Expression of paired basic amino acid-cleaving enzyme 4 (PACE4) correlated with prognosis in non-small cell lung cancer (NSCLC) patients

Background

Paired basic amino acid-cleaving enzyme 4 (PACE4) was shown to enhance tumor cells proliferation and invasive. This study provides the first investigation of PACE4 expression in non-small cell lung cancer (NSCLC) and the correlation with clinicopathologic features, prognostic indicators of 172 cases.

Methods

Quantitative real-time PCR (RT-PCR) and immunofluorescence (IF) were applied to detect PACE4 expression in NSCLC and 16HBE cell lines, then 172 consecutive NSCLC and 15 normal lung tissues were studied through immunohistochemistry (IHC). The association between PACE4 expression and clinicopathological parameters was evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of PACE4 expression on survival.

Results

PACE4 expression in NSCLC were significantly higher than normal lung cell and tissues (P<0.05). PACE4 had cytoplasmic expression and was observed in 111 of the 172 (64.5%) NSCLC patients. Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P=0.007), and clinical stage (P=0.024). Multivariable analysis confirmed that PACE4 expression increased the hazard of death after adjusting for other clinicopathological factors [hazards ratio (HR): 1.584; 95% confidence interval (CI): 1.167-2.151; P<0.001]. Overall survival (OS) was significantly prolonged in PACE4 negative group when compared with PACE4 positive group (5-year survival rates, 23.1% vs. 54.5%, log-rank test, χ²=17.717, P<0.001), as was disease-free survival (DFS) (5-year survival rates, 23.4% vs. 55.4%, log-rank test, χ²=20.486, P<0.001).

Conclusions

Our results suggest that positive expression of PACE4 is an independent factor for NSCLC patients and it might serve as a potential prognostic biomarker for patients with NSCLC.     

Differences in distribution and drug sensitivity of pathogens in lower respiratory tract infections between general wards and RICU

Background

Lower respiratory tract infections (LRTIs) are common among patients in hospitals worldwide, especially in patients over the age of 60. This study investigates the differences in distribution and drug sensitivity of pathogens in LRTIs.

Methods

The clinical and laboratory data of 4,762 LRTI patients in the general ward and respiratory intensive care unit (RICU) of Xiangya Hospital (Changsha) were retrospectively analyzed.

Results

The infection rate of Gram-negative bacteria was significantly higher than that of Gram-positive bacteria in both the general ward and RICU (P<0.05). The incidence of Gram-negative bacteria infection was significantly higher in the RICU than in the general ward (P<0.05), whereas the incidence of Gram-positive bacteria infection is less in the RICU than in the general ward (P<0.05). In the general ward, the incidence of Gram-negative bacteria infection significantly increased (P<0.05) over time, whereas the incidence of Gram-positive bacteria infection significantly decreased from 1996 to 2011 (P<0.05). In the RICU, the incidence of Gram-positive bacteria infection decreased, while Gram-negative bacteria infections increased without statistical significance (P>0.05). Staphylococcus pneumoniae and Staphylococcus aureus were found to be the predominant Gram-positive strains in the general ward (34.70-41.18%) and RICU (41.66-54.87%), respectively (P>0.05). Pseudomonas aeruginosa and Acinetobacter baumannii were the predominant gram negative strains in the general ward (19.17-21.09%) and RICU (29.60-33.88%), respectively (P>0.05). Streptococcus pneumoniae is sensitive to most antibiotics with a sensitivity of more than 70%. Staphylococcus aureus is highly sensitive to vancomycin (100%), linezolid (100%), chloramphenicol (74.36-82.19%), doxycycline (69.57-77.33%), and sulfamethoprim (67.83-72.46%); however, its sensitivity to other antibiotics is low and decreased each year. Sensitivity of Pseudomonas aeruginosa to most β-lactam, aminoglycoside, and quinolone group antibiotics decreased each year.

Conclusions

The distribution and drug sensitivity of LRTI pathogens exhibit a high divergence between the general ward and RICU. Streptococcus pneumoniae may not be the predominant pathogen in LRTIs in some areas of China.     

Effect of airway Pseudomonas aeruginosa isolation and infection on steady-state bronchiectasis in Guangzhou,China

Background

Current status of Pseudomonas aeruginosa (PA) infection in clinically stable bronchiectasis in mainland China remains unclear.

Objective

To compare the inflammation and lung function impairment in bronchiectasis patients isolated or infected with PA, potentially pathogenic microorganisms (PPMs) and commensals, and to identify factors associated with PA isolation and infection.

Methods

Patients with steady-state bronchiectasis and healthy subjects were recruited. Peripheral blood and sputum were sampled to determine inflammatory markers and bacterial loads in steady-state bronchiectasis and health. Spirometry and diffusing capacity were also measured.

Results

We enrolled 144 bronchiectasis patients and 23 healthy subjects. PA isolation and infection accounted for 44 and 39 patients, who demonstrated significant inflammatory responses and markedly impaired spirometry, but not diffusing capacity, compared with healthy subjects and patients isolated with other PPMs and commensals (all P<0.05). Except for heightened sputum inflammatory responses, there were no notable differences in serum inflammation and lung function as with the increased density of PA. Female gender [odds ratio (OR): 3.10 for PA isolation; OR: 3.74 for PA infection], 4 or more exacerbations within 2 years (OR: 3.74 for PA isolation, OR: 2.95 for PA infection) and cystic bronchiectasis (OR: 3.63 for PA isolation, OR: 4.47 for PA infection) were the factors consistently associated with PA isolation and infection.

Conclusions

PA elicits intense inflammation and lung function impairment in steady-state bronchiectasis. The density of PA does not correlate with most clinical indices. PA infection is associated with females, frequent exacerbations and cystic bronchiectasis.     

From the Cover: Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity

Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients’ acquisition of chronic P. aeruginosa infections and respiratory virus infection, little is known about the mechanism by which chronic P. aeruginosa infections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondary P. aeruginosa biofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotes P. aeruginosa biofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.Viral–bacterial interactions impact the development and evolution of chronic infections at many mucosal sites, including the airway (1–3). In the lung disease cystic fibrosis (CF), viral infections are linked to pulmonary function decline, antibiotic use, prolonged hospitalizations, and increased respiratory symptoms (4). Respiratory syncytial virus (RSV) is one of the most common viral copathogens in CF and is a culprit in disease progression, promoting early respiratory tract morbidity and reductions in lung function (5, 6). Moreover, beyond the morbidity associated with viral infections alone, RSV has been linked in clinical studies to the development of Pseudomonas aeruginosa coinfections and to the conversion to chronic P. aeruginosa colonization in CF patients (6–10). Although clinical associations between viral infection and the acquisition of colonizing P. aeruginosa are clear, the basic biology of this interaction is not understood.The transition of acute bacterial infections to chronic infections often involves the development of bacterial aggregates, or biofilms. The combination of an up-regulation of antibiotic resistance genes and the production of a polymeric matrix surrounding the biofilm serves to protect bacteria from the hostile environment in the host (11). The development of biofilm in human disease has been studied intensely for its involvement in disease progression in CF. Biofilm development at a mucosal surface requires initial attachment of bacteria to a surface, followed by the formation and growth of microcolonies, resulting in the development of bacterial biofilms, which can undergo regulated dispersal and ultimately seed a new surface (12, 13). Our present understanding of bacterial biofilm development is largely limited to single-organism infections. Although we have long known of polymicrobial communities colonizing human tissues, there is a surprising gap in our understanding of how these communities develop, how they impact human disease, and how host defense mechanisms influence polymicrobial infections. Because our current antimicrobial approaches have limited success for chronic infections, elucidating the mechanism by which biofilms develop during polymicrobial infections may identify new therapeutic targets to combat biofilm persistence.Many environmental cues have been described as contributing to the conversion of P. aeruginosa to a biofilm mode of growth; one such cue is iron. Nutrient iron is tightly regulated in the host through complex interactions among uptake, storage, and use in the cell. Nutritional immunity postulates that, because iron is required for microbial growth, respiration, and metabolism, the host employs many regulatory pathways to sequester free iron (14). In CF, elevated levels of iron in the airways of infected patients are correlated with frequency of exacerbation and have been proposed to play a role in airway colonization (15, 16). The sputum of CF patients contains elevated levels of ferrous iron, and these levels correlate with disease severity (17). Although increased iron in sputum is associated with CF lung disease severity, it still is unknown how iron homeostasis is altered in CF and how this alteration relates to airway infection.Using CF lung disease as a model to understand viral–bacterial interactions at a mucosal surface, we use a coculture system for bacterial biofilm development in association with the airway epithelium. Using RSV, we demonstrate that virus coinfection and the subsequent antiviral IFN response dramatically enhance the growth of P. aeruginosa biofilm in association with the airway epithelium. In addition, we show that virus infection impairs nutritional immunity, allowing the apical release of transferrin and thus increasing bioavailability of iron to promote the growth of P. aeruginosa biofilm. These findings offer new insight into the complex interaction among two pathogens and the host during polymicrobial infections and suggest a mechanism by which nutritional immunity plays a critical role in regulating pathogen persistence in the airway.     

PON2 and ATP2B2 gene polymorphisms with noise-induced hearing loss

Background

Noise-induced hearing loss (NIHL) is a complex disease induced by a combination of genetic and environmental factors. Paraoxonase2 (PON2) gene involved in the regulation of reactive oxygen species, and affecting the vulnerability of cochlea to NIHL, and ATPase, calcium-transporting, plasma membrane 2 (ATP2B2) gene which encodes plasma membrane calcium-transporting ATPase isoform 2 (PMCA2) are the candidate genes relating to the attack of NIHL. In this study, we investigated whether ATP2B2 and PON2 polymorphisms were associated with NIHL in Chinese of Han nationality population.

Methods

We performed a case-control study between six single nucleotide polymorphisms (SNPs) (rs1719571, rs3209637 and rs4327369 within ATP2B2, rs12026, rs7785846 and rs12704796 within PON2) and NIHL in 454 subjects. All the SNPs were genotypes, using the TaqMan MGB probe assay. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs) with logistic regression analysis to test the level of association for SNPs.

Results

In our study, 221 subjects with hearing loss and 233 subjects without hearing loss were recruited. The frequencies of the CG and CG + GG genotype of rs12026 (PON2) conferred risk factors for NIHL with adjusted OR values of 2.62 (95% CI, 1.69–4.06) and 2.48 (95% CI, 1.63–3.78), respectively. This kind of significance was also found at locus rs7785846, where genotypes CT and CT + TT were the risk types, with adjusted ORs of 2.52 (95% CI, 1.62–3.93) and 2.35 (95% CI, 1.54–3.58), respectively. We performed stratified analysis per noise exposure level, when it came to rs7785846 and rs12026 in the >92 dB(A) noise exposure group, the subjects who carried heterozygote were of significantly (P<0.01) higher susceptibility to NIHL than homozygote carriers. By contrast, no significantly higher risk was found for any rs12704796 genotypes or any genotypes in ATP2B2 (P>0.05), which may suggest that these SNPs did not have significant effects on noise susceptibility across noise exposure.

Conclusions

Our research suggested that PON2 might play a role in the etiology of NIHL in Chinese of Han nationality population.     

A modified nebulization modality versus classical ultrasonic nebulization and oxygen-driven nebulization in facilitating airway clearance in patients with acute exacerbation of chronic obstructive pulmonary disease: a randomized controlled trial

Background

Ultrasonic nebulization (UN) and oxygen-driven nebulization (ON), two commonly used modalities for nebulization inhalation, are not ideally suitable for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods

A total of 91 patients with AECOPD were randomized to three groups given different nebulization modalities: ON, UN, and ultrasonic nebulization with warming and oxygen (UNWO). The sputum clearance, lung function, changes in physiological measures such as peripheral oxygen saturation (SpO₂) and tolerance to these nebulization modalities were recorded and compared among the three groups.

Results

The time to the first expectoration was shorter and the sputum volume was larger after UN and UNWO than after ON (both P<0.01). Compared with pre-nebulization, SpO₂ significantly increased (P<0.01) and the dyspnea decreased significantly (P<0.05) after UNWO. The SpO₂ and dyspnea post-UNWO were significantly better than those post-UN (P<0.01, P<0.05), but not statistically different from those post-ON (both P>0.05). UNWO demonstrated significantly greater comfort and longer duration of nebulization than UN (P<0.01, P<0.05), but no significant differences in these respects from ON (both P>0.05). Forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) decreased significantly after UNWO (P<0.05, P<0.01, and P<0.01, respectively).

Conclusions

UNWO may promote expectoration of sputum with fewer adverse reactions and a higher level of comfort than simple UN and ON. Therefore, it can be used as an adjuvant therapy for AECOPD patients.     

In-vivo anti-inflammatory and anti-pyretic activities of Manilkara zapota leaves in albino Wistar rats

Objective

To screen ethanolic extracts of Manilkara zapota leaves (Family: Sapotaceae) and its different solvent soluble fractions for possible anti-inflammatory, anti-pyretic activities in experimental albino Wistar rats.

Methods

Anti-inflammatory activity was evaluated by carrageenan induced paw edema method; anti-pyretic potential was determined by yeast-induced pyrexia method in albino Wistar rats.

Results

In evaluation of anti-inflammatory activity the crude ethanolic (300 mg/kg) and ethyl acetate extract (300 mg/kg) showed significant inhibition of paw edema by 91.98% and 92.41% (P<0.001) respectively at 4th h compared to standard diclofenac (86.08% inhibition). In anti-pyretic study by yeast-induced pyrexia in albino Wistar rats, the ethanol extract (300 mg/kg) reduced temperature from 37.90 °C to 37.41 °C (P<0.01) and 37.07 °C (P<0.001) in 3rd and 4th h respectively. Similarly, both petroleum ether and ethyl acetate fractions exhibited significant anti-pyretic property (P<0.001). The maximum body temperature lowering effect (36.86 °C) was noticed by petroleum ether fraction.

Conclusions

The findings of the studies demonstrated both anti-inflammatory and anti-pyretic activities of the leaves of Manilkara zapota which could be the therapeutic option against inflammatory disease and pyrexia.     

Evaluation of hepatoprotective effect of methanolic extract of Clitoria ternatea (Linn.) flower against acetaminophen-induced liver damage

Objective

To evaluate the hepatoprotective and antioxidant activity of Clitoria ternatea (C. ternatea) flower extract against acetaminophen-induced liver toxicity.

Methods

The antioxidant property of C. ternatea flower extract was investigated by employing established in vitro antioxidant assay. The C. ternatea flower extract was studied in this work for its hepatoprotective effect against acetaminophen-induced liver toxicity in mice. Activity was measured by monitoring the levels of aspartate aminotransferase, alanine aminotransferase, billirubin and glutathione with histopathological analysis.

Results

The amount of total phenolics and flavonoids were estimated to be 105.40±2.47 mg/g gallic acid equivalent and 72.21±0.05 mg/g catechin equivalent respectively. The antioxidant activity of C. ternatea flower extract was 68.9% at a concentration of 1 mg/mL and was also concentration dependant, with an IC₅₀ value of 327.00 µg/mL. The results of acetaminophen-induced liver toxicity experiment showed that mice treated with the extract (200 mg/kg) showed a significant decrease in alanine aminotransferase, aspartate aminotransferase, and bilirubin levels, which were all elevated in the paracetamol group (P<0.05). Meanwhile, the level of glutathione was found to be restored in extract treated animals compared to the groups treated with acetaminophen alone (P<0.05). Therapy of extract also showed its protective effect on histopathological alterations and supported the biochemical finding.

Conclusion

The present work confirmed the hepatoprotective effect of C. ternatea flower against model hepatotoxicant acetaminophen.     

Study of Biofilm Formation in C57Bl/6J Mice by Clinical Isolates of Helicobacter pylori

Background/Aim:

Despite the significant number of studies on H. pylori pathogenesis, not much data has been published concerning its ability to form biofilm in the host stomach. This study aims to evaluate the potential of clinical isolates of H. pylori to form biofilm in C57BL/6J mice model.

Materials and Methods:

Two strains of H. pylori were selected from a collection of clinical isolates; one (19B), an efficient biofilm producer and the other (4B), with weak biofilm-forming ability. Mice infected through gastric avages were examined after one and two weeks. Colonization was determined by CFU and urease activity; the anti-H. pylori IgA was measured by ELISA, and chronic infections were evaluated by histopathology. Bacterial communities within mucosal sections were studied by immunofluorescence and scanning electron microscopy (SEM).

Results:

Successful infection was obtained by both test strains. Strain 19B with higher ability to form biofilm in vitro also showed a higher colonization rate in the mice stomach one week after infection. Difference (P < 0.05) in IgA titers was observed between the infected mice and the controls as well as between 19B and 4B infected mice, two weeks after the last challenge. Immunofluorescence and SEM results showed tightly colonizing H. pylori in stomach mucosal sections and in squamous and glandular epithelium.

Conclusion:

H. pylori is able to form biofilm in the mouse stomach and induce IgA production, reflecting the same potential as in humans. Firm attachment of coccoid form bacteria to host cells suggests the importance of this state in biofilm formation by H. pylori. Occurrence of biofilm in squamous and glandular epithelium of the mouse stomach proposes that H. pylori can all parts of the upper gastrointestinal tract.     

Mutagenic potency of Helicobacter pylori in the gastric mucosa of mice is determined by sex and duration of infection

Helicobacter pylori is a human carcinogen, but the mechanisms evoked in carcinogenesis during this chronic inflammatory disease remain incompletely characterized. We determined whether chronic H. pylori infection induced mutations in the gastric mucosa of male and female gpt delta C57BL/6 mice infected for 6 or 12 mo. Point mutations were increased in females infected for 12 mo. The mutation frequency in this group was 1.6-fold higher than in uninfected mice of both sexes (P < 0.05). A:T-to-G:C transitions and G:C-to-T:A transversions were 3.8 and 2.0 times, respectively, more frequent in this group than in controls. Both mutations are consistent with DNA damage induced by oxidative stress. No increase in the frequency of deletions was observed. Females had more severe gastric lesions than males at 6 mo postinfection (MPI; P < 0.05), but this difference was absent at 12 MPI. In all mice, infection significantly increased expression of IFNγ, IL-17, TNFα, and iNOS at 6 and 12 mo, as well as H. pylori–specific IgG1 levels at 12 MPI (P < 0.05) and IgG2c levels at 6 and 12 MPI (P < 0.01 and P < 0.001). At 12 MPI, IgG2c levels in infected females were higher than at 6 MPI (P < 0.05) and also than those in infected males at 12 MPI (P < 0.05). Intensity of responses was mediated by sex and duration of infection. Lower H. pylori colonization indicated a more robust host response in females than in males. Earlier onset of severe gastric lesions and proinflammatory, Th1-biased responses in female C57BL/6 mice may have promoted mutagenesis by exposing the stomach to prolonged oxidative stress.     

Development of an ELISA for Quantitative Detection of Immunoglobulin G (IgG) and IgA Antibodies to Helicobacter pylori for Use in Korean Patients with H. pylori-Associated Diseases

Background/Aims

We aimed to develop a quantitative enzyme-linked immunosorbent assay (ELISA) using whole-cell lysates of Helicobacter pylori 51 and to investigate its validity.

Methods

Data from 300 plates were obtained by two different operators. Standard sera were used to make a standard curve to analyze the quantity of anti-H. pylori immunoglobulin G (IgG) and IgA antibody. We obtained reproducible data with fewer dilutions of samples by the addition of serially diluted standard serum to each ELISA plate. To evaluate the validity of this ELISA, the 114 H. pylori-positive and -negative subjects were stratified into four age groups, i.e., 0 to 4, 5 to 9, 10 to 15, and 20 to 29 years, before testing.

Results

The mean IgG-antibody titers in H. pylori-positive and -negative subjects were 1,766.4 IU/mL and 654.3 IU/mL (p<0.001). The mean IgA-antibody titers in H. pylori-positive and -negative subjects were 350.1 IU/mL and 193.5 IU/mL (p<0.001). Anti-H. pylori IgG and IgA titers in the four age groups were higher in H. pylori-positive subjects than in H. pylori-negative subjects (p<0.05).

Conclusions

Using the current ELISA based on whole-cell lysates of H. pylori 51, reliable anti-H. pylori antibody titers were obtained regardless of the subject''s age.     

Mechanical ventilation modulates Toll-like receptors 2, 4, and 9 on alveolar macrophages in a ventilator-induced lung injury model

Objective

To investigate the role of Toll-like receptor 2 (TLR2), TLR4, TLR9 and myeloid differentiation factor 88 (MyD88) on alveolar macrophages in ventilator-induced lung injury (VILI).

Methods

Male, adult pathogen-free Sprague-Dawley rats weighing 300-350 g were used in this study. Animals were tracheotomized and allowed to breathe spontaneously for 4 h or mechanically ventilated for 4 h with low or high tidal volume (7 or 40 mL/kg). TLR2, TLR4, and TLR9, MyD-88 and NF-κΒ of alveolar macrophages’ expression under the different ventilation conditions were detected. Pulmonary permeability, lung inflammatory, IL-6 and IL-1β were assessed as well.

Results

Rats subjected to high tidal volume showed significantly greater pulmonary permeability and lung inflammatory than the control rats. Alveolar macrophages from rats subjected to high tidal volume also showed significantly higher protein expression of TLR2 (0.59±0.049 vs. 0.35±0.036 and 0.36±0.031, both P<0.001), TLR4 (0.845±0.0395 vs. 0.401±0.026 and 0.403±0.020, both P<0.001), TLR9 (0.727±0.074 vs. 0.383±0.039 and 0.367±0.043, both P<0.001), MyD-88 (1.01±0.060 vs. 0.485±0.045 and 0.507±0.046, both P<0.001) and NF-κΒ (0.776±0.067 vs. 0.448±0.043 and 0.481±0.047, both P<0.001), as well as significantly higher concentrations of IL-6 (7.32±0.24 vs. 2.42±0.13 and 2.44±0.32, both P<0.001) and IL-1β (139.95±9.37 vs. 53.63±5.26 and 53.55±6.63, both P<0.001) than the control and low tidal volume group.

Conclusions

The overexpression of TLR2, TLR4, and TLR9 on alveolar macrophages and release of pro-inflammatory cytokines play a role in VILI.     

The Effects of Broccoli Sprout Extract Containing Sulforaphane on Lipid Peroxidation and Helicobacter pylori Infection in the Gastric Mucosa

Background/Aims

The aims of this study were to investigate whether a broccoli sprout extract containing sulforaphane (BSES) inhibited the Helicobacter pylori infection density and exerted an antioxidative effect on gastric mucosal damage.

Methods

The enrolled subjects were randomized in a double-blinded manner into three groups. Finally, 33 H. pylori (+) BSES treatment subjects (group A), 28 H. pylori (+) placebo subjects (group B), and 28 H. pylori (−) BSES treatment subjects (group C) were studied. H. pylori infection density was indirectly quantified by a ¹³C-urea breath test (UBT), and the ammonia concentration in gastric juice aspirates was measured through gastroscopic examination. Malondialdehyde (MDA), an oxidative damage biomarker, and reduced glutathione (GSH), an antioxidant biomarker, were measured in the gastric mucosa by an enzyme-linked immunosorbent assay.

Results

BSES treatment did not significantly affect the UBT values or ammonia concentration in group A (p=0.634 and p=0.505, respectively). BSES treatment did significantly reduce mucosal MDA concentrations in group A (p<0.05) and group C (p<0.001), whereas the gastric mucosal GSH concentrations did not differ before and after treatment in any of the groups.

Conclusions

BSES did not inhibit the H. pylori infection density. However, BSES prevented lipid peroxidation in the gastric mucosa and may play a cytoprotective role in H. pylori-induced gastritis.     

Homocysteine and markers of inflammation in acute coronary syndrome

BACKGROUND:

An elevated level of homocysteine (Hcy) has been shown to be a cardiovascular risk factor in the majority of research studies. Recently, it was found to be associated with new risk factors such as inflammatory markers.

OBJECTIVES:

To investigate the distribution of plasma total Hcy (tHcy) and the levels of inflammatory markers in patients with acute coronary syndrome (ACS), and to evaluate the association between these parameters and the severity of the disease.

METHODS:

A total of 122 patients with ACS and 80 control subjects were recruited from the cardiac intensive care unit of the Military Hospital of Tunis, Tunisia. Lipid profile and the levels of tHcy, high-sensitivity C-reactive protein (HsCRP), interleukin (IL)-6, IL-8, IL-1β and tumour necrosis factor-alpha (TNFα) were determined for all participants. The distribution of these parameters were compared between groups and according to the number of diseased vessels in patients with ACS.

RESULTS:

ACS patients had significantly elevated levels of tHcy (P<0.01), HsCRP (P<0.001), IL-6 (P<0.001), TNFα (P<0.001), folates (P<0.05) and vitamin B₁₂ (P<0.001), but lower high-density lipoprotein cholesterol (P<0.05) levels. The analysis of the association between these parameters and the number of diseased vessels showed significant differences in tHcy, HsCRP, IL-6 and TNFα, with positive correlations. Significantly negative correlations were found between the number of diseased vessels and folate (r=−0.34; P<0.01), and vitamin B₁₂ (r=−0.22; P<0.01).

CONCLUSION:

Elevated levels of tHcy, IL-6, TNFα and HsCRP appear to be associated with a greater number of diseased arteries and, consequently, the severity of coronary artery disease.     

Lentivirus vector-mediated Rho guanine nucleotide dissociation inhibitor 2 induces beta-2 adrenergic receptor desensitization in β2AR desensitization mice model

Background

It is well-known that chronic administration of β₂AR agonists can induce β₂AR desensitization. Our previous study showed that Rho guanine nucleotide dissociation inhibitor 2 (RhoGDI2) overexpression induced beta-2 adrenergic receptor (β₂AR) desensitization in airway smooth muscle cells. The purpose of this study was to further study the function of RhoGDI2 in β₂AR desensitization by β₂AR desensitization mouse model.

Methods

Studies were performed using a β₂AR desensitization mice model induced by salbutamol. The mice were randomly divided into five groups (n=45): RhoGDI2 overexpression group (n=10); RhoGDI2 siRNA group (n=10); empty viral vector group (n=10); experimental control group (n=10); blank control group—without any drug treatment (n=5). The first four groups were used the same methods and the same dose to establish β₂AR desensitization mice model by salbutamol. The first three groups that salbutamol-treated were used for intratracheal delivery of lentiviral vectors. Airway hyperreactivity was measured through a whole-body plethysmograph system. RhoGDI2, β₂AR, GRK2 mRNA and protein expression levels were then detected by RT-PCR and western blot analyses in fresh lung tissues. As well as the activity of GRK was assessed by light-dependent phosphorylation of rhodopsin.

Results

We successfully constructed β₂AR desensitization mouse model. As expected, airway responsiveness after inhaling acetylcholine chloride (Ach) was markedly increased in the RhoGDI2 overexpression group compared to experimental control group and blank control group when concentrations of Ach was 45 mg/mL (all P<0.05), while, it was markedly decreased in the RhoGDI2 siRNA group compared to experimental control group (P<0.05). RhoGDI2, GRK2 expressions and GRK enzymatic activity were significantly increased in RhoGDI2 overexpression group compared to experimental control group and blank control group (all P<0.05). RhoGDI2, GRK2 expressions and GRK enzymatic activity were significantly decreased in RhoGDI2 siRNA group compared to experimental control group and blank control group (all P<0.05). Conversely, β₂AR expression were significantly lower in RhoGDI2 overexpression group compared to experimental control group and blank control group (all P<0.05), exhibiting an inverse correlation with RhoGDI2 expression.

Conclusions

To sum up, our present studies found that RhoGDI2 might induce β₂AR desensitization and GRK2 might take part in RhoGDI2-mediated β₂AR desensitization.