N-acylhomoserine lactone (AHL)-based quorum sensing (QS) is important for the regulation of proteobacterial virulence determinants. Thus, the inhibition of AHL synthases offers non-antibiotics-based therapeutic potentials against QS-mediated bacterial infections. In this work, functional AHL synthases of Pseudomonas aeruginosa LasI and RhlI were heterologously expressed in an AHL-negative Escherichia coli followed by assessments on their AHLs production using AHL biosensors and high resolution liquid chromatography–mass spectrometry (LCMS). These AHL-producing E. coli served as tools for screening AHL synthase inhibitors. Based on a campaign of screening synthetic molecules and natural products using our approach, three strongest inhibitors namely are salicylic acid, tannic acid and trans-cinnamaldehyde have been identified. LCMS analysis further confirmed tannic acid and trans-cinnemaldehyde efficiently inhibited AHL production by RhlI. We further demonstrated the application of trans-cinnemaldehyde inhibiting Rhl QS system regulated pyocyanin production in P. aeruginosa up to 42.06%. Molecular docking analysis suggested that trans-cinnemaldehyde binds to the LasI and EsaI with known structures mainly interacting with their substrate binding sites. Our data suggested a new class of QS-inhibiting agents from natural products targeting AHL synthase and provided a potential approach for facilitating the discovery of anti-QS signal synthesis as basis of novel anti-infective approach.
The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed.
In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18–21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA.
Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study.
PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in Singapore was shown to be immunogenic with a clinically acceptable-safety profile.
This study has been registered at http://www.clinicaltrials.govNCT00808444 and NCT01119625.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2334-14-530) contains supplementary material, which is available to authorized users.
Pneumococcal conjugate vaccine; Immunogenicity; Safety; Non-typeable Haemophilus influenzae; Infant; Toddler; Singapore; Malaysia
Proliferation of vascular smooth muscle cells (VSMCs) triggered by inflammatory stimuli and oxidative stress contributes importantly to atherogenesis. The association of green tea consumption with cardiovascular protection has been well documented in epidemiological observations, however, the underlying mechanisms remain unclear. This study aimed to elucidate the effects of the most active green tea catechin derivative, (−)-epigallocatechin-3-gallate (EGCG), in human aortic smooth muscle cells (HASMCs), focusing particularly on the role of a potent anti-inflammatory and antioxidative enzyme heme oxygenase-1 (HO-1). We found that pretreatment of EGCG dose- and time-dependently induced HO-1 protein levels in HASMCs. EGCG inhibited interleukin- (IL-)1β-induced HASMC proliferation and oxidative stress in a dose-dependent manner. The HO-1 inducer CoPPIX decreased IL-1β-induced cell proliferation, whereas the HO-1 enzyme inhibitor ZnPPIX significantly reversed EGCG-caused growth inhibition in IL-1β-treated HASMCs. At the molecular level, EGCG treatment significantly activated nuclear factor erythroid-2-related factor (Nrf2) transcription activities. These results suggest that EGCG might serve as a complementary and alternative medicine in the treatment of these pathologies by inducing HO-1 expression and subsequently decreasing VSMC proliferation.
The LRRK2 gene has been associated with both familial and sporadic forms of Parkinson's disease (PD). The G2019S variant is commonly found in North African Arab and Caucasian PD patients, but this locus is monomorphic in Asians. The G2385R and R1628P variants are associated with a higher risk of developing PD in certain Asian populations but have not been studied in the Malaysian population. Therefore, we screened the G2385R and R1628P variants in 1,202 Malaysian subjects consisting of 695 cases and 507 controls. The G2385R and R1628P variants were associated with a 2.2-fold (P = 0.019) and 1.2-fold (P = 0.054) increased risk of PD, respectively. Our data concur with other reported findings in Chinese, Taiwanese, Singaporean, and Korean studies.
Data analysis based on breast cancer risk factors such as age, race,
breastfeeding, hormone replacement therapy, family history, and obesity was
conducted on breast cancer patients using a new enhanced computerized database
management system. My Structural Query Language (MySQL) is selected as the
application for database management system to store the patient data collected
from hospitals in Malaysia. An automatic calculation tool is embedded in this
system to assist the data analysis. The results are plotted automatically and a
user-friendly graphical user interface is developed that can control the MySQL
database. Case studies show breast cancer incidence rate is highest among Malay
women, followed by Chinese and Indian. The peak age for breast cancer incidence
is from 50 to 59 years old. Results suggest that the chance of
developing breast cancer is increased in older women, and reduced with
breastfeeding practice. The weight status might affect the breast cancer risk
differently. Additional studies are needed to confirm these findings.
Breast cancer patients; Computerized database; Hospital management system
This study aims to evaluate the learning characteristics of students using a matrix framework of learning approaches (MFLA) in a Malaysian public university. A survey form based on Biggs’s study process questionnaire (SPQ) was distributed to a total of 350 students. This study employed a descriptive correlation research design to address the research objectives. The findings revealed that Malaysian students are prone to applying the achieving approach in their studies. The achieving approach is the most preferable learning characteristic. The results also indicated that four of the nine hypothetical learning approaches exist, two of which are positive in nature. As a result, a proposed teaching method based on the MFLA was introduced to suit the needs of these major learning characteristics among students.
Student approaches to learning; Matrix framework of learning approaches; Malaysian universities
Our study aimed to investigate the association of CYP2E1 C-1019T RsaI and T7678A DraI polymorphisms and factors such as age, gender and ethnicity to the risk of gastrointestinal cancer (GIC) in Malaysians.
520 consented healthy blood donors with no previous GIC record and 175 patients with GIC.
C-1019T RsaI and T7678A DraI genotyping of CYP2E1 gene; direct sequencing.
This study reveals that the variant c2 allele and carrier with at least one c2 allele of C-1019T single nucleotide polymorphism (SNP) significantly increased the risk of GIC but no significant association was found between T7678A SNP and combined analysis of C-1019T and T7678A SNPs to risk of GIC. The Malaysian Chinese had greater risk of GIC compared with the Malays, Indians and KadazanDusun. An increased risk of GIC was observed in individuals aged >40 years and women had a 2.22-fold and 1.58-fold increased risk of stomach and colorectal cancers, respectively, when compared with men.
The future research should be conducted with a larger sample population and including the gene–gene and gene–environmental interactions.
Our study suggests that the rare c2 allele and carrier with at least one c2 allele of CYP2E1 RsaI polymorphism significantly elevated the risk of GIC and may be used as a genetic biomarker for early screening of GIC in Malaysians. The risk age-group has been shifted to a younger age at 40s and women showed a significant greater risk of stomach and colorectal cancers than men.
Gastroenterology; Molecular Biology
Proteobacteria produce N-acylhomoserine lactones as signaling molecules, which will bind to their cognate receptor and activate quorum sensing-mediated phenotypes in a population-dependent manner. Although quorum sensing signaling molecules can be degraded by bacteria or fungi, there is no reported work on the degradation of such molecules by basidiomycetous yeast. By using a minimal growth medium containing N-3-oxohexanoylhomoserine lactone as the sole source of carbon, a wetland water sample from Malaysia was enriched for microbial strains that can degrade N-acylhomoserine lactones, and consequently, a basidiomycetous yeast strain WW1C was isolated. Morphological phenotype and molecular analyses confirmed that WW1C was a strain of Trichosporon loubieri. We showed that WW1C degraded AHLs with N-acyl side chains ranging from 4 to 10 carbons in length, with or without oxo group substitutions at the C3 position. Re-lactonisation bioassays revealed that WW1C degraded AHLs via a lactonase activity. To the best of our knowledge, this is the first report of degradation of N-acyl-homoserine lactones and utilization of N-3-oxohexanoylhomoserine as carbon and nitrogen source for growth by basidiomycetous yeast from tropical wetland water; and the degradation of bacterial quorum sensing molecules by an eukaryotic yeast.
basidiomycetous; biosensor; lactonase; N-acylhomoserine lactone; quorum sensing; quorum quenching; Rapid Resolution Liquid Chromatography; Trichosporon loubieri; yeast
AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology.
METHODS: Patients with psoriasis treated with MTX referred to the Department of Gastroenterology, Tan Tock Seng Hospital for liver biopsy were identified and retrospectively studied. Patient case notes and electronic records were retrieved from the hospital database and relevant data collated. Histological changes of liver biopsies were staged according to Roengik score. The factors assessed were age, gender, ethnicity, cumulative dose of MTX, presence of comorbid conditions such as diabetes, hypertension, hyperlipidemia, and ethanol use. We also assessed the histological change in those with multiple liver biopsies. Statistical analysis was performed using Stata V.9.2.
RESULTS: There were altogether 59 patients (median age 50 years old, range 22-81 years old, male, 88%) with 98 biopsies liver biopsies; 6 normal [median cumulative dose (MCD), 2285 mg]; 62 grade I (MCD 2885 mg), 23 grade II (MCD 1800 mg) and 7 grade III (MCD 1500 mg). There was no grade IV or cirrhosis. The prevalence of liver fibrosis (grade III) was 12%. Of the factors assessed, diabetes (P = 0.001) and hypertension (P = 0.003) were significant for fibrosis on univariate analysis but not on multivariate analysis. Of the 26 patients who had more than one biopsy (median 2, range 2-6), 57.7% (n = 15) were stable, 34.6% (n = 9) had progression and 7.7% (n = 2) had regression of histological grades. On univariate analysis, non-Chinese ethnicity (P = 0.031), diabetes (P = 0.018), and hyperlipidemia (P = 0.011) were predictive of progression of grades, but these were not significant on multivariate analysis.
CONCLUSION: Liver fibrosis in Asian psoriatic population on MTX is comparable to the West. Cumulative dose was not associated with liver fibrosis. Metabolic syndrome is important factors.
Hepatotoxicity; Liver fibrosis; Methotrexate; Risk factors; Cirrhosis
Quorum sensing is a system of stimuli and responses in relation to bacterial cell population density that regulates gene expression, including virulence determinants. Consequently, quorum sensing has been an attractive target for the development of novel anti-infective measures that do not rely on the use of antibiotics. Anti-quorum sensing has been a promising strategy to combat bacterial infections as it is unlikely to develop multidrug resistant pathogens since it does not impose any selection pressure. A number of anti-quorum sensing approaches have been documented and plant-based natural products have been extensively studied in this context. Plant matter is one of the major sources of chemicals in use today in various industries, ranging from the pharmaceutical, cosmetic, and food biotechnology to the textile industries. Just like animals and humans, plants are constantly exposed to bacterial infections, it is therefore logical to expect that plants have developed sophisticated of chemical mechanisms to combat pathogens. In this review, we have surveyed the various types of plant-based natural products that exhibit anti-quorum sensing properties and their anti-quorum sensing mechanisms.
anti-infective; autoinducer; bacterial cell-to-cell communication; biofilm; infectious diseases; N-acylhomoserine lactones; pathogen; quorum quenching; quorum sensing; virulence factors
Demyelination contributes to the functional impairment of irradiation injured spinal cord. One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2+-GFP+-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs), could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2+-GFP+-OPCs and transplanted them into the rats’ cervical 4–5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2+-GFP+-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2+-GFP+-OPCs primarily differentiated into adenomatous polyposis coli (APC+) oligodendrocytes (54.6±10.5%). The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E) and electron microscopy demonstrated that the engrafted Olig2+-GFP+-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2+-GFP+-OPCs. We concluded that OPC transplantation is a feasible therapy to repair the irradiated lesions in the central nervous system (CNS).
Maternal nutrition has critical effects on the developing structures and functions of the fetus. Malnutrition during pregnancy can result in low birth weight and small for gestational age babies, increase risk for infection, and impact the immune system. Long-chain polyunsaturated fatty acids (PUFAs) have been reported to have immunomodulatory effects. Decreased consumption of omega-6 PUFAs, in favor of more anti-inflammatory omega-3 PUFAs in modern diets, has demonstrated the potential protective role of omega-3 PUFAs in allergic and respiratory diseases. In this paper, we examine the role of PUFAs consumption during pregnancy and early childhood and its influence on allergy and respiratory diseases. PUFAs act via several mechanisms to modulate immune function. Omega-3 PUFAs may alter the T helper (Th) cell balance by inhibiting cytokine production which in turn inhibits immunoglobulin E synthesis and Th type 2 cell differentiation. PUFAs may further modify cellular membrane, induce eicosanoid metabolism, and alter gene expression. These studies indicate the benefits of omega-3 PUFAs supplementation. Nevertheless, further investigations are warranted to assess the long-term effects of omega-3 PUFAs in preventing other immune-mediated diseases, as well as its effects on the later immunodefense and health status during early growth and development.
Clinical information about genotypically different clones of biofilm-producing Staphylococcus aureus is largely unknown. We examined whether different clones of methicillin-sensitive and methicillin-resistant S. aureus (MSSA and MRSA) differ with respect to staphylococcal microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) in biofilm formation. The study used 60 different types of spa and determined the phenotypes, the prevalence of the 13 MSCRAMM, and biofilm genes for each clone. The current investigation was carried out using a modified Congo red agar (MCRA), a microtiter plate assay (MPA), polymerase chain reaction (PCR), and reverse transcriptase polymerase chain reaction (RT-PCR). Clones belonging to the same spa type were found to have similar properties in adheringto the polystyrene microtiter plate surface. However, their ability to produce slime on MCRA medium was different. PCR experiments showed that 60 clones of MSSA and MRSA were positive for 5 genes (out of 9 MSCRAMM genes). icaADBC genes were found to be present in all the 60 clones tested indicating a high prevalence, and these genes were equally distributed among the clones associated with MSSA and those with MRSA. The prevalence of other MSCRAMM genes among MSSA and MRSA clones was found to be variable. MRSA and MSSA gene expression (MSCRAMM and icaADBC) was confirmed by RT-PCR.
The quest for universal memory is driving the rapid development of memories with superior all-round capabilities in non-volatility, high speed, high endurance and low power. Phase-change materials are highly promising in this respect. However, their contradictory speed and stability properties present a key challenge towards this ambition. We reveal that as the device size decreases, the phase-change mechanism changes from the material inherent crystallization mechanism (either nucleation- or growth-dominated), to the hetero-crystallization mechanism, which resulted in a significant increase in PCRAM speeds. Reducing the grain size can further increase the speed of phase-change. Such grain size effect on speed becomes increasingly significant at smaller device sizes. Together with the nano-thermal and electrical effects, fast phase-change, good stability and high endurance can be achieved. These findings lead to a feasible solution to achieve a universal memory.
The genus Rhodococcus has proved to be a promising option for the cleanup of polluted sites and application of a microbial biocatalyst. Rhodococcus sp. strain R04, isolated from oil-contaminated soil, can biodegrade polychlorinated biphenyls. Here we report the draft genome sequence of Rhodococcus sp. strain R04, which could be used to predict genes for xenobiotic biodegradation and provide important insights into the applications of this strain.
Prevalence of allergic diseases has increased in the last years. Data on recurrent wheezing (≥3 episodes) in infancy is scarce. The aim of this study was to verify changing in prevalence of recurrent wheezing infants in the south of Brazil.
Cross-sectional study using a standardized and validated questionnaire (EISL: Estudio Internacional sobre Sibilancias en Lactantes) with questions: Has your baby had wheezing or whistling in the chest area or bronchitis in the first 12 months of life? Has your baby had 3 or more wheezing episodes in the first year of life? Parents of infants, ages 12 to 15 months that attended to Health Centers for routine immunization were interviewed between August 2005 to December 2006 (EISL Phase I) and September 2009 to September 2010 (EISL Phase III). Categorical variables are shown as proportion and differences verified by chi-square test, and continuous variables were expressed as mean ± SD and analyzed by Student t test.
Three thousand three parents of infants answered questionnaire in the EISL Phase I, and 45.4% had had at least one wheezing episode; 50.7% were male, and 22.6% had recurrent wheezing episode starting at 5.5 ± 3.1 months. Five years later, in the EISL Phase III, 1003 parents participated in the survey: 40.6% had at least one wheezing episode (P = 0.46), 51.1% were male, and 19.8% had recurrent wheezing (P = 0.1) starting at 6.1 ± 3 months (P = 0.06).
Recurrent wheezing in infancy is highly prevalent and starts early in life. In our population, recurrent wheezing rates did not modify in the time period of study.
There are controversies in treating recurrent wheezing (≥3 episodes) in pre-school children. The aim of this study was to verify changes in treatment of recurrent wheezing infants.
Cross-sectional study using a standardized and validated questionnaire (EISL: Estudio Internacional sobre Sibilancias en Lactantes) that covers physician diagnosis of asthma, and frequency, severity, and treatment of wheezing episodes. Regarding treatment specific questions are: Has your baby been treated with inhaled short-acting β2-agonists by metered dose inhaler or nebulizer? Has your baby been treated with inhaled corticosteroids? Has your baby been treated with antileukotrienes? Has your baby been treated with oral corticosteroids? Parents of infants, ages 12 to 15 months that attended to Health Centers for routine immunization were interviewed between August/2005 to December/2006 (EISL Phase I) and September/2009 to September/2010 (EISL Phase III). Categorical variables are showed as proportion and differences verified by chi-square test.
Three thousand and 3 parents of infants answered questionnaire in the EISL Phase I and 22.6% had recurrent wheezing episodes. Five years later, in the EISL Phase III, 1003 parents participated in the survey and 19.8% had recurrent wheezing (P = 0.1). Inhaled short-acting β2-agonists continued to be prescribed in the same frequency (89.6% vs 86.5%, P = 0.21), however anti-asthmatic drugs were more used [antileukotrienes (6.9% vs 33%, P < 0.001), inhaled steroids (23.6% vs 37.5%, P = 0.001) and oral steroids (18.6% vs 26.5%, P = 0.01)] and doctor diagnosis of asthma has increased (16.2% vs 23%, P = 0.03). There were reductions on night-time symptoms (73% vs 61.5%, P = 0.001), severity (59.3% vs 42%, P = 0.001) and emergency room visits (69.3% vs 41.5%, P < 0.001) for recurrent wheezing infants, but no difference was seen in hospitalization (17.1% vs 12.5%, P = 0.12).
Recurrent wheezing treatment in infancy has increased in past years and may have contributed for reducing emergency room visits, night-time symptoms and severity for wheezing infants.
Paracetamol (PCM) and antibiotic (ATB) use have been associated with risk for wheezing and asthma in children. The aim of this study was to verify the association of recurrent wheezing (≥3 episodes) in infancy and use of ATB or PCM in the first year of life.
Cross-sectional study using a standardized and validated questionnaire (EISL: Estudio Internacional sobre Sibilancias en Lactantes) with questions: Has your baby had wheezing or whistling in the chest area or bronchitis in the first 12 months of life? Has your baby had 3 or more wheezing episodes in the first year of life? How often has your baby used antibiotics in the first year of life? How often has your baby used paracetamol in the first year of life? Parents of infants, ages 12 to 15 months that attended to Health Centers for routine immunization were interviewed between September 2009 to September 2010 (EISL Phase III). Risk was demonstrated using Odds ratio and 95% CI.
One thousand and 3 parents participated in the survey and 19.8% of infants had recurrent wheezing starting at 6.1 ± 3 months. The use of PCM was not related to the presence of recurrent wheezing [No PCM (OR = 0.91; 95% CI, 0.38-2.19; P = 0.83), PCM 1–3 times (OR = 1.21; 95% CI, 0.77-1.91; P = 0.4), PCM 4–6 times (OR = 1.21; 95% CI, 0.77-1.9; P = 0.41) and PCM ≥7 times (OR = 0.76; 95% CI, 0.51-1.13; P = 0.17)], while more frequent use of ATB reduced the risk of recurrent wheezing in the first year of life [No ATB (OR = 2.18; 95% CI, 1.35-3.51; P = 0.001), ATB 1–3 times (OR = 1.39; 95% CI, 0.93-2.07; P = 0.1), ATB 4–6 times (OR = 0.37; 95% CI, 0.22-0.62; P = 0.001) and PCM≥7 times (OR = 0.22; 95% CI, 0.07-0.66; P = 0.001)].
The frequent use of ATB reduced the risk of recurrent wheezing in the first year of life unlike PCM that was not associated with recurrent wheezing in this study population.
We report the production and degradation of quorum sensing N-acyl-homoserine lactones by bacteria isolated from Malaysian montane forest soil. Phylogenetic analysis indicated that these isolates clustered closely to the genera of Arthrobacter, Bacillus and Pseudomonas. Quorum quenching activity was detected in six isolates of these three genera by using a series of bioassays and rapid resolution liquid chromatography analysis. Biosensor screening and high resolution liquid chromatography-mass spectrometry analysis revealed the production of N-dodecanoyl-L-homoserine lactone (C12-HSL) by Pseudomonas frederiksbergensis (isolate BT9). In addition to degradation of a wide range of N-acyl-homoserine lactones, Arthrobacter and Pseudomonas spp. also degraded p-coumaroyl-homoserine lactone. To the best of our knowledge, this is the first documentation of Arthrobacter and Pseudomonas spp. capable of degrading p-coumaroyl-homoserine lactone and the production of C12-HSL by P. frederiksbergensis.
Arthrobacter; Bacillus; liquid chromatography mass spectrometry (LC-MS); N-acylhomoserine lactone; N-dodecanoyl-L-homoserine lactone; p-coumaroylhomoserine lactone; Pseudomonas frederiksbergensis; quorum quenching; quorum sensing; rapid resolution liquid chromatography (RRLC)
Diabetes is the sixth most common cause of death in the US and causes significant postoperative mortality and morbidity.
To characterize the impact of diabetes among patients undergoing surgery for colorectal cancer.
This is is a retrospective cohort study.
Patients in the Nationwide Inpatient Sample (NIS) who had undergone colorectal cancer surgery between 1998 and 2005.
Using multivariate regression, we determined the association of diabetes status with postoperative mortality, postoperative complications, and length of stay.
An estimated 218,534 patients had undergone surgery for colorectal cancer. We categorized subjects by the presence of diabetes, the prevalence of which was 15%. Crude postoperative in-hospital mortality was lower among diabetics compared to non-diabetics (2.5% vs. 3.2%, P < 0.0001). Adjusted mortality was 23% lower in those with diabetes compared to non-diabetics (aOR 0.77; 95% CI: 0.71–0.84). Diabetics also had lower adjusted post-operative complications compared to non-diabetics (aOR 0.82; 95% CI: 0.79–0.84). In uninsured individuals and patients <50 years of age, there was no protective association between diabetes and either in-hospital mortality or postoperative complications.
In patients undergoing colorectal cancer surgery, those with diabetes had a 23% lower mortality and fewer postoperative complications compared to non-diabetics. The mechanisms underlying this unexpected observation warrant further investigation.
diabetes; nationwide; colorectal cancer; hyperglycemia
Right-sided diaphragmatic rupture is less common and more difficult to diagnose than left-sided lesion. It is rarely combined with the herniation of the abdominal organs into the thorax. High level of suspicion is the key to early diagnosis, and a delay in diagnosis is implicated with a considerable risk of mortality and morbidity. We experienced a case of right-sided diaphragmatic rupture combined with complete avulsion of the right kidney and herniation of the liver into the thoracic cavity.
Diaphragm; Kidney; Liver; Trauma; Diaphragm, trauma
CTX-M-14-type extended-spectrum β-lactamase was first detected in Salmonella enterica serovar London strains which were isolated from three hospitalized pediatric patients with gastroenteritis. The isolates had pulsed-field gel electrophoresis patterns identical to those of the previously isolated antimicrobial-susceptible strains from community-acquired gastroenteritis, suggesting the susceptible clone acquired the resistance.
To determine overall detection rates of lung cancer by low-dose CT (LDCT) screening and to compare histopathologic and imaging differences of detected cancers between high- and low-risk groups, this study included 6,406 asymptomatic Korean adults with ≥45 yr of age who underwent LDCT for lung cancer screening. All were classified into high- (≥20 pack-year smoking; 3,353) and low-risk (3,053; <20 pack-yr smoking and non-smokers) groups. We compared CT findings of detected cancers and detection rates between high- and low-risk. At initial CT, 35% (2,255 of 6,406) had at least one or more non-calcified nodule. Lung cancer detection rates were 0.36% (23 of 6,406). Twenty-one non-small cell lung cancers appeared as solid (n=14) or ground-glass opacity (GGO) (n=7) nodules. Cancer likelihood was higher in GGO nodules than in solid nodules (p<0.01). Fifteen of 23 cancers occurred in high-risk group and 8 in low-risk group (p=0.215). Therefore, LDCT screening help detect early stage of lung cancer in asymptomatic Korean population with detection rate of 0.36% on a population basis and may be useful for discovering early lung cancer in low-risk group as well as in high-risk group.
Mass Screening; Lung Neoplasms; Tomography, Spiral Computed; Smoking
AIM: To determine the radiosensitizing potential of docetaxel in human hepatocellular carcinoma SMMC-7721 cells and its mechanisms.
METHODS: SMMC-7721 cells were incubated with docetaxel at 0.125, 0.25, and 0.5 nmoL/L for 24 h and at 0.125 and 0.25 nmol/L for 48 h before irradiation. Radiation doses were given from 0 to 10 Gy. Cell survival was measured by a standard clonogenic assay after a 9-d incubation. The reactive oxygen species (ROS) and glutathione (GSH) are detected after being given the same dose of docetaxel for the same time.
RESULTS: The sensitization enhancement ratios (SER) for SMMC-7721 cells determined at the 50% survival level were 1.15, 1.21 and 1.49 at 0.125, 0.25, and 0.5 nmol/L for pre-incubation of 24 h, respectively; the SER were 1.42, 1.67 at 0.125 and 0.25 nmol/L, for pre-incubation of 48 h, respectively. The ROS of SMMC-7721 cells increased and GSH decreased after pretreatment with the same doses of docetaxel for 24 or 48 h.
CONCLUSION: A radiosensitizing effect of docetaxel could be demonstrated unambiguously in this cell line used. In addition, our data showed that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in SMMC-7721 cells, and ROS generation and GSH deletion may play a key role in the radiosensitizing effect of docetaxel.
Docetaxel; Hepatocellular carcinoma; SMMC-7721cell line; Radiosensitization; Reactive oxygen species
Non-alcoholic steatohepatitis (NASH) is associated with hepatic fibrogenesis. Despite well-known cholesterol-lowering action of statins, their mechanisms against NASH-mediated fibrogenesis remain unclear. This study aimed at investigating the in vitro and in vivo anti-fibrotic properties of fluvastatin (Flu).
Palmitate (PA)-induced changes in intracellular hydrogen peroxide levels in primary rat hepatocytes (PRHs) and human hepatoma cell line (HepG2) were quantified by dichlorofluorescein diacetate (DCF-DA) dye assay, whereas changes in expressions of NADPH oxidase gp91phox subunit, α-smooth muscle actin (α-SMA), and NFκB p65 nuclear translocation were quantified with Western blotting. Quantitative real-time polymerase chain reaction (q-PCR) was used to investigate mRNA expressions of pro-inflammatory genes (ICAM-1, IL-6, TNF-α). Conditioned medium (CM) from PA-treated PRHs was applied to cultured rat hepatic stellate cell line, HSC-T6, with or without Flu-pretreatment for 2 h. Pro-fibrogenic gene expressions (COL1, TIMP-1, TGF-β1, α-SMA) and protein expression of α-SMA were analyzed. In vivo study using choline-deficient L-amino acid defined (CDAA) diet-induced rat NASH model was performed by randomly assigning Wistar rats (n = 28) to normal controls (n = 4), CDAA diet with vehicles, and CDAA diet with Flu (5 mg/kg or 10 mg/kg) (n = 8 each) through gavage for 4 or 8 weeks. Livers were harvested for histological, Western blot (α-SMA), and q-PCR analyses for expressions of pro-inflammatory (IL-6, iNOS, ICAM-1) and pro-fibrogenic (Col1, α-SMA, TIMP-1) genes.
In vitro, Flu (1–20 μM) inhibited PA-induced free-radical production, gp91phox expression, and NFκB p65 translocation in HepG2 and PRHs, while CM-induced α-SMA protein expression and pro-fibrogenic gene expressions in HSC-T6 were suppressed in Flu-pretreated cells compared to those without pretreatment. Moreover, α-SMA protein expression was significantly decreased in HSC-T6 cultured with CM from PA-Flu-treated PRHs compared to those cultured with CM from PA-treated PRHs. Flu also reduced steatosis and fibrosis scores, α-SMA protein expression, mRNA expression of pro-inflammatory and pro-fibrogenic genes in livers of CDAA rats.
We demonstrated PA-induced HSC activation through paracrine effect of hepatocyte in vitro that was significantly suppressed by pre-treating HSC with Flu. In vivo, Flu alleviated steatosis-induced HSC activation and hepatic fibrogenesis through mitigating inflammation and oxidative stress, suggesting possible therapeutic role of Flu against NASH.
Non-alcoholic fatty liver disease; Steatohepatitis; Statins; Fibrogenesis; Hepatocyte; Paracrine effect