Problem
Chorioamnionitis is caused by a bacterial infection that ascends from the vagina and can cause adverse pregnancy outcomes (APOs). Fusobacterium nucleatum (F. nucleatum) is a periodontal ...pathogen associated with the occurrence of APOs. In this study, we evaluated whether receptor‐interacting protein kinase 2 (Ripk2), an adaptor protein of the cytosolic receptors nucleotide‐binding oligomerization domain (NOD)1 and NOD2, in macrophages and human decidual stromal cells (hDSCs) contributes to immune responses against F. nucleatum.
Method of Study
Bone marrow‐derived macrophages (BMDMs) isolated from wild‐type (WT) and Ripk2‐deficient mice and hDSCs were cultured with F. nucleatum (MOI 1, 10, 100). BMDMs and hDSCs were assessed using enzyme‐linked immunosorbent assay, Western blot analysis, real‐time PCR, and nitrite assay.
Results
Fusobacterium nucleatum‐induced production of IL‐6, but not of TNF‐α and IL‐10, was lower in Ripk2‐deficient BMDMs than in WT cells. Western blotting revealed a decrease in F. nucleatum‐induced p65 phosphorylation in Ripk2‐deficient macrophages, whereas mitogen‐activated protein kinases activation was comparable between WT and Ripk2‐deficient cells. The production of nitric oxide (NO) in response to F. nucleatum and the gene and protein expression of inducible NO synthase was impaired in Ripk2‐deficient BMDMs. In hDSCs, F. nucleatum upregulated the gene and protein expression of NOD1, NOD2, and Ripk2 in a time‐dependent manner. F. nucleatum also increased the production of IL‐6, CXCL8, and CCL2, whereas this production was decreased by the Ripk2 inhibitors SB203580 and PP2.
Conclusions
In conclusion, Ripk2 signaling appears to contribute to the F. nucleatum‐induced immune response and can be a preventive and therapeutic target against APOs.
Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and its incidence is steadily increasing. IBD is closely related to the intestinal microbiota, and probiotics are known ...to be a potential therapeutic agent for IBD. In our study, we evaluated the protective effect of
CVL-001, isolated from
kimchi, on dextran sulfated sodium (DSS)-induced colitis in mice. The oral administration of
CVL-001 according to the experimental schedule alleviated weight loss and disease activity in the mice with colitis. Furthermore, the length and histopathology of the colon improved. The expression of tumor necrosis factor (
)
and interleukin
genes decreased in the colons of mice that were administered
CVL-001, whereas that of
increased. The expressions of genes coding for E-cadherin, claudin3, occludin, and mucin were also restored. In co-housed conditions,
CVL-001 administration did not improve disease activity, colon length, and histopathology. Microbiota analysis revealed that
CVL-001 administration increased the abundance of microbiota and altered
/
ratio, and decreased
. In conclusion,
CVL-001 administration protects mice from DSS-induced colitis by regulating immune response and intestinal integrity via gut microbiota modulation.
(MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons ...(IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-β treatment reduced the intracellular growth of MAB in macrophages. Deficiency of IFN-α/β receptor (IFNAR) led to the reduction of nitric oxide (NO) production in MAB-infected macrophages. Consistently, rIFN-β treatment enhanced the expression of iNOS gene and protein, and NO production in response to MAB. We also found that NO is essential for the intracellular growth control of MAB within macrophages in an inhibitor assay using iNOS-deficient cells. In addition, pretreatment of rIFN-β before MAB infection in mice increased production of NO in the lungs at day 1 after infection and promoted the bacterial clearance at day 5. However, when alveolar macrophages were depleted by treatment of clodronate liposome, rIFN-β did not promote the bacterial clearance in the lungs. Moreover, we found that a cytosolic receptor nucleotide-binding oligomerization domain 2 (NOD2) is required for MAB-induced TANK binding kinase 1 (TBK1) phosphorylation and IFN-β gene expression in macrophages. Finally, increase in the bacterial loads caused by reduction of NO levels was reversed by rIFN-β treatment in the lungs of NOD2-deficient mice. Collectively, our findings suggest that type I IFNs act as an intermediator of NOD2-induced NO production in macrophages and thus contribute to host defense against MAB infection.
Summary Background In 2015, a large outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection occurred following a single patient exposure in an emergency room at the Samsung ...Medical Center, a tertiary-care hospital in Seoul, South Korea. We aimed to investigate the epidemiology of MERS-CoV outbreak in our hospital. Methods We identified all patients and health-care workers who had been in the emergency room with the index case between May 27 and May 29, 2015. Patients were categorised on the basis of their exposure in the emergency room: in the same zone as the index case (group A), in different zones except for overlap at the registration area or the radiology suite (group B), and in different zones (group C). We documented cases of MERS-CoV infection, confirmed by real-time PCR testing of sputum samples. We analysed attack rates, incubation periods of the virus, and risk factors for transmission. Findings 675 patients and 218 health-care workers were identified as contacts. MERS-CoV infection was confirmed in 82 individuals (33 patients, eight health-care workers, and 41 visitors). The attack rate was highest in group A (20% 23/117 vs 5% 3/58 in group B vs 1% 4/500 in group C; p<0·0001), and was 2% (5/218) in health-care workers. After excluding nine cases (because of inability to determine the date of symptom onset in six cases and lack of data from three visitors), the median incubation period was 7 days (range 2–17, IQR 5–10). The median incubation period was significantly shorter in group A than in group C (5 days IQR 4–8 vs 11 days 6–12; p<0·0001). There were no confirmed cases in patients and visitors who visited the emergency room on May 29 and who were exposed only to potentially contaminated environment without direct contact with the index case. The main risk factor for transmission of MERS-CoV was the location of exposure. Interpretation Our results showed increased transmission potential of MERS-CoV from a single patient in an overcrowded emergency room and provide compelling evidence that health-care facilities worldwide need to be prepared for emerging infectious diseases. Funding None.
Background
This study aims to investigate the noninferiority of Enhanced Recovery After Surgery (ERAS) for pancreaticoduodenectomy (PD).
Methods
In this single‐center trial, we randomly assigned 276 ...adult patients who underwent open PD into ERAS and conventional groups with 138 patients in each, from 2015 through 2017. The primary endpoint was the incidence of overall morbidity until postoperative 3 months. The secondary endpoints were in‐hospital or 30‐day mortality, postoperative length of stay (LOS), nutritional status and overall hospital costs.
Results
Overall morbidity was reported in 64 patients (52.0%, ERAS group) and in 68 patients (54.8%, conventional group) (risk difference RD −2.81 percentage points (pp); 90% two‐sided confidence interval −13.24 to 7.63). Mortality did not occur in any patients. The two groups did not differ significantly in median postoperative LOS (both 11 days; RD −8.46 pp), body mass index (22.4 ± 2.75 vs. 22.4 ± 2.65 kg/m2; RD −3.48 pp), Patient‐Generated Subjective Global Assessment score over 4 (45 40.5% vs. 50 43.1% patients; RD −2.56 pp), and median overall hospital cost (15.61 vs. 16.04, ×106 KRW; RD −6.08 pp).
Conclusions
Even in PD, modified ERAS protocol was not inferior to conventional protocol, while reducing treatment burden.
Highlight
This randomized clinical trial by Hwang and colleagues revealed that the Enhanced Recovery After Surgery (ERAS) protocol was not inferior to the conventional perioperative management protocol for pancreaticoduodenectomy regarding morbidity, mortality, length of stay and hospital cost. The ERAS protocol not only reduces treatment burden, but also facilitates treatment administration.
While most NOD‐like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of ...NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein–Barr virus (EBV) and murine gammaherpesvirus 68 (MHV‐68), establish latent infection in B lymphocytes, which requires elevated NF‐κB. This study shows that during latent EBV infection of human B cells, viral‐encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1‐induced‐NF‐κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF‐κB activation by promoting the degradation of LMP1 in a proteasome‐dependent manner. In vivo, MHV‐68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3‐deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis.
Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the ...disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC).
Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC
and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites.
The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC.
Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.
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Obesity is a globally widespread metabolic disorder, characterized by immoderate fat accumulation in the body. There are different types of body fats such as white adipose tissue ...(WAT), which stores surplus energy in the body, and brown adipose tissue (BAT) which utilize energy to produce heat during metabolism. BAT acts many beneficial functions in metabolic disorders including type 2 diabetes and obesity. Recent studies have investigated methods for promoting the fat browning process of WAT in obesity because of various reasons such as the improvement of insulin resistance, and weight loss. Among natural polyphenolic compounds, resveratrol has been highlighted due to its anti-oxidant and anti-obesity as well as anti-inflammation and anti-cancer properties. Recent studies have paid a lot of attention to that resveratrol may act as a fat browning activator, involved in the secretion of many myokines and adipokines. Here, we reviewed the role of resveratrol in fat browning and also the association between resveratrol and adipokines/myokines in the fat browning process. Our review may provide novel insight into the role of resveratrol in fat browning, leading to the maintenance of a healthy weight against obesity.
A Newcastle disease virus (NDV)-vectored vaccine expressing clade 2.3.4.4b H5 Hemagglutinin was developed and assessed for efficacy against H5N1 highly pathogenic avian influenza (HPAI) in specific ...pathogen-free (SPF) chickens, broilers, and domestic ducks. In SPF chickens, the live recombinant NDV-vectored vaccine, rK148/22-H5, achieved complete survival against HPAI and NDV challenges and significantly reduced viral shedding. Notably, the live rK148/22-H5 vaccine conferred good clinical protection in broilers despite the presence of maternally derived antibodies. Good clinical protection was observed in domestic ducks, with decreased viral shedding. It demonstrated complete survival and reduced cloacal viral shedding when used as an inactivated vaccine from SPF chickens. The rK148/22-H5 vaccine is potentially a viable and supportive option for biosecurity measure, effectively protecting in chickens against the deadly clade 2.3.4.4b H5 HPAI and NDV infections. Furthermore, it aligns with the strategy of Differentiating Infected from Vaccinated Animals (DIVA).
Although hypoalbuminemia is a known risk factor for acute kidney injury (AKI) following surgery, little is known about its effects following aneurysm clipping surgery. We aimed to investigate the ...predictors of AKI and overall mortality and assessed the relationship between preoperative albumin and postoperative outcomes after aneurysm clipping surgery.
This study included 2,339 patients who underwent aneurysm clipping surgery. According to the criteria updated by the Kidney Disease: Improving Global Outcomes (KDIGO), patients were classified into AKI and no AKI group. Independent AKI predictors were analyzed by multivariate methods, and the influence of AKI on the outcome variables was assessed with by propensity score matching analysis. Survival in relation to AKI was analyzed using the Kaplan-Meier method.
The total proportion of patients who developed AKI was 1.9%. The cutoff value of preoperative albumin for predicting AKI was 3.9 g/dL. Multivariate analyses showed that preoperative albumin≤ 3.9 g/dL, aneurysmal subarachnoid hemorrhage, male sex, phenylephrine use, and hemoglobin were associated with postoperative AKI development. In multivariate analysis, mortality was increased in AKI patients (p< 0.01). After propensity score matching, preoperative albumin≤ 3.9 g/dL was significantly related to AKI and overall mortality.
Preoperative albumin≤ 3.9 g/dL is associated with postoperative AKI and mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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