXCL12a, and analyzed for expression of relevant markers and cellular pathways. Higher levels of CXCL12 were detected in the knee fluid of osteoarthritic subjects, with strong staining for CXCR4 in chondrocytes and CXCL12 in synoviocytes together with enhanced expression of ADAMTS-5. DMM/AMD3100-treated rats showed a significantly reduced immunological response, with minimal evidence of pathology in both histological and immunohistochemical analyses. Treatment with CXCL12a increased the expression of ACAN, RUNX-2, and ADAMTS-4/5 in IL-1-pretreated primary chondrocytes, together with a decrease in the expression of SOX-9. Molecular analyses revealed strong induction of NF-κB activation, along with phosphorylation of MAPKs, and activation of canonical Wnt/β-catenin signaling. In conclusion, inhibition of SDF-1α/CXCR4 signaling axis was able to inhibit aggrecanase expression and lessen cartilage degeneration in post-traumatic osteoarthritis rats.