IL-32 plays a contradictory role such as tumor proliferation or suppressor in cancer development depending on the cancer type. In most cancers, it was found that the high expression of IL-32 was associated with more proliferative and progression of cancer. However, studying the isoforms of IL-32 cytokine has placed its paradoxical role into a wide range of functions based on its dominant isoform and surrounding environment. IL-32β, for example, was found mostly in different types of cancer and associated with cancer expansion. This observation is legitimate since cancer exhibits some hypoxic environment and IL-32β was known to be induced under hypoxic conditions. However, IL-32θ interacts directly with protein kinase C-δ reducing NF-κB and STAT3 levels to inhibit epithelial-mesenchymal transition (EMT). This effect could explain the different functions of IL-32 isoforms in cancer. However, pro- or antitumor activity which is dependant on obesity, gender, and age as it relates to IL-32 has yet to be studied. Obesity-related IL-32 regulation indicated the role of IL-32 in cancer metabolism and inflammation. IL-32-specific direction in cancer therapy is difficult to conclude. In this review, we address that the paradoxical effect of IL-32 on cancer is attributed to the dominant isoform, cancer type, tumor microenvironment, and genetic background. IL-32 seems to have a contradictory role in cancer. However, investigating multiple IL-32 isoforms could explain this doubt and bring us closer to using them in therapy.
Providencia rettgeri, belonging to the family Enterobacteriaceae, is a gram negative bacterium. P. rettgeri has been isolated from multiple animal reservoirs, including flies, birds, cats, dogs, cattle, sheep, guinea pigs, and penguins, and are resident oral flora in reptiles such as pythons, vipers, and boas. Providencia species are also found commonly in soil, waters and, therefore, seems to be widely distributed in nature. P rettgeri has been isolated in crocodiles with meningitis/septicemia and in chickens with enteritis.
In humans, P. rettgeri is associated with hospital acquired infections, including catheter-related urinary tract infections, bacteremia, skin infections, diarrhea, and gastroenteritis. A case report found P. rettgeri to be a cause of ocular infections, including keratitis, conjunctivitis, and endophthalmitis.
Automated identification systems that use biochemical reactions are known to accurately identify Enterobacteriaceae species. However, the accurate identification of some Enterobacteriaceae by the automated identification systems may be problematic because of their inconsistent biochemical profiles. There are some reports of misidentification of Providentia stuartii by commercial system, but there is no report for P. rettgeri. In this study, we report the case of P. rettgeri misidentified as E. coli with VITEK 2 system from patients with sepsis due to complicated urinary tract infection.
Case Report
A 77-year-old female patient admitted with drowsy mental status. She was suffering from hypertension and diabetes for 35 years, and had a history of cystostomy due to neurogenic bladder six years ago. She was diagnosed with Parkinson’s disease and bedridden for 1 year.
At admission, her body temperature, pulse, respiration rate, and blood pressure were 38.2?, 106/min, 24/min, and 66/45mmHg, respectively. Her complete blood count showed that white blood cell count was 31,000/μL (absolute neutrophil count 30,300/μL) and platelet count was 178,000/μL. The values of C-reactive protein and procalcitonin were 21.24 mg/dL and 188.51 ng/mL, respectively. Two sets of blood cultures and one urine culture were obtained before administration of antibiotics. After 24-hour incubation of blood culture bottles, gram negative rods were detected, subculture showed non-hemolytic grayish colonies on blood agar and colorless colonies on MacConkey agar.
The VITEK 2 Gram-negative (GN) identification card (bioMerieux, Marcy l’Etoile, France) was used to identify the strain. The VITEK 2 system identified this strain as E. coli with an ambiguous confidence level (85% probability). The same result was obtained when the GN card was repeated. Additional biochemical tests showed urease positive and alkaline slant/acidic butt with gas production for triple sugar iron test. In addition, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was conducted by Bruker Biotyper (Bruker Daltonics, Leipzig, Germany) and we could obtain result of P. rettgeri. The sequence analysis of 16S rRNA gene confirmed P. rettgeri (Genbank: NR042413.1).
Antimicrobial susceptibility testing was performed by using VITEK 2 system. This strain was resistant to ertapenem and imipenem. Further, modified Hodge test was negative and carbapenemase inhibition test was positive for phenylboronic acid positive but negative for ethylenediaminetetraacetic acid. PCRs for five carbapenemase-encoding genes (NDM-1, KPC, VIM, IMP, GES and OXA-48) were all negative.
In spite of administration of antibiotics and supportive care, she expired due to heart failure 29 days after admission.
Discussion
P. rettgeri is in the genus Providencia, along with P. stuartii, Providencia alcalifaciens, Providencia heimbachae, and Providencia rustigianii. The first species of the genus now known as Providencia was isolated by Rettger in 1904. However, the bacterium was not submitted to detailed study until 14 years later, when it was further characterized and named Bacterium rettgeri by Hadley et al. Then, Kauffmann first proposed the genus name Providencia in 1952.
In this case, two biochemical test results of the VITEK 2 GN card (negative for adonitol fermentation and citrate utilization) varied between the current strain and previously identified P. rettgeri strains. It was demonstrated that nearly 0% of P. rettgeri is negative for adonitol fermentation, whereas 95% of E. coli is negative for the adonitol fermentation. Moreover, it was demonstrated that 4-5% of P. rettgeri is negative for citrate utilization, whereas 99% of E. coli is negative for the citrate utilization. The infrequent negative results for adonitol fermentation and citrate utilization may mislead the GN card to misidentify P. rettgeri as E. coli. This shows that we have to be aware of the limits on the automated VITEK 2 system to identify some strains which have variable biological characteristics.
Providencia infections are uncommon and are usually nosocomial. They represent an emerging problem because of the increasing prevalence of antibiotic resistance secondary to extended-spectrum beta-lactamase (ESBL). Many Providencia isolates are resistant to numerous antibiotics. However, according to the knowledges about the antibiotic susceptibility, P. rettgeri strains are less resistant than other Providencia strains to aminoglycosides, cephalosporins and substituted penicillins. On the other hand, multi-resistant P. rettgeri strains and carbapenem-resistant P. rettgeri strain were also described. While carbapenem-resistant Enterobacteriaceae (CRE) remained uncommon in our health care system, the frequency of CRE increased. In this case, the strain was resistant to carbapenem and this is the first report of CRE of P. rettgeri in Korea. However, we failed to identify carbapenem resistance mechanism.
In summary, we report the case of P. rettgeri, which was not exactly identified by automated identification system that use biochemical reactions but confirmed by MALDI-TOF analysis and 16s rRNA gene sequence analysis. Based on sign from milestone clinical trials, ablation is safe and effective for treating Hepatitis, with virtually no risk of death. The results in the real world may be somewhat different, based upon the recent findings. According to the experts the mortality rates among 60,203 hepatitis after suffering catheter ablation between 2010 and 2015. The education included patients from through the country who were treated at a variety of medical centers, rather than the large academic centers that are normally included in clinical trials.
The increasing burden of cardiovascular disorders will intensify the demand for heart arrhythmia monitoring devices in the coming years. The occurrence of various cardiac dysrhythmias includes atrial flutter, bradycardia, Atrial Fibrillation between others is rising at a quick pace. According to the Public Health England, approx. 1.4 million people are suffering from atrial fibrillation, alongside with number of undiagnosed cases of the disease.
This type of heart condition needs timely and precise observing of the heart rhythm, in that way it boost up the adoption of cardiac arrhythmia monitoring devices over the estimate years. The Worldwide Heart Arrhythmia Market Analysis will spread over USD 8.0 billion by 2025. Growth of telemetric and mobile Hepatitis monitoring solutions will impel the global cardiac arrhythmia monitoring devices market growth in the forthcoming years.
IL-18 binding protein (IL-18BP) was originally discovered in 1999 while attempting to identify an IL-18 receptor ligand binding chain (also known as IL-18Rα) by subjecting concentrated human urine to an IL-18 ligand affinity column. The IL-18 ligand chromatography purified molecule was analyzed by protein microsequencing. The result revealed a novel 40 amino acid polypeptide. To isolate the complete open reading frame (ORF), various human and mouse cDNA libraries were screened using cDNA probe derived from the novel IL-18 affinity column bound molecule. The identified entire ORF gene was thought to be an IL-18Rα gene. However, IL-18BP has been proven to be a unique soluble antagonist that shares homology with a variety of viral proteins that are distinct from the IL-18Rα and IL-18Rβ chains. The IL-18BP cDNA was used to generate recombinant IL-18BP (rIL-18BP), which was indispensable for characterizing the role of IL-18BP
Abstract Background Alpha-1 antitrypsin (AAT) is a major serine protease inhibitor. AAT deficiency (AATD) is a genetic disorder characterized by early-onset severe emphysema. In well-selected AATD patients, therapy with plasma-derived AAT (pAAT), “augmentation therapy”, provides modest clinical improvement but is perceived as cumbersome with weekly intravenous infusions. Using mouse models of emphysema, we compared the effects of a recombinant AAT-IgG1 Fc-fusion protein (AAT-Fc), which is expected to have a longer half-life following infusion, to those of pAAT. Methods In an elastase model of emphysema, mice received a single intratracheal instillation of porcine pancreatic elastase (PPE) or human leucocyte elastase (hLE). AAT-Fc, pAAT, or vehicle was administered intraperitoneally 1 day prior to or 3 weeks following elastase instillation. Lung function and histology assessments were performed at 7 and 32 days after elastase instillation. In a cigarette smoke (CS) model of emphysema, mice were exposed to CS daily, 5 days a week, for 6 months and AAT-Fc, pAAT, or vehicle were administered every 10 days during the last 3 months of CS exposure. Assessments were performed 3 days after the last CS exposure. Immune responses to lung elastin peptide (EP) and the effects of AAT-Fc or pAAT treatment on dendritic cell (DC) function were determined ex vivo. Results Both elastase instillation and CS exposure triggered emphysema-like alveolar enlargement, increased lung compliance, and increased markers of inflammation compared to controls. Administration of AAT-Fc either prior to or following elastase instillation or during CS exposure provided greater protection than pAAT against alveolar enlargement, lung dysfunction, and airway inflammation. When challenged ex vivo with EP, spleen mononuclear cells from elastase-exposed mice exhibited dose-dependent production of IFNγ and IL-17, suggesting immune reactivity. In co-culture experiments with splenic CD4 + T cells isolated from elastase-exposed mice, AAT-Fc treatment prior to EP-priming of bone marrow-derived dendritic cells inhibited the production of IFNγ and IL-17. Conclusions Compared to pAAT, AAT-Fc more effectively prevented or attenuated elastase- and CS-induced models of emphysema. These effects were associated with immunomodulatory effects on DC activity. AAT-Fc may provide a therapeutic option to individuals with AATD- and CS-induced emphysema.
Background The incidence of fungal infections varies among hospitals and between different time periods. We performed a nationwide survey in Korea to in-vestigate the distribution of yeast and mold species recovered from clinical specimens. Methods The distributions of clinical isolates of yeast and mold species obtained from 12 university hospitals between January and December 2011 were evaluated relative to the hospital and specimen type. Results A total of 39,533 fungal isolates (37,847 yeast and 1,686 mold isolates) were obtained. C. albicans was the predominant species (49.4%) among the yeast isolates from all clinical specimens, followed by C. glabrata (7.2%) and C. tropicalis (6.5%). For 5,248 yeast isolates from sterile body fluids, blood was the most common source of yeasts (71.1%), followed by peritoneal fluid (9.4%). Although C. albicans was the predominant species at all but two hospitals, the rate of non-albicans Candida species varied from 71.2% to 40.1%, depending on the hospital. The yeast species recovered most fre-quently from the sterile body fluids was C. albicans (41.7%), followed by C. parapsilosis (17.8%) and C. glabrata (14.4%), while that from non-sterile sites was C. albicans (50.7%), followed by C. glabrata (6.0%) and C. tropicalis (5.5%). For mold-forming fungi, Aspergillus species (62.3%) were most common, followed by Trichophyton species (15.4%). Respiratory specimens were the most common source of molds (39.6%), followed by abscesses/wounds (28.4%) and tissues (17.5%). Conclusion The rank order of distribution for different fungal species varied among hospitals and specimen types. Continual national surveillance programs are essential for identifying possible changes in fungal infection patterns.
Abstract BackgroundAlpha-1 antitrypsin (AAT) is a major serine protease inhibitor. AAT deficiency (AATD) is a genetic disorder characterized by early-onset severe emphysema. In well-selected AATD patients, therapy with plasma-derived AAT (pAAT), “augmentation therapy”, provides modest clinical improvement but is perceived as cumbersome with weekly intravenous infusions. Using mouse models of emphysema, we compared the effects of a recombinant AAT-IgG1 Fc-fusion protein (AAT-Fc), which is expected to have a longer half-life following infusion, to those of pAAT. MethodsIn an elastase model of emphysema, mice received a single intratracheal instillation of porcine pancreatic elastase (PPE) or human leucocyte elastase (hLE). AAT-Fc, pAAT, or vehicle was administered intraperitoneally 1 day prior to or 3 weeks following elastase instillation. Lung function and histology assessments were performed at 7 and 32 days after elastase instillation. In a cigarette smoke (CS) model of emphysema, mice were exposed to CS daily, 5 days a week, for 6 months and AAT-Fc, pAAT, or vehicle were administered every 10 days during the last 3 months of CS exposure. Assessments were performed 3 days after the last CS exposure. Immune responses to lung elastin peptide (EP) and the effects of AAT-Fc or pAAT treatment on dendritic cell (DC) function were determined ex vivo . ResultsBoth elastase instillation and CS exposure triggered emphysema-like alveolar enlargement, increased lung compliance, and increased markers of inflammation compared to controls. Administration of AAT-Fc either prior to or following elastase instillation or during CS exposure provided greater protection than pAAT against alveolar enlargement, lung dysfunction, and airway inflammation. When challenged ex vivo with EP, spleen mononuclear cells from elastase-exposed mice exhibited dose-dependent production of IFNg and IL-17, suggesting immune reactivity. In co-culture experiments with splenic CD4 + T cells isolated from elastase-exposed mice, AAT-Fc treatment prior to EP-priming of bone marrow-derived dendritic cells inhibited the production of IFNg and IL-17. ConclusionsCompared to pAAT, AAT-Fc more effectively prevented or attenuated elastase- and CS-induced models of emphysema. These effects were associated with immunomodulatory effects on DC activity. AAT-Fc may provide a therapeutic option to individuals with AATD- and CS-induced emphysema.
Although it has been established that diabetes increases susceptibility to infections, the role of insulin (INS) in the immune response is unknown. Here, we investigated the immunological function of INS. Proinsulin dimer (pINSd) was a potent immune stimulus that induced inflammatory cytokines, but mature INS was unable to induce an immune response. An affinity-purified rabbit polyclonal antibody raised against mature IL-1α recognized IL-1α and pINS but failed to detect mature INS and IL-1β. Analysis of the pINS sequence revealed the existence of an INS/IL-1α motif in the C-peptide of pINS. Surprisingly, the INS/IL-1α motif was recognized by monoclonal antibody raised against IL-1α. Deleting the INS/IL-1α motif in pINSd and IL-1α changed their activities. To investigate the pINSd receptor, the reconstitution of IL-1 receptor 1 (IL-1R1) in Wish cells restored pINSd activity that was reversed by an IL-1R antagonist. These data suggested that pINSd needs IL-1R1 for inflammatory cytokine induction. Mouse embryo fibroblast cells of IL-1R1-deficient mice further confirmed that pINSd promotes immune responses through IL-1R1.
IL-32 acts as a pro-inflammatory cytokine by inducing the synthesis of inflammatory molecules as well as promoting the morphological changes involved in the transformation of monocytes into osteoclasts (OCs).Evaluation of the functions of IL-32 has mainly focused on its inflammatory properties, such as involvement in the pathogenesis of various autoimmune diseases.Recently, IL-32 was shown to be involved in bone metabolism, in which it promotes the differentiation and activation of OCs and plays a key role in bone resorption in inflammatory conditions.IL-32γ also regulates bone formation in conditions such as ankylosing spondylitis and osteoporosis.In this review, we summarize the results of recent studies on the role of IL-32γ in bone metabolism in inflammatory arthritis.
Abstract Interleukin-32 gamma (IL-32γ) is a recently discovered cytokine that is elevated in inflamed tissues and contributes to pathogenic features of bone in human inflammatory rheumatic diseases. Nevertheless, the role of IL-32γ and its direct involvement in bone metabolism is unclear. We investigated the molecular mechanism of IL-32γ in bone remodeling and the hypothetical correlation between IL-32γ and disease activity in osteoporosis patients. Transgenic (TG) mice overexpressing human IL-32γ showed reduced bone loss with advancing age, increased bone formation, and high osteogenic capacity of osteoblast compared to wild-type (WT) mice through the upregulation of miR-29a, which caused a reduction of Dickkopf-1 (DKK1) expression. IL-32γ TG mice were protected against ovariectomy (OVX)induced osteoporosis compared with WT mice. Decreased plasma IL-32γ levels were associated with bone mineral density (BMD) in human patients linked to increased DKK1 levels. These results indicate that IL-32γ plays a protective role for bone loss, providing clinical evidence of a negative correlation between IL-32γ and DKK1 as bone metabolic markers.
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