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1.
Nicolas Degand Justine Dautremer Benoît Pilmis Agnès Ferroni Fanny Lanternier Julie Bruneau Olivier Hermine Stéphane Blanche Xavier Nassif Olivier Lortholary Marc Lecuit 《Journal of clinical immunology》2017,37(7):727-731
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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.2.
M. Yaqoob L. P. Wang J. Memon J. Kashif S. Umar Z. Naseer M. F. Iqbal M. Fiaz C. P. Lu 《Molecular Genetics, Microbiology and Virology》2017,32(1):49-54
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.3.
Ragheda Yaseen Stefanie Blodkamp Petra Lüthje Friederike Reuner Lena Völlger Hassan Y. Naim Maren von Köckritz-Blickwede 《Journal of negative results in biomedicine》2017,16(1):2
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.4.
Fabiane Sônego Fernanda V. S. Castanheira Catarina V. Horta Alexandre Kanashiro Paula G. Czaikoski Dario S. Zamboni José Carlos Alves-Filho Fernando Q. Cunha 《Inflammation research》2018,67(5):435-443
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 DZ605.5.
Mara A. Correa Tatiane Canhamero Andrea Borrego Iana S. S. Katz José R. Jensen José Luiz Guerra Wafa H. K. Cabrera Nancy Starobinas Jussara G. Fernandes Orlando G. Ribeiro Olga M. Ibañez Marcelo De Franco 《Inflammation research》2017,66(11):969-980
Objective and design
Pristane-induced arthritis (PIA) in AIRmax mice homozygous for Slc11a1 R and S alleles was used to characterize the influence of Slc11a1 gene polymorphism on immune responses during disease manifestation. Previous reports demonstrated that the presence of the Slc11a1 S allele increased the incidence and severity of PIA in AIRmax SS , suggesting that this gene could interact with inflammatory loci to modulate PIA. We investigated the effects of Slc11a1 alleles on the activation of phagocytes during PIA.Treatment
Mice were injected intraperitoneally with two doses of 0.5 mL of mineral oil pristane at 60-day intervals. Arthritis development was accompanied for 180 days.Results
AIRmax SS mice showed differential peritoneal macrophage gene expression profiles during PIA, with higher expression and production of H2O2, NO, IL-1β, IL-6, TNF-α, and several chemokines. The presence of the Slc11a1 R allele, on the other hand, diminished the intensity of macrophage activation, restricting arthritis development.Conclusion
Our data demonstrated the fine-tuning roles of Slc11a1 alleles modulating macrophage activation, and consequent PIA susceptibility, in those mouse lines.6.
Background
Postmenopausal women experience estrogen deficiency-related menopausal symptoms (e.g., hot flashes and mood swings) and a dramatic increase in the incidence of chronic diseases. Although estrogen-replacement therapy (ERT) can reduce mortality from cardiovascular disease and improve osteoporosis and menopausal symptoms, its side effects have limited recent use. This study investigated the estrogen-like activity of aqueous extract from Agrimonia pilosa Ledeb.Methods
The estrogenic activity of A. pilosa was investigated by using several in vitro assays. The binding activity of A. pilosa on estrogen receptors was examined using a fluorescence polarization-based competitive binding assay. The proliferative activity of A. pilosa was also examined using MCF-7 cells. Furthermore, the effect of A. pilosa on the expression of 3 estrogen-dependent genes was assessed.Results
Using liquid chromatography-mass spectrometry, the 3 major peaks of A. pilosa aqueous extract were identified as apigenin-hexose, luteolin-glucuronide, and apigenin-glucuronide. The aqueous extract induced the proliferation of estrogen receptor-positive MCF-7 cells (p?<?0.05). A. pilosa-stimulated proliferation was blocked on adding the estrogen antagonist ICI 182,780. Moreover, A. pilosa treatment increased the mRNA expression of the estrogen-responsive genes pS2 and PR (p?<?0.05).Conclusions
These results suggest A. pilosa can be used to improve estrogen deficiency-related menopausal symptoms or to treat diseases in postmenopausal women.7.
Alessio Cortelazzo Claudio de Felice Silvia Leoncini Cinzia Signorini Roberto Guerranti Roberto Leoncini Alessandro Armini Luca Bini Lucia Ciccoli Joussef Hayek 《Inflammation research》2017,66(3):269-280
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.8.
Liang Shen Jiang Xu Lu Luo Haoyu Hu Xiangxiao Meng Xiwen Li Shilin Chen 《Chinese medicine》2018,13(1):58
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.9.
Nadine Alvarez Oscar Otero Frank Camacho Reinier Borrero Yanely Tirado Alina Puig Alicia Aguilar Cesar Rivas Axel Cervantes Gustavo Falero-Díaz Armando Cádiz María E Sarmiento Mohd Nor Norazmi Rogelio Hernández-Pando Armando Acosta 《BMC immunology》2013,14(Z1):S3
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.10.
Jung Eun Hwang Na Jin Kim Meiying Song Yinji Cui Eun Ju Kim In Ae Park Hye In Lee Hye Jin Gong Su Young Kim 《BMC medical education》2017,17(1):252
Background
In an integrated curriculum, multiple instructors take part in a course in the form of team teaching. Accordingly, medical schools strive to manage each course run by numerous instructors. As part of the curriculum management, course evaluation is conducted, but a single, retrospective course evaluation does not comprehensively capture student perception of classes by different instructors. This study aimed to demonstrate the need for individual class evaluation, and further to identify teaching characteristics that instructors need to keep in mind when preparing classes.Methods
From 2014 to 2015, students at one medical school left comments on evaluation forms after each class. Courses were also assessed after each course. Their comments were categorized by connotation (positive or negative) and by subject. Within each subject category, test scores were compared between positively and negatively mentioned classes. The Mann-Whitney U test was performed to test group differences in scores. The same method was applied to the course evaluation data.Results
Test results for course evaluation showed group difference only in the practice/participation category. However, test results for individual class evaluation showed group differences in six categories: difficulty, main points, attitude, media/contents, interest, and materials. That is, the test scores of classes positively mentioned in six domains were significantly higher than those of negatively mentioned classes.Conclusions
It was proved that individual class evaluation is needed to manage multi-instructor courses in integrated curricula of medical schools. Based on the students’ extensive feedback, we identified teaching characteristics statistically related to academic achievement. School authorities can utilize these findings to encourage instructors to develop effective teaching characteristics in class preparation.11.
Background
Anatomy in medical curricula is typically taught via pedagogy consisting of didactic lectures combined with a practical component. The practical component often includes traditional cadaveric dissection classes and/or workshops utilizing anatomical models, carefully prosected cadaveric material and radiology. The primary aim of this study was to determine if there is an association between attendance at practical classes in anatomy and student assessment outcomes. A secondary aim was to determine if student assessment outcomes were better when students preferentially attended workshops or prosection style practical classes.Method
We retrospectively examined practical attendance records and assessment outcomes from a single large anatomy subject (approx. 450 students) to identify how attendance at anatomy practical classes correlates with assessment outcome.Results
Students who scored above the median mark for each assessment attended significantly more practical classes than students who scored below the median assessment mark (Mann Whitney; p?<?0.001), and students who attended more than half the practical classes had significantly higher scores on assessments than students that attended less than half the practical classes (Mann Whitney; P?<?0.01). There was a statistically significant positive correlation between attendance at practical classes and outcomes for each assessment (Spearman’s correlation; p?<?0.01). There was no difference in assessment outcomes for students who preferentially attended more dissection compared to prosection style classes and vice versa (Mann Whitney; p?>?0.05).Conclusions
Our findings show there is an association between student attendance at practical classes and performance on anatomy assessment.12.
Background
ACTA2 encodes smooth muscle specific α-actin, a critical component or the contractile complex of vascular smooth muscle. Mutations in ACTA2 are the most common genetic cause of thoracic aortic aneurysm, and are also the cause of other disorders, including Moyamoya disease, coronary artery disease and stroke as well as Multisystemic Smooth Muscle Dysfunction Syndrome. We note that ACTA2 is also expressed in uterine smooth muscle, and this raises the possibility that women harboring ACTA2 mutations might exhibit uterine smooth muscle dysfunction.Case presentation
We present a young woman whose ACTA2 mutation was ascertained during pregnancy because of her father’s history of dissecting aneurysms. She was delivered at full term by cesarean section and subsequently had severe uterine hemorrhage due to uterine atony. Although her atony was successfully treated with uterotonic medications, she required blood transfusion.Conclusions
This case raises the possibility that women with ACTA2 mutations may be at risk of uterine muscle dysfunction and hemorrhage. Obstetricians should be alerted to and prepared for this possibility.13.
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.14.
Chi Zhou Jin Huang Guanglin Cui Hesong Zeng Dao Wen Wang Qiang Zhou 《BMC medical genetics》2018,19(1):219
Background
Fabry disease is an X-linked recessive lysosomal disorder caused by deficient enzymatic activity of α-galactosidase A (α-Gal A). The insufficient enzymatic activity leads to excessive accumulation of glycosphingolipids, the substrates of the enzyme, in lysosomes in organs and tissues. Mutations in the α-Gal A gene (GLA, Xq22) have been proven to be responsible for Fabry disease.Methods
In this study, we report a four-generation pedigree with left ventricular hypertrophy and chronic renal failure that was diagnosed by sequencing the GLA gene. An over expression system was constructed to evaluate the function of the detected mutation.Results
We identified a novel mutation in exon 6 of the GLA gene, p.Asn278Lys, which completely co-segregated with the disease phenotype. The protein level of α-Gal A was significantly lower in the variant group than in the wild-type group; additionally, the pharmacological chaperone 1-deoxy-galactonojirimycin (DGJ) effectively normalized the enzyme activity of α-Gal A and its decline at the protein level.Conclusions
This study is the first to report a novel loss-of-function mutation, p.Asn278Lys, in exon 6 of the GLA gene as a genetic aetiology for Fabry disease. In addition, we analysed the feasibility of DGJ as a therapeutic approach for this particular GLA mutation.15.
Juliane Friemel Markus Rechsteiner Marion Bawohl Lukas Frick Beat Müllhaupt Mickaël Lesurtel Achim Weber 《BMC clinical pathology》2016,16(1):7
Background
In the spectrum of molecular alterations found in hepatocellular carcinoma (HCC), somatic mutations in the WNT/β-catenin pathway and the p53/cell cycle control pathway are among the most frequent ones. It has been suggested that both mutations occur in a mutually exclusive manner and they are used as molecular classifiers in HCC classification proposals.Case presentation
Here, we report the case of a treatment-naïve mixed hepatocellular/cholangiocellular carcinoma (HCC/CCC) with morphological and genetic intratumor heterogeneity. Within the predominant part of the tumor with hepatocellular differentiation, a p.D32V mutation in exon 3 of the CTNNB1 gene occurred concomitantly with a TP53 intron 7/exon 8 splice site mutation.Conclusion
Intratumor heterogeneity challenges the concept of CTNNB1 and TP53 gene mutations being mutually exclusive molecular classifiers in HCC, which has implications for HCC classification approaches.16.
C. Sanfilippo D. Cambria A. Longo M. Palumbo R. Avola M. Pinzone G. Nunnari F. Condorelli G. Musumeci R. Imbesi P. Castogiovanni L. Malaguarnera Michelino Di Rosa 《Inflammation research》2017,66(12):1107-1116
Objective
The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway.Methods
In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14+ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs.Results
Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4+ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1—an antiviral molecule belonging to the genes network—correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels.Conclusions
From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.17.
Background
Bacteria within a biofilm are phenotypically more resistant to antibiotics, desiccation, and the host immune system, making it an important virulence factor for many microbes. Cranberry juice has long been used to prevent infections of the urinary tract, which are often related to biofilm formation. Recent studies have found that the A-type proanthocyanidins from cranberries have anti-biofilm properties against Escherichia coli.Methods
Using crystal violet biofilm staining, resazurin metabolism assays, and confocal imaging, we examined the ability of A-type proanthocyanidins (PACs) to disrupt the biofilm formation of Pseudomonas aeruginosa. We used mass spectrometry to analyze the proteomic effects of PAC treatment. We also performed synergy assays and in vitro and in vivo infections to determine whether PACs, alone and in combination with gentamicin, could contribute to the killing of P. aeruginosa and the survival of cell lines and G. mellonella.Results
Cranberry PACs reduced P. aeruginosa swarming motility. Cranberry PACs significantly disrupted the biofilm formation of P. aeruginosa. Proteomics analysis revealed significantly different proteins expressed following PAC treatment. In addition, we found that PACs potentiated the antibiotic activity of gentamicin in an in vivo model of infection using G. mellonella.Conclusions
Results suggest that A-type proanthocyanidins may be a useful therapeutic against the biofilm-mediated infections caused by P. aeruginosa and should be further tested.18.
Tippaporn Bualeong Sied Kebir Dorothea Hof Lina Goelz Mathias Graewe Stefan Felix Ehrentraut Pascal Knuefermann Georg Baumgarten Rainer Meyer Heidi Ehrentraut 《Journal of negative results in biomedicine》2016,15(1):9
Background
Toll-like receptors (TLRs) are involved in a variety of cardiovascular disorders, including septic cardiomyopathy, ischemia/reperfusion, heart failure, and cardiac hypertrophy. Previous research revealed that TLR4 promotes cardiac hypertrophy in vivo. Therefore, we investigated whether TLR2 is also involved in the development of cardiac hypertrophy.Methods
Tlr2 deficient and wild type mice were subjected to transverse aortic constriction (TAC) or sham operation procedure. Left ventricular, heart and lung weights as well as hemodynamic parameters were determined after 3, 14 or 28 days. Real-time RT PCR was used to evaluate left ventricular gene expression. Protein content was determined via ELISA.Results
TAC increased systolic left ventricular pressure, contraction and relaxations velocities as well as the heart weight in both genotypes. Tlr2 deficiency significantly enhanced cardiac hypertrophy after 14 and 28 days of TAC. Left ventricular end-diastolic pressure and heart rate increased in Tlr2 ?/? TAC mice only. Fourteen days of TAC led to a significant elevation of ANP, BNP, TGFβ and TLR4 mRNA levels in Tlr2 ?/? left ventricular tissue.Conclusion
These data suggest that Tlr2 deficiency may promote the development of cardiac hypertrophy and ventricular remodeling after transverse aortic constriction.19.
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