Predictive value of preoperative serum CCL2, CCL18, and VEGF for the patients with gastric cancer

Background

To investigate the expression of chemokine ligand 2 (CCL2), chemokine ligand 18 (CCL18), and vascular endothelial growth factor (VEGF) in peripheral blood of patients with gastric cancer and their correlation with presence of malignancy and disease progression.

Methods

Sixty patients with pathological proved gastric cancer were prospectively included into study. The levels of CCL2, CCL18, and VEGF in peripheral blood were examined by enzyme-linked immunosorbentassay (ELISA). Peripheral blood from 20 healthy people was examined as control.

Results

The preoperative serum levels of CCL2, CCL18 and VEGF in gastric cancer patients were significantly higher than that of controls (P <0.001, P <0.001, and P <0.001, respectively). ROC curve analysis showed that with a cut-off value of ≥1272.8, the VEGF*CCL2 predicted the presence of gastric cancer with 83% sensitivity and 80% specificity. Preoperative serum CCL2 was significantly correlated to N stage (P =0.040); CCL18 associated with N stage (P =0.002), and TNM stage (P =0.002); VEGF correlated to T stage (P =0.000), N stage (P =0.015), and TNM stage (P =0.000).

Conclusion

Preoperative serum levels of CCL2 and VEGF could play a crucial role in predicting the presence and progression of gastric cancer.

     

<Emphasis Type="Italic">Helicobacter bilis</Emphasis>-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

?

Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.

Purpose

We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.

Methods

16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.

Results

Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.

Conclusion

In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.

     

Role of topoisomerase mutations,plasmid mediated resistance (<Emphasis Type="Italic">qnr</Emphasis>) and acrAB efflux pump in fluoroquinolone resistant clinical isolates of avian <Emphasis Type="Italic">Escherichia coli</Emphasis>

Introduction

We investigated the role of topoisomerase mutations, increased level of the multidrug efflux pump AcrAB, and the plasmid-borne genes (qnr) in the fluoroquinolone (FQ) resistant avian Escherichia coli simultaneously.

Material and method

Here, we used four FQs (ciprofloxacin, enrofloxacin, ofloxacin and pefloxacin) and eight clinical isolates of E. coli containing six fluoroquinolone-resistant and two fluoroquinolone- susceptible. PCR and direct sequencing methods were used to detect the role of regulator/ repressor gene (acrR).

Objective

The objective of this study was to determine the relationship of these resistance mechanisms for fluoroquinolone resistance.

Result

The results showed that (i) all four fluoroquinolone- resistant isolates have topoisomerase mutation and plasmid borne genes qnrS and aac(6')-Ib; (ii) three FQ (enrofloxacin, ofloxacin and pefloxacin) resistant isolates harboring qnrS genes; (iii) two FQ (ciprofloxacin and pefloxacin) resistant isolates had topoisomerase mutation and plasmid borne gene qnrS; (iv) all fluoroquinolone susceptible were not harboring qnrS gene and topoisomerase mutation (v) All isolates were negative for qnrA and qnrB.

Conclusion

We found that FQs resistance combination was correlated with synergistically contribution of these resistance mechanisms. Plasmid mediated resistance by qnrS was correlated to pefloxacin resistance but did not correlate to ofloxacin, enrofloxacin and ciprofloxacin. This mechanism might be account for the pefloxacin resistance in avian E. coli.

     

Pam2CSK4 and Pam3CSK4 induce iNOS expression via TBK1 and MyD88 molecules in mouse macrophage cell line RAW264.7

Objective

The aim of this study was to investigate the involvement of TLR adaptor molecules, such as TRIF, MyD88, and TBK1 in the induction of iNOS and nitric oxide (NO) production in Pam2CSK4 and Pam3CSK4-treated mouse macrophages.

Method

Mouse macrophage cell line (RAW264.7) was transfected with trif, myd88, and tbk1 siRNAs before stimulated with Pam2CSK4 and Pam3CSK4. The iNOS gene and protein expression were determined by RT-PCR and immunoblotting, respectively. The NO production was determined by Griess reaction assay.

Results

The results showed that the induction of iNOS expression and NO production by Pam2CSK4 and Pam3CSK4 were diminished in tbk1 and myd88-depleted mouse macrophages but not trif-depleted cells.

Conclusion

These results suggested that the TBK1 and MyD88 molecules were essential for the induction of iNOS expression and NO production by both Pam2CSK4 and Pam3CSK4 via TLR2 signaling.

     

The host control of a clinical isolate strain of <Emphasis Type="Italic">P. aeruginosa</Emphasis> infection is independent of Nod-1 but depends on MyD88

Objective and design

The objective of this study was to investigate the role of Nod1 in the recruitment of neutrophils into the infection site and in the establishment of the inflammatory response elicited by a clinical isolate strain of P. aeruginosa in vivo, while comparing it to the well-established role of MyD88 in this process.

Subjects

Wild-type, Nod1^?/? and MyD88^?/? mice, all with a C57Bl/6 background.

Methods

Mice were intranasally infected with Pseudomonas aeruginosa DZ605. Bronchoalveolar lavage and blood were harvested 6 or 20 h post-infection for evaluating bacterial load, chemokine levels and neutrophil migration. Survival post-infection was also observed.

Results

We show here that wild-type and Nod1^?/? mice induce similar lung chemokine levels, neutrophil recruitment, and bacterial load, thus leading to equal survival rates upon P. aeruginosa pulmonary infection. Furthermore, we confirmed the essential role of MyD88-dependent signalling in recruiting neutrophils and controlling P. aeruginosa-induced pulmonary infection.

Conclusion

The results suggest that in contrast to MyD88, under our experimental conditions, the absence of Nod1 does not impair the recruitment of neutrophils in response to P. aeruginosa DZ605.

     

The alpha-lipoic acid derivative DHLHZn: a new therapeutic agent for acute lung injury in vivo

Objective and design

An animal experiment was performed to demonstrate the anti-inflammatory effects of an alpha-lipoic acid (ALA) derivative, dihydrolipoyl histidinate zinc complex (DHLHZn) for acute lung injury (ALI) and to investigate the mechanism of action.

Material

Rats were randomly divided into three experimental groups: control group (n = 17), DHLHZn(?) group (n = 11, ALI model rats), and DHLHZn(+) group (n = 12, ALI model rats treated by DHLHZn).

Treatment

Lipopolysaccharides (LPS, 10 mg/kg) were administered intratracheally in the DHLHZn(?) group and the DHLHZn(+) group. For the DHLHZn(+) group, DHLHZn (100 mg/kg) was administered intraperitoneally 2 h prior to LPS administration.

Methods

Four hours after LPS administration, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings were analyzed using the Mann–Whitney U test.

Results

Total number of cells, number of neutrophils and lymphocytes, levels of various inflammatory cytokines, and NF-kB p65 concentration of BALF were significantly lower in the DHLHZn(+) group than in the DHLHZn(?) group (p < 0.05). ALI pathology scores were significantly lower in the DHLHZn(+) group than in the DHLHZn(?) group (p < 0.001).

Conclusions

Anti-inflammatory effects of DHLHZn for ALI were demonstrated by BALF and histopathological findings. The mechanism of action of DHLHZn was considered to be via inhibition of the NF-kB signaling pathway. DHLHZn is thus suggested to be a new prophylactic agent for ALI.

     

LncRNA MEG3 impacts proliferation,invasion, and migration of ovarian cancer cells through regulating <Emphasis Type="Italic">PTEN</Emphasis>

Objective and design

We investigated the expressions of lncRNA MEG3 and PTEN in ovarian cancer tissues and their effects on cell proliferation, cycle and apoptosis of ovarian cancer.

Methods

Expression levels of MEG3 in ovarian cancer cell lines and normal ovarian cell lines were detected by qRT-PCR. Cell viability was detected by MTT assay. Cell apoptosis and cell cycle distribution were measured by flow cytometry. Cell invasion capability was tested by transwell assay. Cell migration capacity was tested by wound healing. The xenograft model was constructed to explore the effect of lncRNA MEG3 on ovarian cancer in vivo.

Result

Compared with normal ovarian cells, expression levels of MEG3 and PTEN were relatively lower in ovarian cancer cells. There was a positive correlation between the expression of PTEN and the expression of MEG3. Enhanced expression level of PTEN suppressed SKOV3 cell proliferation, increased cell apoptosis rate, and decreased cell invasion and migration.

Conclusion

LncRNA MEG3 and PTEN were down-regulated in ovarian cancer cells. LncRNA MEG3 regulated the downstream gene PTEN in ovarian cancer cells to prohibit cell proliferation, promote apoptosis and block cell cycle progression.

     

Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients

Objective

In the present study, we analyzed the possible association of inflammasome gene variants and expression to rheumatoid arthritis (RA)’s development and severity in the Brazilian population.

Materials and methods

Thirteen single nucleotide polymorphisms within six inflammasome genes (NLRP1, NLRP3, NLRC4, AIM2, CARD8, CASP1) as well as IL1B and IL18 genes in two different Brazilian populations (from Northeast and Southeast Brazil) were analyzed. We also evaluated inflammasome gene expression profile in resting and LPS?+?ATP-treated monocytes from RA patients and healthy individuals. For genetic association study, 218 patients and 307 healthy controls were genotyped. For gene expression study, inflammasome genes mRNA levels of 12 patients and ten healthy individuals were assessed by qPCR.

Results

Our results showed that rs10754558 NLRP3 and rs2043211 CARD8 polymorphisms are associated with RA development (p value?=?0.044, OR?=?1.77, statistical power?=?0.999) and severity measured by Health Assessment Questionnaire (HAQ) (p value?=?0.03), respectively. Gene expression analyses showed that RA patients display activation of CASP1, IL1B and IL1R genes independently of LPS + ATP activation. In LPS?+?ATP-treated monocytes, NLRP3 and NLRC4 expressions were also significantly higher in patients compared with controls.

Conclusions

The first reported results in Brazilian populations support the role of inflammasome in the development of RA.

     

Interleukin 18 Promoter Variants (−137G>C and −607C>A) in Patients with Chronic Hepatitis C: Association with Treatment Response

Background

Recently, two functional IL18 promoter variants, ?607C>A (rs1946518) and ?137G>C (rs187238), were associated with viral clearance in patients with hepatitis C. The present study focused on their relevance for treatment response.

Methods

Seven hundred fifty-seven chronically infected European patients and 791 controls were enrolled in the study. IL18 genotyping was performed by allele-specific PCR. Liver histology was available in 67.9%.

Results

Genotype and allele frequencies were equally distributed in patients and controls. No significant association with various disease characteristics was observed. However, when comparing patients with sustained virological response (SR) and non-SR, statistically significant associations were found for both variants (p?=?0.0416 and p?=?0.0274, respectively). In viral genotype 1, the ?607A allele was positively associated with treatment response (p?=?0.0190; OR 1.537; 95% CI, 1.072–2.205) and the ?137G allele with a higher rate of nonresponse (p?=?0.0302; OR 1.524; 95% CI, 1.040–2.233).

Conclusions

The association of IL18 variants with treatment response in genotype 1 hepatitis C patients implies a predictive and modifying role of these genetic variants.

     

Are non-pylori helicobacters present in the human oral cavity?

Introduction and objective

Helicobacter pylori (H. pylori) is a human gastric pathogen. Because of presence of H. pylori oral cavity, there is a possibility of H. pylori transmission by oral-oral route. In a crosssectional study, the presence of some virulence factors of H. pylori and also non-pylori Helicobacters in dental plaque samples of participants was investigated.

Methods

The samples were collected from at least two teeth surfaces. DNA of the samples was extracted using specific kit. The presence of dupA (jhp0917 and jhp0918) and babA2 genes and also Helicobacter genus and H. pylori species was investigated using polymerase chain reaction by specific primers.

Results

In total 44% (20/45) and 86.7% (39/45) of samples was positive for ureC and 16SrRNA genes respectively. The frequency of babA2, jhp0917 and jhp0918 genes in H. pylori isolates were 40, 20 and 65% respectively. It seems 19 samples were positive probably non-pylori Helicobacters.

Conclusion

In the present study we report for the first time the presence of non-pylori Helicobacter species and also high frequency of babA2 and dupA genotypes in dental plaque samples.

     

Headache-Specific Locus of Control and Migraine-Related Quality of Life: Understanding the Role of Anxiety

Purpose

This cross-sectional study examined the relationship between headache-specific locus of control (HSLC) and migraine-related quality of life, and anxiety as a mediator of this relationship.

Method

Two hundred and thirty-two people with migraine participated in the treatment of severe migraine trial. At baseline, participants completed self-report questionnaires of headache-specific locus of control (HSLC; subscales?=?internal, chance, and medical professionals), anxiety, and migraine-related quality of life. Correlations examined relationships between HSLC, anxiety, and migraine-related quality of life; ordinary least squares regression evaluated anxiety as a mediator of the relationship between HSLC and migraine-related quality of life.

Results

Higher internal HSLC was related to higher overall migraine-related quality of life (ps?<?.05) and emotion function impairments (p?=?.012). Anxiety mediated the relationship between internal HSLC and all measures of migraine-specific quality of life (ps?<?.05). Higher external (medical professionals and chance) HSLC was related to higher migraine-related quality of life impairments (all ps?<?.001).

Conclusion

All HSLC beliefs are associated with higher migraine-related quality of life impairments. Anxiety mediates the relationship between internal HSLC and migraine-related quality of life.

     

Predicting the potential global distribution of diosgenin-contained <Emphasis Type="Italic">Dioscorea</Emphasis> species

Background

Diosgenin, mainly extracted from wild diosgenin-contained Dioscorea species, is a well-known starting material of steroidal and contraceptive drugs. However, due to large market demand and increasingly ecological damage, wild Dioscorea species resources available have been gradually declining. Therefore, identification of new potential ecological distribution of diosgenin-contained Dioscorea species is necessary for diosgenin production.

Methods

In this study, a large occurrence dataset (1808 data points) of diosgenin-contained Dioscorea species was obtained from Eastern Asia, Southern North America and Southern Africa. Along with the data for six critical environmental parameters and one soil factor, Geographic Information System for Global Medicinal Plant was applied to predict the potential suitable distribution of Dioscorea species.

Results

The results showed that the potential distribution of these Dioscorea species covered a wide field, and that new ecological suitability areas were mainly distributed in the central region of South America, the southern part of the European and coastal region of Oceania. Jackknife test indicated that annual precipitation and annual mean radiation were the important climatic factors controlling the distribution of Dioscorea species.

Conclusions

The suitable areas and critical climatic factors will serve as a useful guide for diosgenin-contained Dioscorea species conservation and cultivation in ecological suitable areas.

     

Larger and More Prominent Graphic Health Warnings on Plain-Packaged Tobacco Products and Avoidant Responses in Current Smokers: a Qualitative Study

Background

The introduction of tobacco plain packaging legislation in Australia meant that all tobacco products were to be sold in plain dark-brown packaging with 75 % front-of-pack graphic health warnings and standardised font type and size for brand name and product variant. The change in the size and prominence of the warnings has been proposed as a reason for behaviour change in smokers in terms of increased intentions to quit and quit attempts.

Purpose

The current research examined attitudes and beliefs of cigarette smokers toward the increased size and prominence of the warnings and effects on their behaviour.

Method

Participants (N?=?160) completed open-ended responses to questions on beliefs, attitudes and responses to plain packaging. Responses were subjected to inductive thematic content analysis for key themes.

Results

Four themes emerged from the analysis: emotional response to packaging, scepticism of health warnings, warnings and cessation behaviour, and avoidant coping behaviours. Participants reported increased negative emotional responses to the packaging and made specific reference to the graphic health warnings. Some participants attempted to discredit the messages. Others reported increased intentions to quit or quitting attempts. There were pervasive reports of avoidant responses including covering or hiding the warnings.

Conclusion

Consistent with theories of illness perceptions and coping, current findings indicate that the larger, prominent graphic health warnings on plain-packaged tobacco products had pervasive effects on threat perceptions and subsequent behavioural responses. While some of the reported responses were adaptive (e.g. attempts to quit), others were maladaptive (e.g. avoiding the warnings).

     

Antimicrobial activity of HL-60 cells compared to primary blood-derived neutrophils against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

Background

The human leukemia cell line HL-60 is considered an alternative cell culture model to study neutrophil differentiation and migration. The aim of this study was to characterize the suitability of HL-60 cells differentiated to neutrophil-like cells (nHL-60) as substitute for blood-derived human neutrophils to investigate the interaction of neutrophils with Staphylococcus aureus.

Methods

For this purpose, antimicrobial activity, bacterial uptake, production of reactive oxygen species and the release of neutrophil extracellular traps (NETs) by nHL-60 cells were analyzed and compared to primary blood-derived neutrophils using Staphylococcus aureus as important human and animal pathogen.

Results

Overall, the antimicrobial activities of nHL-60 cells were distinctly lower compared to blood-derived neutrophils. Furthermore, production of reactive oxygen species as well as NET formation was clearly impaired in nHL-60 cells.

Conclusion

This study indicates that HL-60 cells are of limited usage as an alternative model to study antimicrobial functions of neutrophils against Staphylococcus aureus.

     

Passive administration of purified secretory IgA from human colostrum induces protection against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> in a murine model of progressive pulmonary infection

Background

Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections.

Materials and methods

Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated.

Results

The passive administration of hsIgA reduces the pneumonic area before challenge with M. tuberculosis. The intratracheal administration of M. tuberculosis preincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury.

Conclusions

HsIgA purified from colostrum protects against M. tuberculosis infection in an experimental mouse model.

     

Association of hyperhomocysteinemia with genetic variants in key enzymes of homocysteine metabolism and methotrexate toxicity in rheumatoid arthritis patients

Objectives

The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients.

Methods

A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy?>?15 µmol/L.

Results

MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07–4.57]; p?=?0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p?=?0.035).

Conclusions

The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.

     

Inflammatory protein response in <Emphasis Type="Italic">CDKL5</Emphasis>-Rett syndrome: evidence of a subclinical smouldering inflammation

Background

Mutations in the cyclin-dependent kinase-like 5 gene cause a clinical variant of Rett syndrome (CDKL5-RTT). A role for the acute-phase response (APR) is emerging in typical RTT caused by methyl-CpG-binding protein 2 gene mutations (MECP2-RTT). No information is, to date, available on the inflammatory protein response in CDKL5-RTT. We evaluated, for the first time, the APR protein response in CDKL5-RTT.

Methods

Protein patterns in albumin- and IgG-depleted plasma proteome from CDKL5-RTT patients were evaluated by two-dimensional gel electrophoresis/mass spectrometry. The resulting data were related to circulating cytokines and compared to healthy controls or MECP2-RTT patients. The effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) were evaluated.

Results

CDKL5-RTT mutations resulted in a subclinical attenuated inflammation, specifically characterized by an overexpression of the complement component C3 and CD5 antigen-like, both strictly related to the inflammatory response. Cytokine dysregulation featuring a bulk increase of anti-inflammatory cytokines, predominantly IL-10, could explain the unchanged erythrocyte sedimentation rate and atypical features of inflammation in CDKL5-RTT. Omega-3 PUFAs were able to counterbalance the pro-inflammatory status.

Conclusion

For the first time, we revealed a subclinical smouldering inflammation pattern in CDKL5-RTT consisting in the coexistence of an atypical APR coupled with a dysregulated cytokine response.

     

The Association of Sensory Responsiveness with Somatic Symptoms and Illness Anxiety

Background

Somatoform Disorders or Somatic Symptom and Related Disorders are a major public health problem.The pathophysiology underlying these disorders is not yet understood.

Purpose

The aim of this study was to explore if sensory responsiveness could contribute to a better understanding of pathophysiological mechanisms underlying two key symptoms of Somatoform Disorders, namely somatic symptoms and illness anxiety.

Methods

We measured vibrotactile perception thresholds with the HVLab Perception Meter and examined their association with somatic symptoms, illness anxiety and trait anxiety. A sample of 205 volunteers participated in the study.

Results

Sensory responsiveness was neither associated with somatic symptoms (β?=??0.01; 95 % confidence interval (CI), ?0.37, 0.39) nor trait anxiety (β?=??0.07; 95 % CI, ?0.30, 0.07). However, lower vibrotactile perception thresholds were associated with increased scores of the overall illness anxiety scale (β?=??0.65; 95 % CI, ?1.21, ?0.14) and its constituent subscale disease conviction (β?=??2.07; 95 % CI, ?3.94, ?0.43).

Conclusions

Our results suggest that increased sensory responsiveness is associated with illness anxiety and hence should be examined further as potential target within the etiopathology of somatoform disorders.