Esophageal cancer remains the sixth leading cause of cancer associated death and eighth most common cancer worldwide. Genetic factors, such as single nucleotide polymorphisms (SNPs), may contribute to the carcinogenesis of esophageal cancer. Here, we conducted a hospital based case-control study to evaluate the genetic susceptibility of functional SNPs on the development of esophageal cancer. A total of 629 esophageal squamous cell carcinoma (ESCC) cases and 686 controls were enrolled for this study. The OPG rs3102735 T>C, rs2073618 G>C, RANK rs1805034 T>C, RANKL rs9533156 T>C and rs2277438 A>G were determined by ligation detection reaction method. Our findings suggested that RANK rs1805034 T>C is associated with the susceptibility of ESCC, which is more evident in male and elder (≥63) patients. Our study provides the first evidence that functional polymorphisms RANK rs1805034 T>C may be an indicator for individual susceptibility to ESCC. However, further larger studies among different ethnic populations are warranted to verify our conclusion.
Although the International Agency for Research on Cancer (IARC) has classified various indoor air pollutants as carcinogenic to humans, few studies evaluated the role of household ventilation in reducing the impact of indoor air pollutants on lung cancer risk.
To explore the association between household ventilation and lung cancer.
A population-based case-control study was conducted in a Chinese population from 2003 to 2010. Epidemiologic and household ventilation data were collected using a standardized questionnaire. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORadj) and their 95% confidence intervals (CI).
Among 1,424 lung cancer cases and 4,543 healthy controls, inverse associations were observed for good ventilation in the kitchen (ORadj = 0.86, 95% CI: 0.75, 0.98), bedroom (ORadj = 0.90, 95% CI: 0.79, 1.03), and both kitchen and bedroom (ORadj = 0.87, 95% CI: 0.75, 1.00). Stratified analyses showed lung cancer inversely associated with good ventilation among active smokers (ORadj = 0.85, 95% CI: 0.72, 1.00), secondhand smokers at home (ORadj = 0.77, 95% CI: 0.63, 0.94), and those exposed to high-temperature cooking oil fumes (ORadj = 0.82, 95% CI: 0.68, 0.99). Additive interactions were found between household ventilation and secondhand smoke at home as well as number of household pollutant sources.
A protective association was observed between good ventilation of households and lung cancer, most likely through the reduction of exposure to indoor air pollutants, indicating ventilation may serve as one of the preventive measures for lung cancer, in addition to tobacco cessation.
Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90 percent of esophageal cancers. Genetic factors probably play an important role in the ESCC carcinogenesis.
We conducted a hospital based case-control study to evaluate functional hTERT rs2736098 G>A and TERT-CLPTM1L rs401681 C>T single nucleotide polymorphisms (SNPs) on the risk of ESCC. Six hundred and twenty-nine ESCC cases and 686 controls were recruited. Their genotypes were determined using the ligation detection reaction (LDR) method.
When the TERT-CLPTM1L rs401681 CC homozygote genotype was used as the reference group, the CT genotype was associated with a significantly decreased risk of ESCC (adjusted OR = 0.74, 95% CI = 0.58–0.94, p = 0.012); the CT/TT variants were associated with a 26% decreased risk of ESCC (adjusted OR = 0.74, 95% CI = 0.59–0.93, P = 0.009). The significantly decreased risk of ESCC associated with the TERT-CLPTM1L rs401681 C>T polymorphism was associated with male sex, young age (<63 years in our study) and alcohol consumption. No association between the hTERT rs2736098 G>A polymorphism and ESCC risk was observed.
TERT-CLPTM1L rs401681 CT and CT/TT genotypes were associated with decreased risk of ESCC, particularly among men, young patients and those reported to be drinkers. However, our results are preliminary conclusions. Larger studies with more rigorous study designs are required to confirm the current findings.
Fargesia decurvata is closely allied with F. dracocephala and differs in 5 major characters (i.e. the culm sheath blade base shape, the width of the culm sheath blade base, the auricle shape, and the lower surface of leaf blade) in Fargesia. It is difficult to distinguish these two species because of existing of transitional statements of characters. The aims of this paper are to (i) investigate whether the variation of the characters is continuous or not; (ii) reveal whether the publishment of F. dracocephala was the result of discontinuous sampling of F. decurvata or not.
Ten populations of F. decurvata and F. dracocephala were investigated in their entire distribution (including type localities). The statements of 5 major characters were measured from 693 annual and 693 perennial culms of 231 individuals in 10 populations, and analyzed at population, individual and culm levels. UPGMA cluster analysis was carried out based on 29 characters from 10 populations of F. decurvata and F. dracocephala and 2 populations of F. qinlingensis as outgroup. The ITS sequences were also sequenced and analyzed.
Five major characters exhibited great variation not only at population level, but at individual level within a population, even the culm level within an individual and in different parts of the same culm. Cluster analyses showed that 10 populations of F. decurvata and F. dracocephala were not divided into two species, but they were well separated with outgroup. There was no difference in floral organ between F. decurvata and F. dracocephala. MP and NJ trees based on ITS sequences showed the same results with the cluster analysis on morphological characters. All the facts indicated that the publishment of F. dracocephala was the result of discontinuous sampling of F. decurvata, and F. dracocephala should be treated as the synonym of F. decurvata.
Protective effect of garlic on the development of cancer has been reported in vitro and in vivo experimental studies, however, few human epidemiological studies have evaluated the relationship. A population-based case-control study has been conducted in a Chinese population from 2003 to 2010, with the aim to explore the association between raw garlic consumption and lung cancer. Epidemiological data were collected by face-to-face interviews using a standard questionnaire among 1,424 lung cancer cases and 4,543 healthy controls. Unconditional logistic regression was employed to estimate adjusted odds ratios (OR) and their 95% confidence intervals (CIs), and to evaluate ratio of odds ratios (ROR) for multiplicative interactions between raw garlic consumption and other risk factors. After adjusting for potential confounding factors, raw garlic consumption of ≥ 2 times per week is inversely associated with lung cancer (OR = 0.56, 95% CI = 0.44-0.72) with a monotonic dose-response relationship (p for trend <0.001). Furthermore, strong interactions at either additive and/or multiplicative scales were observed between raw garlic consumption and tobacco smoking (Synergy Index (SI) = 0.70, 95% CI = 0.57-0.85; and ROR = 0.78, 95% CI = 0.67-0.90), as well as high-temperature cooking oil fume (ROR = 0.77, 95% CI = 0.59-1.00). In conclusion, protective association between intake of raw garlic and lung cancer has been observed with a dose-response pattern, suggesting that garlic may potentially serve as a chemopreventive agent for lung cancer. Effective components in garlic in lung cancer chemoprevention warrant further in-depth investigation.
lung cancer; garlic consumption; case-control study; China
The miR-29 family have been demonstrated acting as vital tumor suppressor in multiple cancers as well as regulators in the adaptive immune system. Little is known about their role in leukemogenesis. The purpose of this study is to analyze the expression pattern of miR-29a/29b and its target genes Mcl-1 (myeloid cell leukemia sequence 1) and B-cell lymphoma 2 (Bcl-2) in myeloid leukemia.
Quantitative real-time PCR was used for detecting genes expression level in peripheral blood mononuclear cells (PBMCs) from 10 cases with newly diagnosed, untreated acute myeloid leukemia (AML) and 14 cases with newly diagnosed, untreated chronic myeloid leukemia (CML) in chronic phase, and 14 healthy individual (HI) served as controls. Correlation between the relative expression levels of different genes have been analyzed.
Significant lower expression of miR-29a/29b and higher expression level of two potential target genes Bcl-2 and Mcl-1 were found in PBMCs from AML and CML patients compared with HI group. In addtion, miR-29a expression in AML was significantly lower than that in CML. Moreover, negative correlation between miR-29a/29b and its target genes have been found. While, positive correlation between relative expression level of miR-29a and miR-29b or Bcl-2 and Mcl-1 were presented in the total 38 research objects.
Down-regulated miR-29a and miR-29b, and accompanying up-regulated Bcl-2 and Mcl-1 are the common feature in myeloid leukemias. These data further support the role for miR-29a/29b dysregulation in myeloid leukemogenesis and the therapeutic promise of regulating miR-29a/29b expression for myeloid leukemia in the future.
Non-traditional CD4+CD25–CD69+ T cells were found to be involved in disease progression in tumor-bearing mouse models and cancer patients recently. We attempted to define whether this subset of T cells were related to leukemia relapse after allogeneic hematopoietic cell transplantation (allo-HSCT).
The frequency of CD4+CD25–CD69+ T cells among the CD4+ T cell population from the bone marrow of relapsed patients, patients with positive minimal residual disease (MRD+) and healthy donors was examined by flow cytometry. The CD4+CD25-CD69+ T cells were also stained with the intracellular markers to determine the cytokine (TGF-β, IL-2 and IL-10) secretion.
The results showed that the frequency of CD4+CD25–CD69 + T cells was markedly increased in patients in the relapsed group and the MRD + group compared to the healthy donor group. The percentage of this subset of T cells was significantly decreased after effective intervention treatment. We also analyzed the reconstitution of CD4+CD25–CD69+ T cells at various time points after allo-HSCT, and the results showed that this subset of T cells reconstituted rapidly and reached a relatively higher level at +60 d in patients compared to controls. The incidence of either MRD+ or relapse in patients with a high frequency of CD4+CD25-CD69+ T cells (>7%) was significantly higher than that of patients with a low frequency of CD4+CD25-CD69+ T cells at +60 d, +90 d and +270 d after transplant. However, our preliminary data indicated that CD4+CD25-CD69+ T cells may not exert immunoregulatory function via cytokine secretion.
This study provides the first clinical evidence of a correlation between non-traditional CD4+CD25-CD69+ Tregs and leukemia relapse after allo-HSCT and suggests that exploration of new methods of adoptive immunotherapy may be beneficial. Further research related to regulatory mechanism behind this phenomenon would be necessary.
Regulatory T cells; Allogeneic Hematopoietic Stem Cell Transplantation; Relapse; Leukemia; Immunoregulatory
Seed germination is an important event in the life cycle of seed plants, and is controlled by complex and coordinated genetic networks. Many genes involved in the regulation of this process have been identified in different plant species so far. Recent studies in both Arabidopsis and wheat have uncovered a new role of MOTHER OF FT AND TFL1 (MFT) in seed germination. Here, we reported a homolog of MFT in soybean (GmMFT) which strongly expressed in seeds. Detailed expression analysis showed that the mRNA level of GmMFT increased with seed development but declined during seed germination. The transcription of GmMFT also responded to exogenous application of ABA and GA3. Ectopic expression of GmMFT CDS in Arabidopsis moderately inhibited seed germination. All these evidences suggest that GmMFT may be a negative regulator of seed germination.
Acquisition of exogenous genetic material is a key event in bacterial speciation. It seems reasonable to assume that recombination of the incoming DNA into genome would be more efficient with higher levels of relatedness between the DNA donor and recipient. If so, bacterial speciation would be a smooth process, leading to a continuous spectrum of genomic divergence of bacteria, which, however, is not the case as shown by recent findings. The goal of this study was todetermine if DNA transfer efficiency is correlated with the levels of sequence identity.
To compare the relative efficiency of exogenous DNA acquisition among closely related bacteria, we carried out phage-mediated transduction and plasmid-mediated transformation in representative Salmonella strains with different levels of relatedness. We found that the efficiency was remarkably variable even among genetically almost identical bacteria. Although there was a general tendency that more closely related DNA donor-recipient pairs had higher transduction efficiency, transformation efficiency exhibited over a thousand times difference among the closely related Salmonella strains.
DNA acquisition efficiency is greatly variable among bacteria that have as high as over 99% identical genetic background, suggesting that bacterial speciation involves highly complex processes affected not only by whether beneficial exogenous DNA may exist in the environment but also the “readiness” of the bacteria to accept it.
Bacterial speciation; Homologous recombination; Salmonella; Transduction; Transformation
Mitochondria are semi-autonomous organelles regulated by a complex network of proteins that are vital for many cellular functions. Because mitochondrial modulators can impact many aspects of cellular homeostasis, their identification and validation has proven challenging. It requires the measurement of multiple parameters in parallel to understand the exact nature of the changes induced by such compounds. We developed a platform of assays scoring for mitochondrial function in two complementary models systems, mammalian cells and C. elegans. We first optimized cell culture conditions and established the mitochondrial signature of 1,200 FDA-approved drugs in liver cells. Using cell-based and C. elegans assays, we further defined the metabolic effects of two pharmacological classes that emerged from our hit list, i.e. imidazoles and statins. We found that these two drug classes affect respiration through different and cholesterol-independent mechanisms in both models. Our screening strategy enabled us to unequivocally identify compounds that have toxic or beneficial effects on mitochondrial activity. Furthermore, the cross-species approach provided novel mechanistic insight and allowed early validation of hits that act on mitochondrial function.
Trials on sling exercise (SE), commonly performed to manage chronic low back pain (LBP), yield conflicting results. This study aimed to review the effects of SE on chronic LBP.
The randomized controlled trials comparing SE with other treatments or no treatment, published up to August 2013, were identified by electronic searches. Primary outcomes were pain, function, and return to work. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated, using a random-effects model.
Risk of bias was rated as high in 9 included trials, where some important quality components such as blinding were absent and sample sizes were generally small. We found no clinically relevant differences in pain or function between SE and other forms of exercise, traditional Chinese medical therapy, or in addition to acupuncture. Based on two trials, SE was more effective than thermomagnetic therapy at reducing pain (short-term: WMD –13.90, 95% CI –22.19 to –5.62; long-term: WMD –26.20, 95% CI –31.32 to –21.08) and improving function (short-term: WMD –10.54, 95% CI –14.32 to –6.75; long-term: WMD –25.75, 95% CI –30.79 to –20.71). In one trial we found statistically significant differences between SE and physical agents combined with drug therapy (meloxicam combined with eperisone hydrochloride) but of borderline clinical relevance for pain (short-term: WMD –15.00, 95% CI –19.64 to −10.36) and function (short-term: WMD −10.00; 95% CI −13.70 to −6.30). There was substantial heterogeneity among the two trials comparing SE and thermomagnetic therapy; both these trials and the trial comparing SE with physical agents combined with drug therapy had serious methodological limitations.
Based on limited evidence from 2 trials, SE was more effective for LBP than thermomagnetic therapy. Clinically relevant differences in effects between SE and other forms of exercise, physical agents combined with drug therapy, traditional Chinese medical therapy, or in addition to acupuncture could not be found. More high-quality randomized trials on the topic are warranted.
Chronic immune activation is a hallmark of progressive HIV infection and a key determinant of immunodeficiency in HIV-infected individuals. Bacterial lipopolysaccharide (LPS) in the circulation has been implicated as a key factor in HIV infection-related systemic immune activation. We thus investigate the impact of LPS on systemic immune activation in simian immunodeficiency virus (SIV)-infected rhesus macaques of Chinese origin.
The animals were inoculated intravenously with SIVmac239. The levels of plasma viral load and host inflammatory cytokines in PBMC were measured by real-time RT-PCR. CD4/CD8 ratio and systemic immune activation markers were examined by flow cytometric analysis of PBMCs. White blood cell and neutrophil counts and C Reactive Protein levels were determined using biochemistry analyzer. The plasma levels of LPS were determined by Tachypleus Amebocyte Lysate (TAL) test.
The animals inoculated with SIVmac239 became infected as evidenced by the increased plasma levels of SIV RNA and decreased CD4/CD8 ratio. LPS administration of SIV-infected animals induced a transient increase of plasma SIV RNA and immune activation, which was indicated by the elevated expression of the inflammatory cytokines and CD4+HLA-DR+ T cells in PBMCs.
These data support the concept that LPS is a driving factor in systemic immune activation of HIV disease.
The potential impact of transgene escape on the environment and food safety is a major concern to the scientists and public. This work aimed to assess the effect of intein-mediated gene splitting on containment of transgene flow. Two fusion genes, EPSPSn-In and Ic-EPSPSc, were constructed and integrated into N. tabacum, using Agrobacterium tumefaciens-mediated transformation. EPSPSn-In encodes the first 295 aa of the herbicide resistance gene 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) fused with the first 123 aa of the Ssp DnaE intein (In), whereas Ic-EPSPSc encodes the 36 C-terminal aa of the Ssp DnaE intein (Ic) fused to the rest of EPSPS C terminus peptide sequences. Both EPSPSn-In and Ic-EPSPSc constructs were introduced into the same N. tabacum genome by genetic crossing. Hybrids displayed resistance to the herbicide N-(phosphonomethyl)-glycine (glyphosate). Western blot analysis of protein extracts from hybrid plants identified full-length EPSPS. Furthermore, all hybrid seeds germinated and grew normally on glyphosate selective medium. The 6-8 leaf hybrid plants showed tolerance of 2000 ppm glyphosate in field spraying. These results indicated that functional EPSPS protein was reassembled in vivo by intein-mediated trans-splicing in 100% of plants. In order to evaluate the effect of the gene splitting technique for containment of transgene flow, backcrossing experiments were carried out between hybrids, in which the foreign genes EPSPSn-In and Ic-EPSPSc were inserted into different chromosomes, and non-transgenic plants NC89. Among the 2812 backcrossing progeny, about 25% (664 plantlets) displayed glyphosate resistance. These data indicated that transgene flow could be reduced by 75%. Overall, our findings provide a new and highly effective approach for biological containment of transgene flow.
Through the wind velocity and direction monitoring system installed on Jiubao Bridge of Qiantang River, Hangzhou city, Zhejiang province, China, a full range of wind velocity and direction data was collected during typhoon HAIKUI in 2012. Based on these data, it was found that, at higher observed elevation, turbulence intensity is lower, and the variation tendency of longitudinal and lateral turbulence intensities with mean wind speeds is basically the same. Gust factor goes higher with increasing mean wind speed, and the change rate obviously decreases as wind speed goes down and an inconspicuous increase occurs when wind speed is high. The change of peak factor is inconspicuous with increasing time and mean wind speed. The probability density function (PDF) of fluctuating wind speed follows Gaussian distribution. Turbulence integral scale increases with mean wind speed, and its PDF does not follow Gaussian distribution. The power spectrum of observation fluctuating velocity is in accordance with Von Karman spectrum.
The raising unit price of cigarette has been shown to be one of the most effective ways of reducing cigarette consumption and increasing rates of successful quitting. However, researchers have shown that price-sensitive smokers have used a variety of strategies to mitigate the effect of the rising price of cigarettes on their smoking habits. In particular, 23–34% of adult smokers in the US use cheaper brands, and 18–55% use coupons or promotions. Little is known about the discount use by type of brands. As such, the main purpose of this analysis is to evaluate the uses and price discount effects of these price-related discounts by manufacturers and major brands.
An analysis based on the cross-sectional 2009–2010 National Adult Tobacco Survey (NATS).
11 766 current smokers aged 18 or above in the USA.
Primary outcome measures
Price-related discount was defined as smokers who used coupons, rebates, buy-one-get-one-free, two-for-one or any other special promotions for their last cigarettes purchase.
The use of price-related discounts and associated price impact vary widely by cigarette manufacturer and brand. Approximately one of three Camel, one of four Marlboro and one of eight Newport smokers used price-related discounts on their latest cigarette purchases. The average price reductions of discounts offered by Philip Morris (PM) or R.J. Reynolds (RJR) were around 29 cents per pack while that of Lorillard (Newport only) was 24 cents per pack. Cigarette brands that provided significant per pack price reductions include: PM Marlboro (28 cents), RJR brand Camel (41 cents), Doral (50 cents), Kool (73 cents) and Salem (80 cents), and Lorillard Newport (24 cents).
Policies that decrease price-minimisation strategies will benefit public health.
Epidemiology; Health Economics; Public Health
There is limited information about the role of hepatic stellate cells (HSC) in liver innate immunity against hepatitis C virus (HCV). We thus examined whether HSC can produce antiviral factors that inhibit HCV replication in human hepatocytes. HSC expressed functional Toll-like receptor 3 (TLR-3), which could be activated by its ligand, polyinosine-polycytidylic acid (poly I:C), leading to the induction of interferon-γ (IFN-γ) at both mRNA and protein levels. TLR-3 signaling of HSC also induced the expression of IFN regulatory factor 7 (IRF-7), a key regulator of IFN signaling pathway. When HCV JFH-1-infected Huh7 cells were co-cultured with HSC activated with poly I:C or incubated in media conditioned with supernatant (SN) from poly I:C-activated HSC, HCV replication was significantly suppressed. This HSC SN action on HCV inhibition was mediated through IFN-γ, which was evidenced by the observation that antibody to IFN-γ receptors could neutralize the HSC-mediated anti-HCV effect. The role of IFN-γ in HSC-mediated anti-HCV activity is further supported by the observation that HSC SN treatment induced the expression of IRF-7 and IFN stimulated genes (ISGs), OAS-1 and MxA in HCV-infected Huh7 cells. These observations indicate that HSC may be a key regulatory bystander, participating in liver innate immunity against HCV infection using an IFN-γ-dependent mechanism.
Hepatic stellate cells; hepatitis C virus; interferon stimulated genes; interferon-γ; toll like receptor-3
The determination of lot-to-lot consistency in the manufacturing process is a mandatory step in the clinical development of the novel enterovirus 71 (EV71) vaccine. A phase III, randomized, placebo-controlled, double-blind trial assessed the lot consistency, immunogenicity, and safety of the EV71 vaccine in children aged 6 to 59 months. Healthy children (n = 1,400) received one of three lots of the EV71 vaccine containing 400 U of EV71 antigen or a placebo at days 0 and 28. Blood samples were collected before dose 1 and at 28 days after dose 2 (day 56) for an anti-EV71 neutralizing antibody (NTAb) assay. The geometric mean titer (GMT) and the seropositivity rates (with titers of ≥1:8) were compared at day 56. After each dose, the solicited injection site and general adverse events (AEs) were recorded for 7 days, and unsolicited AEs were recorded for 28 days. At day 56, the seropositivity rates ranged from 99.7% to 100% for the vaccine groups. The NTAb GMTs for the vaccine were 140.3 (95% confidence interval [CI], 117.8 to 167.1), 141.5 (95% CI, 118.0 to 169.6), and 146.6 (95% CI, 122.5 to 175.3). The two-sided 95% CI of the log difference in GMTs between the pairs of lots were between −0.176 and 0.176, therefore meeting the predefined equivalence criteria. The percentages of subjects reporting any injection site AEs, general AEs, or serious AEs were similar across the four vaccination groups. In conclusion, the demonstration of consistency between the manufacturing lots confirms for the purposes of clinical development the reliability of the EV71 vaccine production process. (This study has been registered at ClinicalTrials.gov under registration no. NCT01636245.)
Animal models of combined TBI and hemorrhagic shock (HS) suggest a benefit of HBOC-based resuscitation, but their use remains controversial and little is known of the specific effects of TBI and high-pressure (large arterial injury) bleeding on resuscitation. We examine the effect of TBI and aortic tear injury on low volume HBOC resuscitation in a swine polytrauma model and hypothesize that HBOC-based resuscitation will improve survival in the setting of aortic tear regardless of the presence of TBI.
Anesthetized swine subjected to HS with aortic tear +/− fluid percussion TBI underwent equivalent limited resuscitation with HBOC, LR, or HBOC+nitroglycerine (NTG) (vasoattenuated HBOC) and were observed for 6 hours.
There was no independent effect of TBI on survival time after adjustment for fluid type and there was no interaction between TBI and resuscitation fluid type. However, total catheter hemorrhage volume required to reach target shock blood pressure was less with TBI (14.0 ml/kg [12.4, 15.6]) vs. HS-only (21.0 ml/kg [19.5, 22.5]), with equivalent lactate accumulation.
TBI did not affect survival in this polytrauma model, but less hemorrhage was required in the presence of TBI to achieve an equivalent degree of shock suggesting globally impaired cardiovascular response to hemorrhage in the presence of TBI. There was also no benefit of HBOC-based fluid resuscitation over LR, contrary to models using liver injury as the source of hemorrhage. Considering wound location is of paramount importance when choosing resuscitation strategy.
Injection drug use remains a significant risk for acquiring HIV infection. The mechanisms by which morphine enhances HIV infection of human immune cells are largely unknown.
In this study, we sought to determine the possible mechanisms by which morphine upregulates HIV infection of human blood monocyte-derived macrophages (MDM).
In this study, MDM were infected with the R5, X4, and R5X4 HIV strains. HIV replication was determined by performing reverse transcriptase activity assays. HIV receptors were determined by performing reverse transcriptase polymerase chain reactions and flow cytometry assays. β-chemokines were analyzed by performing enzyme-linked immunosorbent assays. In addition, HIV R5 strain and murine leukemia virus envelope-pseudotyped HIV infection was performed to determine whether morphine affects HIV infection of macrophages at entry level.
Morphine significantly enhanced HIV R5 strain infection of MDM but had little effect on X4 strain infection. The macrophage-tropic R5 strain envelope-pseudotyped HIV infection was markedly increased by morphine, whereas murine leukemia virus envelope-pseudotyped HIV infection was not significantly affected. Furthermore, morphine significantly upregulated CCR5 receptor expression and inhibited the endogenous production of β-chemokines in MDM. The opioid receptor antagonist naltrexone blocked the effects of morphine on the production of β-chemokines.
Opiates enhance HIV R5 strain infection of macrophages through the downregulation of β-chemokine production and upregulation of CCR5 receptor expression and may have an important role in HIV immunopathogenesis.
CCR5; β-chemokines; macrophages; morphine; opioid
Perinatal transmission of HIV accounts for almost all new HIV infections in children. There is an increased risk of perinatal transmission of HIV with maternal illicit substance abuse. Little is known about neonatal immune system alteration and subsequent susceptibility to HIV infection after morphine exposure. We investigated the effects of morphine on HIV infection of neonatal monocyte-derived macrophages (MDM). Morphine significantly enhanced HIV infection of neonatal MDM. Morphine-induced HIV replication in neonatal MDM was completely suppressed by naltrexone, the opioid receptor antagonist. Morphine significantly up-regulated CCR5 receptor expression and inhibited the endogenous production of macrophage inflammatory protein-1β in neonatal MDM. Thus, morphine, most likely through alteration of β-chemokines and CCR5 receptor expression, enhances the susceptibility of neonatal MDM to HIV infection, and may have a cofactor role in perinatal HIV transmission and infection.
Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder; abnormal T cell immunity plays a critical role in the development of RA. Recently, A20 was identified as a key negative regulator for T cell activation and inflammatory signaling and may be involved in RA pathogenesis. In this study, we analyzed the expression level of A20, NF-κB, and A20 regulatory factor mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) in patients with RA. Real-time PCR was used to determine the expression level of MALT1, MALT-V1, A20, and NF-κB genes in RA and healthy individuals (HI). Significantly lower A20 expression was found in RA patients compared with those in the healthy group, while NF-κB overexpression could be detected in patients with RA. Moreover, the MALT1 and MALT1-V1 expression level was downregulated in RA patients. A positive correlation between MALT1 and A20 and MALT1-V1 and A20 was found in patients with RA, and a tendency towards a negative correlation was found between MALT1 and NF-κB, MALT1-V1 and NF-κB, and A20 and NF-κB. In conclusion, we first characterized the alternative expression pattern of MALT1, A20, and NF-κB in RA, which may be related to abnormal T cell activation.
SIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial cells. Inhibition of NFAT signaling may be an attractive target to regulate inflammation in atherosclerosis. However, whether NFAT transcriptional activity is suppressed by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT-mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1 suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore, SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that suppression of NFAT transcriptional activity is involved in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Io, and that the negative regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory effects in atherosclerosis.
Behavioral research has demonstrated that males have a higher capability of regulating their own and others' emotions than females; however, little is known about the sex-specific brain mechanisms involved in emotion regulation ability. In the present study, we used voxel-based morphometry to investigate the neural basis underlying emotion regulation ability in a large sample of young adults. Assessment of emotion regulation ability was performed using the Wong and Law Emotional Intelligence Scale. As expected, males significantly scored higher in emotion regulation ability than females did. More importantly, we found the sex differences in the neuroanatomical basis of emotion regulation ability. Males showed a stronger positive relation between emotion regulation ability and regional gray matter volume (rGMV) in the right dorsolateral prefrontal cortex. In contrast, females demonstrated a stronger positive relation between emotion regulation ability and rGMV in an anatomical cluster that extends from the left brainstem to the left hippocampus, the left amygdala and the insular cortex. The present study provides the first empirical evidence regarding the sex-linked neuroanatomical correlates of emotion regulation ability. These findings may help understand why there is a higher prevalence of affective disorders in females and maladaptive behaviors in males.
In the current report a case of a 26-year-old male with a primary dedifferentiated liposarcoma of the femur accompanied by malignant fibrous histiocytoma is presented. The patient complained of a dull intermittent pain, for three months, along the anterolateral aspect of the right knee and was referred to Southwest Hospital (Chongqing, China) in May 2013. All of the radiographic findings, including radiography, magnetic resonance image and emission computed tomography (CT) supported the diagnosis of a primary malignant bone tumor. CT-guided biopsy results demonstrated blood clots and a small quantity of heterogeneous cells. Thus, a limb-salvage procedure, involving a wide resection and total knee endoprosthesis replacement, was performed in May 2012. The final pathological diagnosis was of a primary dedifferentiated liposarcoma of the femur and the dedifferentiated tissue was identified as malignant fibrous histiocytoma. On review of the literature, it was identified that primary intraosseous liposarcoma are a rare and malignant tumor of the skeletal system, with only a small number of cases reported in the English literature since 1980. To the best of our knowledge, a case of dedifferentiated liposarcoma has not previously been reported.
liposarcoma; femur; pathology
It is a common practice for decades to use of sub-therapeutic dose of antibiotics in food-animal feeds to prevent animals from diseases and to improve production performance in modern animal husbandry. In the meantime, concerns over the increasing emergence of antibiotic-resistant bacteria due to the unreasonable use of antibiotics and an appearance of less novelty antibiotics have prompted efforts to develop so-called alternatives to antibiotics. Whether or not the alternatives could really replace antibiotics remains a controversial issue. This review summarizes recent development and perspectives of alternatives to antibiotics. The mechanism of actions, applications, and prospectives of the alternatives such as immunity modulating agents, bacteriophages and their lysins, antimicrobial peptides, pro-, pre-, and synbiotics, plant extracts, inhibitors targeting pathogenicity (bacterial quorum sensing, biofilm, and virulence), and feeding enzymes are thoroughly discussed. Lastly, the feasibility of alternatives to antibiotics is deeply analyzed. It is hard to conclude that the alternatives might substitute antibiotics in veterinary medicine in the foreseeable future. At the present time, prudent use of antibiotics and the establishment of scientific monitoring systems are the best and fastest way to limit the adverse effects of the abuse of antibiotics and to ensure the safety of animal-derived food and environment.
antibiotics; antibiotic alternatives; application; limitation