A systematic review and meta-analysis of canine enteric coronavirus prevalence in dogs of mainland China.

BACKGROUND: Canine enteric coronavirus (CECoV) is a prevalent infectious disease among dogs worldwide, yet its epidemiology in mainland China remains poorly understood. This systematic review and meta-analysis aimed to assess the prevalence of CECoV in mainland China and identify factors influencing its prevalence. METHODS: A comprehensive literature search was conducted across multiple databases for studies regarding CECoV epidemiology of China. PubMed, CNKI, Wanfang, and CQVIP were searched to obtain the studies. Eligible studies were selected based on predefined criteria, and data were extracted and synthesized. The quality the studies was assessed using the JBI assessment tool. Heterogeneity was checked using I2 test statistics followed by subgroup and sensitivity analysis. Subgroup analyses were performed to explore variations in CECoV prevalence by factors such as year, region, season, health status, social housing type, gender, age, and breed. Publication bias was assessed using a funnel plot and eggers test that was followed by trim and fill analysis. RESULTS: A total of 27 studies involving 21,034 samples were included in the meta-analysis. The overall pooled prevalence of CECoV in mainland China was estimated to be 0.30 (95% CI 0.24-0.37), indicating persistent circulation of the virus. Subgroup analyses revealed higher prevalence rates in younger dogs, multi-dog households, apparently healthy dogs, and certain regions such as southwest China. Seasonal variations were observed, with lower prevalence rates in summer. However, no significant differences in prevalence were found by gender. CONCLUSIONS: This study provides valuable insights into the epidemiology of CECoV in mainland China, highlighting the persistent circulation of the virus and identifying factors associated with higher prevalence rates. Continuous monitoring and surveillance efforts, along with research into accurate detection methods and preventive measures, are essential for the effective control of CECoV and mitigation of its potential impact on animal and human health.

Relationship between gut microbiota and the pathogenesis of gestational diabetes mellitus: a systematic review.

Introduction: Gestational diabetes mellitus (GDM) is a form of gestational diabetes mellitus characterized by insulin resistance and abnormal function of pancreatic beta cells. In recent years, genomic association studies have revealed risk and susceptibility genes associated with genetic susceptibility to GDM. However, genetic predisposition cannot explain the rising global incidence of GDM, which may be related to the increased influence of environmental factors, especially the gut microbiome. Studies have shown that gut microbiota is closely related to the occurrence and development of GDM. This paper reviews the relationship between gut microbiota and the pathological mechanism of GDM, in order to better understand the role of gut microbiota in GDM, and to provide a theoretical basis for clinical application of gut microbiota in the treatment of related diseases. Methods: The current research results on the interaction between GDM and gut microbiota were collected and analyzed through literature review. Keywords such as "GDM", "gut microbiota" and "insulin resistance" were used for literature search, and the methodology, findings and potential impact on the pathophysiology of GDM were systematically evaluated. Results: It was found that the composition and diversity of gut microbiota were significantly associated with the occurrence and development of GDM. Specifically, the abundance of certain gut bacteria is associated with an increased risk of GDM, while other changes in the microbiome may be associated with improved insulin sensitivity. In addition, alterations in the gut microbiota may affect blood glucose control through a variety of mechanisms, including the production of short-chain fatty acids, activation of inflammatory pathways, and metabolism of the B vitamin group. Discussion: The results of this paper highlight the importance of gut microbiota in the pathogenesis of GDM. The regulation of the gut microbiota may provide new directions for the treatment of GDM, including improving insulin sensitivity and blood sugar control through the use of probiotics and prebiotics. However, more research is needed to confirm the generality and exact mechanisms of these findings and to explore potential clinical applications of the gut microbiota in the management of gestational diabetes. In addition, future studies should consider the interaction between environmental and genetic factors and how together they affect the risk of GDM.

Epidemiological Analysis of Global and Regional Lung Cancer Mortality: Based on 30-Year Data Analysis of Global Burden Disease Database.

The objective of this study was to understand dynamic global and regional lung cancer fatality trends and provide a foundation for effective global lung cancer prevention and treatment strategies. Data from 1990 to 2019 were collected from the Global Burden Disease (GBD) database and statistical analysis was conducted using Excel 2010. Standardization was based on the GBD's world population structure, and the Average Annual Percentage Change (AAPC) was calculated using Joinpoint 4.8.0.1 software. Bayesian age-period-cohort analysis (BAPC) predicted global lung cancer mortality from 2020 to 2030. In 2019, worldwide lung cancer deaths reached 2,042,600, a 91.75% increase from 1990 (1,065,100). The standardized age-specific death rate in 2019 was 25.18 per 100,000. Males had a rate of 37.38 while females had 14.99. Men saw a decreasing trend while women experienced an increase. High- and medium-high-SDI regions had declining rates (-0.3 and -0.8 AAPCs) whereas middle-, low-, and low-middle-SDI regions had increased mortality rates (AAPC = 0.1, AAPC = 0.37, AAPC = 0.13). Several regions, including Oceania, South Asia, East Asia, Western Sub-Saharan Africa, Southeast Asia, and Eastern Sub-Saharan Africa, witnessed rising global lung cancer mortality rates (p < 0.01). The global standardized mortality rate for lung cancer is expected to decrease from 2020 to 2030, but predictions indicate increasing female mortality and decreasing male mortality. Despite overall declines, rising female mortality remains a concern. Effective measures are essential to reduce mortality rates and improve patients' quality of life in the global fight against lung cancer.

[Angiotensin converting enzyme 2 alleviates infectious bronchitis virus-induced cellular inflammation by suppressing IL-6/JAK2/STAT3 signaling pathway].

The goal of this study was to investigate the regulatory effect of angiotensin converting enzyme 2 (ACE2) on cellular inflammation caused by avian infectious bronchitis virus (IBV) and the underlying mechanism of such effect. Vero and DF-1 cells were used as test target to be exposed to recombinant IBV virus (IBV-3ab-Luc). Four different groups were tested: the control group, the infection group[IBV-3ab-Luc, MOI (multiplicity of infection)=1], the ACE2 overexpression group[IBV-3ab Luc+pcDNA3.1(+)-ACE2], and the ACE2-depleted group (IBV-3ab-Luc+siRNA-ACE2). After the cells in the infection group started to show cytopathic indicators, the overall protein and RNA in cell of each group were extracted. real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the mRNA expression level of the IBV nucleoprotein (IBV-N), glycoprotein 130 (gp130) and cellular interleukin-6 (IL-6). Enzyme linked immunosorbent assay (ELISA) was used to determine the level of IL-6 in cell supernatant. Western blotting was performed to determine the level of ACE2 phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). We found that ACE2 was successfully overexpressed and depleted in both Vero and DF-1 cells. Secondly, cytopathic indicators were observed in infected Vero cells including rounding, detaching, clumping, and formation of syncytia. These indicators were alleviated in ACE2 overexpression group but exacerbated when ACE2 was depleted. Thirdly, in the infection group, capering with the control group, the expression level of IBV-N, gp130, IL-6 mRNA and increased significantly (P < 0.05), the IL-6 level was significant or extremely significant elevated in cell supernatant (P < 0.05 or P < 0.01); the expression of ACE2 decreased significantly (P < 0.05); protein phosphorylation level of JAK2 and STAT3 increased significantly (P < 0.05). Fourthly, comparing with the infected group, the level of IBV-N mRNA expression in the ACE2 overexpression group had no notable change (P > 0.05), but the expression of gp130 mRNA, IL-6 level and expression of mRNA were elevated (P < 0.05) and the protein phosphorylation level of JAK2 and STAT3 decreased significantly (P < 0.05). In the ACE2-depleted group, there was no notable change in IBV-N (P > 0.05), but the IL-6 level and expression of mRNA increased significantly (P < 0.05) and the phosphorylation level of JAK2 and STAT3 protein decreased slightly (P > 0.05). The results demonstrated for the first time that ACE2 did not affect the replication of IBV in DF-1 cell, but it did contribute to the prevention of the activation of the IL-6/JAK2/STAT3 signaling pathway, resulting in an alleviation of IBV-induced cellular inflammation in Vero and DF-1 cells.

The global, regional and national burden of type 2 diabetes mellitus in the past, present and future: a systematic analysis of the Global Burden of Disease Study 2019.

Aim: To report the global, regional, and national burden of type 2 diabetes mellitus (T2DM) in 2019, assess its trends in the past, and forecast its trends in the future. Methods: The main data source was the Global Burden of Disease 2019 database. We assessed the changes in T2DM burden from 1990 to 2019 with joinpoint regression analysis. Age-period-cohort analysis was used to forecast the T2DM incidence and mortality rate from 2020 to 2034. Results: The burden of T2DM has increased from 1990 to 2019 generally. The low-middle socio-demographic index (SDI) region had the highest increase in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life years (ASDR) due to T2DM. Nationally, the increase in ASIR (r=0.151, p=0.046) and the decrease in ASMR (r=0.355, p<0.001) were positively correlated with SDIs. In 2019, the global ASIR, ASPR, ASMR, ASDR due to T2DM were 259.9 (95% UI 240.3-281.4), 5282.9 (95% UI 4853.6-5752.1), 18.5 (95% UI 17.2-19.7), and 801.5 (95% UI 55477000-79005200) per 100,000 population, respectively. Additionally, the ASIR (r=0.153, p=0.030) and ASPR (r=0.159, p=0.024) of T2DM were positively correlated with SDIs, while ASMR (r=-0.226, p=0.001) and ASDR (r=-0.171, p=0.015) due to T2DM were negatively correlated with SDIs. The ASIR was estimated to increase to 284.42, and ASMR was estimated to increase to 19.1 from 2030 to 2034, per 100,000 population. Conclusion: Globally, the burden of T2DM has increased in the past and was forecast to continue increasing. Greater investment in T2DM prevention is needed.

Comparison and Suggestions of Logistics Performance Index of Main Countries of Belt and Road Strategy Based on Bootstrap DEA Model.

As an important economic sector, logistics is becoming more important, if not crucial, in economic growth. In our nation, the logistics industry is booming, and it's just getting better. However, in addition to focusing on the positive aspects of our country's logistics industry's development, we should also analyze and address the negative aspects of our country's logistics industry's development. The overall logistics pattern has not yet been formed, and there is an urgent need for systematic construction. The regional development is extremely unbalanced. By comparing the logistics performance indices of various Belt and Road countries, this research aims to examine the major elements influencing overall logistics performance. Second, we introduce the Moran index to explore the geographical association of the subdivision indicators of the logistics performance index using the spatial econometric model. The bootstrap DEA analysis method examines and ranks the countries' logistics performance indexes, determines our country's advantages and disadvantages in comparison to other Belt and Road countries, and executes specific improvement strategies that will enhance logistics and boost the overall growth of our country's logistics sector.

MSC-ACE2 Ameliorates Streptococcus uberis-Induced Inflammatory Injury in Mammary Epithelial Cells by Upregulating the IL-10/STAT3/SOCS3 Pathway.

In the dairy industry, Streptococcus uberis (S. uberis) is one of the most important pathogenic bacteria associated with mastitis in milk-producing cows, causing vast economic loss. To date, the only real effective method of treating and preventing streptococcal mastitis is antimicrobial therapy. In many inflammatory diseases, mesenchymal stem cells (MSCs) and angiotensin-converting enzyme 2 (ACE2) play an anti-inflammatory and anti-injurious role. Accordingly, we hypothesized that MSCs overexpressing ACE2 (MSC-ACE2) would ameliorate the inflammatory injury caused by S. uberis in mammary epithelial cells more efficiently than MSC alone. By activating the transcription 3/suppressor of cytokine signaling 3 (IL-10/STAT3/SOCS3) signaling pathway, MSC-ACE2 inhibited the NF-κB, MAPKs, apoptosis, and pyroptosis passways. Moreover, MSC-ACE2 overturned the downregulation of Occludin, Zonula occludens 1 (ZO-1), and Claudin-3 expression levels caused by S. uberis, suggesting that MSC-ACE2 promotes the repair of the blood-milk barrier. MSC-ACE2 demonstrated greater effectiveness than MSC alone, as expected. Based on these results, MSC-ACE2 effectively inhibits EpH4-Ev cell's inflammatory responses induced by S. uberis, and would be an effective therapeutic tool for treating streptococcal mastitis.

Overexpression of angiotensin-converting enzyme 2 contributes to the amelioration of Streptococcus uberis-induced inflammatory injury in mammary epithelial cells.

Streptococcus uberis (S. uberis) is an environmentally important pathogenic bacterium and is the main pathogenic microorganism responsible for mastitis, which causes significant economic losses worldwide. Currently, there is no particularly effective treatment other than antibiotic therapy. Angiotensin-converting enzyme 2 (ACE2) plays an anti-inflammatory as well as an anti-injury role in numerous inflammatory diseases. Therefore, this study aimed to assess the hypothesis that S. uberis-induced mammary epithelial cells injury associated with ACE2, angiotensin II (Ang II) as well as angiotensin 1-7 (Ang-(1-7)) imbalance and that overexpression of ACE2 can repair S. uberis-induced mammary epithelial cells injury. We observed that the expression level of ACE2 was significantly downregulated after treatment of EpH4-Ev cells with S. uberis. Next, this assay verified the role of ACE2 in S. uberis-induced inflammatory injury in EpH4-Ev cells by overexpressing the ACE2 gene as well as its silencing. The results showed that overexpression of the ACE2 gene significantly activated the interleukin-10/signal transducer and activator of transcription 3/suppressors-of-cytokine-signaling 3 (IL-10/STAT3/SOCS3) pathway, thereby inhibiting the nuclear factor-κB (NF-κB) as well as pyroptosis pathways. Furthermore, overexpression of the ACE2 gene reversed the downregulation of zonula occludens 1 (ZO-1), Occludin, Claudin-1, and Claudin-2 caused by S. uberis, suggesting that ACE2 could promote to repair the blood-milk barrier. However, siRNA silencing of the ACE2 gene produced the opposite effect. These results suggest that ACE2 ameliorates S. uberis-induced mammary epithelial cells injury. AVAILABILITY OF DATA: All data generated or analyzed during this study are included within the article and its additional information file.

ACE2 suppresses the inflammatory response in LPS-induced porcine intestinal epithelial cells via regulating the NF-κB and MAPK pathways.

ACE2 can regulate the development of intestinal inflammatory response, while the effect on LPS-induced inflammatory changes in porcine intestinal epithelial cells is still unclear. The present study investigated the role of ACE2 in inflammatory injury and the possible signaling pathways. The current results show that LPS cause inflammatory damage in IPEC-J2 cells and local RAS system was activated, with a significant correlation. ACE2 gene of IPEC-J2 cells are knocked down, and the inflammatory response are aggravated. ACE2 resist LPS-induced inflammation by degrading Ang II to produce Ang (1-7). The anti-inflammatory effect of ACE2 are mainly achieved by regulating the phosphorylation level of p65 in the NF-κB pathway and ERK1/2 in the MAPK pathway, reducing the expression and release of cellular inflammatory factors. These results reveal the biochemical mechanism of ACE2 against cellular inflammatory response and its potential application.

Effect of Dihydropyridine Calcium Channel Blocker on Mortality of Hypertension Patients With Moderate-Severe Pulmonary Acute Respiratory Distress Syndrome: A Multicenter Retrospective Observational Cohort Study.

The aim was to evaluate the effect of dihydropyridine calcium channel blocker on the prognosis for moderate-severe pulmonary acute respiratory distress syndrome in hypertension patients. DESIGN: A retrospective, observational, multicenter cohort study. SETTING: A total of 307 patients without propensity score matching and 186 adult inpatients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome in five teaching hospitals in Jiangsu province, China, from December 2015 to December 2020 were enrolled. PATIENTS: A total of 307 patients without propensity score matching and 186 patients with propensity score matching diagnosed with hypertension and moderate-severe pulmonary acute respiratory distress syndrome were included in the final analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic characteristics and clinical characteristics were recorded. The propensity score matching method was used to eliminate the difference between group with dihydropyridine calcium channel blocker and group without dihydropyridine calcium channel blocker. The primary outcome was in-hospital mortality. We used univariate and multivariate regression analyses for both patients with or without propensity score matching to assess the effect of these variables on mortality. In the subset of 186 patients with propensity score matching, in-hospital mortality was 53.2%. Inpatient mortality was significantly higher in patients treated with dihydropyridine calcium channel blocker than in those not treated with dihydropyridine calcium channel blocker of patients without propensity score matching (65.4% vs 40.4%; p < 0.01). Multivariate analysis for patients without propensity score matching showed that dihydropyridine calcium channel blocker (hazard ratio, 1.954; 95% CI, 1.415-2.699), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 3.809; 95% CI, 2.106-4.531), and lactate greater than or equal to 2 mmol/L (hazard ratio, 1.454; 95% CI, 1.041-2.029) were independently associated with in-hospital mortality. Based on univariate analysis for patients with propensity score matching, dihydropyridine calcium channel blocker (hazard ratio, 2.021; 95% CI, 1.333-3.064), lactate dehydrogenase greater than or equal to 600 U/L (hazard ratio, 4.379; 95% CI, 2.642-7.257), and lactate greater than or equal to 2 mmol/L (hazard ratio, 2.461; 95% CI, 1.534-3.951) were independently associated with in-hospital mortality. In contrast, patients not treated with dihydropyridine calcium channel blocker had a significant survival advantage over those treated with dihydropyridine calcium channel blocker in both patients without or with propensity score matching (p < 0.001; p = 0.001 by Kaplan-Meier analysis). CONCLUSIONS: Dihydropyridine calcium channel blocker, lactate dehydrogenase greater than or equal to 600 U/L, and lactate greater than or equal to 2 mmol/L at admission were independent risk factors for patients with hypertension and moderate-severe pulmonary acute respiratory distress syndrome.

lncRNA HAND2-AS1 overexpression inhibits cancer cell proliferation in hepatocellular carcinoma by downregulating RUNX2 expression.

BACKGROUND: The long non-coding RNA HAND2 antisense RNA 1 (HAND2-AS1) acts as a tumor suppressor in several malignancies, but its role in hepatocellular carcinoma (HCC) remains unknown. In this study, we aimed to investigate the function of HAND2-AS1 in HCC. METHODS: The expression levels of HAND2-AS1 and runt-related transcription factor 2 (RUNX2) were determined in patients with HCC and HCC cell lines using quantitative real-time polymerase chain reaction and western blot analyses. Cell proliferation was determined using Cell Counting Kit-8 assay, and the correlation between HAND2-AS1 and RUNX2 expression was also investigated. RESULTS: The plasma level of HAND2-AS1 was downregulated and that of RUNX2 was upregulated in patients with early-stage HCC compared with those in healthy controls. No significant differences in the plasma levels of HAND2-AS1 and RUNX2 were found among hepatitis B virus (HBV)-positive, hepatitis C virus (HCV)-positive, and HBV- and HCV-negative patients with HCC. The plasma levels of HAND2-AS1 and RUNX2 were inversely correlated in the patient groups but not in the control group. HAND2-AS1 overexpression led to the downregulation of RUNX2 expression in human HCC cells, whereas RUNX2 failed to significantly affect HAND2-AS1 expression. HAND2-AS1 overexpression inhibited and RUNX2 overexpression promoted the proliferation of HCC cells. RUNX2 overexpression attenuated the inhibitory effects of HAND2-AS1 overexpression on cancer cell proliferation. CONCLUSION: HAND2-AS1 overexpression inhibits cancer cell proliferation in HCC by downregulating RUNX2 expression.

Diallyl disulfide induces downregulation and inactivation of cofilin 1 differentiation via the Rac1/ROCK1/LIMK1 pathway in leukemia cells.

Cofilin is associated with cell differentiation; however, to the best of our knowledge, no data have indicated an association between the cofilin 1 pathway and leukemia cell differentiation. The present study investigated the involvement of the cofilin 1 signaling pathway in diallyl disulfide (DADS)­induced differentiation and the inhibitory effects on the proliferation, migration, and invasion of human leukemia HL­60 cells. First, it was identified that 8 µM DADS suppressed cell proliferation, migration and invasion, and induced differentiation based on the reduced nitroblue tetrazolium ability and increased CD11b and CD33 expression. DADS significantly downregulated the expression of cofilin 1 and phosphorylated cofilin 1 in HL­60 leukemia cells. Second, it was verified that silencing cofilin 1 markedly promoted 8 µM DADS­induced differentiation and the inhibitory effect on cell proliferation and invasion. Overexpression of cofilin 1 obviously suppressed 8 µM DADS­induced differentiation and the inhibitory effect on cell proliferation and invasion. Third, the present study examined the mechanisms by which 8 µM DADS decreases cofilin 1 expression and activation. The results revealed that 8 µM DADS inhibited the mRNA and protein expression of Rac1, Rho­associated protein kinase 1 (ROCK1) and LIM domain kinase 1 (LIMK1) as well as the phosphorylation of LIMK1 in HL­60 cells, while 8 µM DADS enhanced the effects of the Rac1­ROCK1­LIMK1 pathway in cells overexpressing cofilin 1 compared with that in control HL­60 cells. These results suggest that the anticancer function of DADS on HL­60 leukemia cells is regulated by the Rac1­ROCK1­LIMK1­cofilin 1 pathway, indicating that DADS could be a promising anti­leukemia therapeutic compound.

THBS1/CD47 Modulates the Interaction of γ-Catenin With E-Cadherin and Participates in Epithelial-Mesenchymal Transformation in Lipid Nephrotoxicity.

Hyperlipidemia, an important risk factor for cardiovascular and end-stage renal diseases, often aggravates renal injury and compromises kidney function. Here, histological analysis of human kidney samples revealed that high lipid levels induced the development of renal fibrosis. To elucidate the mechanism underlying lipid nephrotoxicity, we used two types of mouse models (Apoe-/- and C57BL/6 mice fed a 45 and 60% high-fat diet, respectively). Histological analysis of kidney tissues revealed high-lipid-induced renal fibrosis and inflammation; this was confirmed by examining fibrotic and inflammatory marker expression using Western blotting and real-time polymerase chain reaction. Oxidized low-density lipoprotein (OX-LDL) significantly induced the fibrotic response in HK-2 tubular epithelial cells. RNA-sequencing and Gene Ontology analysis of differentially expressed mRNAs in OX-LDL-treated HK-2 tubular epithelial cells and real-time PCR validation in Apoe-/- mice showed that the expression of thrombospondin-1 (THBS1) in the high-fat group was significantly higher than that of the other top known genes, along with significant overexpression of its receptor CD47. THBS1 knockdown cells verified its relation to OX-LDL-induced fibrosis and inflammation. Liquid chromatography tandem mass spectrometry and STRING functional protein association network analyses predicted that THBS1/CD47 modulated the interaction between γ-catenin and E-cadherin and was involved in epithelial-mesenchymal transition, which was supported by immunoprecipitation and immunohistochemistry. CD47 downregulation following transfection with small-hairpin RNA in OX-LDL-treated tubular epithelial cells and treatment with anti-CD47 antibody restored the expression of E-cadherin and attenuated renal injury, fibrosis, and inflammatory response in OX-LDL-treated cells and in type 2 diabetes mellitus. These findings indicate that CD47 may serve as a potential therapeutic target in long-term lipid-induced kidney injury.

Rosiglitazone Reduces Apoptosis and Inflammation in Lipopolysaccharide-Induced Human Umbilical Vein Endothelial Cells.

BACKGROUND Although the peroxisome proliferator-activated receptor-g (PPARg) agonist rosiglitazone has significant anti-inflammatory properties, no scientific studies have provided new insights in its pharmacological properties with respect to acute respiratory distress syndrome (ARDS). The present investigation aimed to evaluate whether rosiglitazone can reduce apoptosis and inflammation in a lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in vitro model. MATERIAL AND METHODS Human umbilical vein endothelial cells (HUVECs) were treated with 1 µg/ml LPS in the absence or presence of 10 µM rosiglitazone for 24 h. Cell viability was measured by MTT assay. Flow cytometry was used to examine the cell apoptosis and ROS production in HUVECs response to LPS and rosiglitazone. The levels of pro-inflammatory cytokine factors, including TNF-α, IL-6, CXCL12, and CXCR4, were measured by ELISA, real-time PCR, and Western blot assay, respectively. The expression of PPARg, Bcl-2, and Bax and the activity of JAK2 and STAT3 were also investigated by Western blot assay. RESULTS We found that rosiglitazone significantly inhibited LPS-induced cell apoptosis, ROS production, and inflammation in HUVECs. Furthermore, we found a significant reduction of JAK2/STAT3 activation and the Bax/Bcl-2 ratio in LPS-induced HUVECs response to rosiglitazone treatment. CONCLUSIONS Treatment with rosiglitazone can reduce apoptosis and inflammation in HUVECs induced by LPS.

[Downregulation of MCL-1 by Diallyl Disulfide Induces G2/M Arrest in Human Leukemia K562 Cells and Its Mechanism].

OBJECTIVE: To investigate the inducing effect of down-regulation of MCL-1 by diallyl disulfide(DADS) on the G2/M arrest of human leukemia K562 cells and its mechanisms. METHODS: CCK-8 was used to detect the effect of DADS on proliferation of K562 cells, flow cytometry was employed to observe the effect of cycle arrest by DADS and RNAi silencing MCL-1 gene in K562 cells. The expressions of MCL-1, PCNA and CDK1 in K562 cells treated with DADS were detected by Western blot. The amphigamy of MCL-1 with PCNA and CDK1 was detected by Coimmunoprecipitation. RESULTS: CCK-8 detection showed that the inhibition rates of K562 cells treated with 15, 30, 60, 120, 240 µmol/L DADS were 32.48%, 59.34%, 66.42%, 77.06%, 81.05% respectively (P<0.05). Flow cytometry analysis revealed that the perecentages of G2/M cells were increased to 18.6% and 34.4%, 17.5% and 28.5%, respectively at 24 and 48 h after treating K562 cells with 60 and 120 µmol/L DADS (P<0.05). And the perecentage of G2/M cells of silencing MCL-1 was significantly increased (P<0.05). Silencing effects of MCL-1+DADS on the cells were enhanced more significantly as compared with DADS or MCL-1 alone (P<0.05). Western blot exhibited that DADS could markedly downregulate the expression of MCL-1, PCNA and CDK1(P<0.05). Coimmunoprecipitation revealed that MCL-1 bound with PCNA and CDK1, then forming heterodimers, which were downregulated respectively more significantly than that in the control group after treating K562 cells with DADS for 8 h (P<0.05). CONCLUSION: DADS can inhibit the K562 cell proliferation and induce them arrest G2/M through downregulation of MCL-1, then decreasing the expression of PCNA and CDK1 in hunan leukemia K562 cells. Moreover, silencing MCL-1 can enhance the effect of DADS.

Identification of potential targets for differentiation in human leukemia cells induced by diallyl disulfide.

Diallyl disulfide (DADS) is a primary component of garlic, which has chemopreventive potential. We previously found that moderate doses (15-120 µM) of DADS induced apoptosis and G2/M phase cell cycle arrest. In this study, we observed the effect of low doses (8 µM) of DADS on human leukemia HL-60 cells. We found that DADS could inhibit proliferation, migration and invasion in HL-60 cells, and arrested cells at G0/G1 stage. Then, cell differentiation was displayed by morphologic observation, NBT reduction activity and CD11b evaluation of cytometric flow. It showed that DADS induced differentiation, reduced the ability of NBT and increased CD11b expression. Likewise, DADS inhibited xenograft tumor growth and induced differentiation in vivo. In order to make sure how DADS induced differentiation, we compared the protein expression profile of DADS-treated cells with that of untreated control. Using high resolution mass spectrometry, we identified 18 differentially expressed proteins after treatment with DADS, including four upregulated and 14 downregulated proteins. RT-PCR and western blot assay showed that DJ-1, cofilin 1, RhoGDP dissociation inhibitor 2 (RhoGDI2), Calreticulin (CTR) and PCNA were decreased by DADS. These data suggest that the effects of DADS on leukemia may be due to multiple targets for intervention.

A label-free electrochemical aptasensor for the analysis of the potassium ion.

Herein, a simple and novel electrochemical method for the detection of potassium ions (K(+)) was developed. In the presence of potassium ions, the potassium ions aptamer will form a G-quadruplex complex. Thus, further addition of hemin in the presence of potassium ions will lead to the formation of a recombined G-quadruplex. Then the electroactive label, hemin, will give an electrochemical response. The linear range of the method covered a large variation of K(+) concentration from 0.1 nM to 0.1 µ M and the detection limit of 0.1 nM was obtained. Moreover, this assay was able to detect K(+) with high selectivity and had great potential applications.

Paeoniflorin attenuates Aß25-35-induced neurotoxicity in PC12 cells by preventing mitochondrial dysfunction.

The pathogenic mechanism of neurodegenerative brain disorder such as Alzheimer's disease (AD) has been still far from clearly understood. Previous research has identified that mitochondrial dysfunction induced by Aß has been recognized as a hallmark in AD. Therefore, the effective agents targeting ß-amyloid (Aß)-induced mitochondrial dysfunction may be useful for the treatment or prevention of AD. In the present study, the neuroprotective effect of paeoniflorin (PF), one monoterpene glycoside isolated from the Chinese herb Radix Paeoniae alba, on Aß25-35-induced toxicity in PC12 cells was investigated for the first time. The results showed that PF could attenuate or restore the cell injury induced by Aß25-35 in PC12 cells through preventing mitochondrial dysfunction, including decreased mitochondrial membrane potential, increased cytochrome c release as well as activity of caspase-3 and caspase-9. Therefore, our data provide the evidence that PF could protect PC12 cells against Aß25-35-induced neurotoxicity and might be a potentially therapeutic approach for AD in the future.

Mathematical modeling of therapeutic strategies for myeloid malignancies.

The existence of malignant stem cells has been proven for hematopoietic disorder as well as some solid tumors. Although significant improvements in cancer therapy have been made, tumor recurrence is frequent and can partly be due to the absence of therapeutic target which tumor stem cells are regarded as. In this paper we shall explore different therapeutic scenarios for successful tumor treatment by using a predictive mathematical model based on the cell compartment method. In particular, we shall study the effects of the chemotherapeutic target rate and of the interval of G-CSF administration on therapy for myeloid malignancies through simulating chemotherapy with G-CSF (granulocyte colony-stimulating factor) support. The results indicate that if target rate is raised to an enough high value, the efficiency of chemotherapy increases so greatly that the tumor mature cells perish completely and normal mature cells are maintained at a normal level. Furthermore, the administration of G-CSF can increase the amount of the normal mature cells to a normal level. However, too long interval of G-CSF administration is demonstrated not propitious to patients' healing. These results indicate that the simulations may be an effective approach to help designing therapeutic scenarios for successful tumor treatment by chemotherapy.

Involvement of Mcl1 in diallyl disulfide-induced G2/M cell cycle arrest in HL-60 cells.

Diallyl disulfide (DADS) has shown potential as a therapeutic agent in various cancers. Previously, we found that myeloid cell leukemia sequence 1 (Mcl1) was downregulated in DADS-induced cell cycle arrest in HL-60 human leukemia cells. Here, we investigated the role of this protein in DADS-induced G2/M cell cycle arrest in HL-60 cells. We demonstrated that DADS treatment significantly increased the proportion of G2/M phase HL-60 cells (P<0.05) and caused a time-dependent significant downregulation of Mcl1 and the cell cycle-related proteins PCNA and CDK1 (P<0.05). Small interfering RNA-mediated knockdown of Mcl1 expression in HL-60 cells arrested the cell cycle in G2/M phase. By co-immunoprecipitation, we demonstrated that Mcl1 associated with PCNA and CDK1 in G2/M cell cycle arrest in DADS-treated HL-60 cells. DADS decreased the interaction of Mcl1 with PCNA and CDK1, leading to G2/M cell cycle arrest in HL-60 cells. Mcl1 plays an important role in DADS-induced G2/M cell cycle arrest in HL-60 human leukemia cells.