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.
The mortality risk of coronavirus disease 2019 (COVID-19) is higher in patients with older age, and many elderly patients are reported to require advanced respiratory support.
We reviewed medical ...records of 98 patients aged ≥ 65 years who were hospitalized with COVID-19 during a regional outbreak in Daegu/Gyeongsangbuk-do province of Korea. The outcome measures were in-hospital mortality and the treatment with mechanical ventilation (MV) or high-flow nasal cannula (HFNC).
The median age of the patients was 72 years; 55.1% were female. Most (74.5%) had at least one underlying condition. Overall case fatality rate (CFR) was 20.4%, and median time to death after admission was 8 days. The CFR was 6.1% among patients aged 65-69 years, 22.7% among those aged 70-79 years, and 38.1% among those aged ≥ 80 years. The CFR among patients who required MV was 43.8%, and the proportion of patients received MV/HFNC was 28.6%. Nosocomial acquisition, diabetes, chronic lung diseases, and chronic neurologic diseases were significant risk factors for both death and MV/HFNC. Hypotension, hypoxia, and altered mental status on admission were also associated with poor outcome. CRP > 8.0 mg/dL was strongly associated with MV/HFNC (odds ratio, 26.31; 95% confidence interval, 7.78-88.92;
< 0.001), and showed better diagnostic characteristics compared to commonly used clinical scores.
Patients aged ≥ 80 years had a high risk of requiring MV/HFNC, and mortality among those severe patients was very high. Severe initial presentation and laboratory abnormalities, especially high CRP, were identified as risk factors for mortality and severe hospital course.
Aim
We aimed to evaluate the preventive role of the tyrosine kinase inhibitor dasatinib in an animal model of rheumatoid arthritis (RA).
Methods
DBA/1J mice were injected with bovine type II collagen ...to induce arthritis (collagen‐induced arthritis CIA). There were four experimental groups of mice, namely negative control (non‐CIA), vehicle‐treated CIA, dasatinib‐pretreated CIA, and dasatinib‐treated CIA. After collagen immunization, arthritis progression in the mice was clinically scored twice weekly for 5 weeks. Flow cytometry was used to evaluate in vitro CD4+ T‐cell differentiation and ex vivo mast cell/CD4+ T‐cell differentiation. Osteoclast formation was evaluated using tartrate‐resistant acid phosphatase (TRAP) staining and by estimating the resorption pit area.
Results
We found that the clinical arthritis histological scores were lower in the dasatinib pretreatment group than in the vehicle and dasatinib post‐treatment groups. Flow cytometry showed that FcεR1+ cells were downregulated and regulatory T cells were upregulated in splenocytes of the dasatinib pretreatment group compared with those in the vehicle group. Additionally, there was a decline in IL‐17+ CD4+ T‐cell differentiation and an increase in CD4+ CD24high Foxp3+ T‐cell differentiation with in vitro dasatinib treatment of human CD4+ T cells. The number of TRAP+ osteoclasts and the area of the resorption were decreased in the bone marrow cells derived from dasatinib‐pretreated mice compared with those derived from vehicle group.
Conclusion
Dasatinib protected against arthritis in an animal model of RA by regulating the differentiation of regulatory T cells and IL‐17+ CD4+ T cells and inhibiting osteoclastogenesis, indicating the therapeutic potential of dasatinib in the treatment of early RA.
Burnout is a form of negative emotional and physical response to job stress. This study aimed to investigate the prevalence of burnout among healthcare workers responding to the coronavirus disease ...2019 (COVID-19) outbreak in Korea and to explore correlates of burnout among healthcare workers. A nationwide questionnaire-based survey was conducted from December 1, 2020, to January 29, 2021 on 1425 healthcare workers who worked in one of the 16 healthcare facilities designated for COVID-19 care, in public health centers, or as paramedics in Korea. Burnout was assessed using 16 Korean-adapted items based on the Oldenburg Burnout Inventory (OLBI). Data were collected using a structured questionnaire and analyzed using the R version 4.1.1 software program. OLBI results indicate clinically exhaustion in 84.5% (1204/1425) and clinically disengagement in 91.1% (1298/1425), and 77.3% (1102/1425) met the score criteria for both the exhaustion and disengagement subscales for burnout. Burnout rate was significantly increased in the group with chronic fatigue symptoms (Fatigue Severity Scale ≥ 3.22) after the outbreak of COVID-19 (OR, 3.94; 95% CI 2.80-5.56), in the female group (OR, 2.05; 95% CI 1.46-2.86), in the group with physical symptoms (Patient Health Questionnaire-15 ≥ 10) after the outbreak of COVID-19 (OR, 2.03; 95% CI 1.14-3.60), in the group with a higher Global Assessment of Recent Stress scale (OR, 1.71; 95% CI 1.46-2.01), in the group with post-traumatic stress symptoms (Primary Care Post-Traumatic Stress Disorder-5 ≥ 2) (OR, 1.47; 95% CI 1.08-2.01), and in the younger age group(OR, 1.45; 95% CI 1.22-1.72). The chronic fatigue symptoms were correlated with cumulative days of care (OR, 1.18; 95% CI 1.02-1.37). The physical symptoms were correlated with average contact hours with COVID-19 patients per day (OR, 1.34; 95% CI 1.17-1.54), and cumulative days of care (OR, 1.21; 95% CI 1.06-1.38). Most Korean healthcare workers suffered from burnout related to excessive workload during the COVID-19 pandemic. During a widespread health crisis like COVID-19, it is necessary to regularly check the burnout status in healthcare workers and reduce their excessive workload by supplementing the workforce and providing appropriate working hours sufficient rest hours.
•Recent trends in cell-wall disruption and lipid/astaxanthin extraction are reviewed.•Two industrially important microalgae, Chlorella and Haematococcus are investigated.•Various chemical, ...physico-chemical, and biological methods have been challenged.•Integrative developments based on physiology and cell-wall biology are required.
Recently, biofuels and nutraceuticals produced from microalgae have emerged as major interests, resulting in intensive research of the microalgal biorefinery process. In this paper, recent developments in cell-wall disruption and extraction methods are reviewed, focusing on lipid and astaxanthin production from the biotechnologically important microalgae Chlorella and Haematococcus, respectively. As a common, critical bottleneck for recovery of intracellular components such as lipid and astaxanthin from these microalgae, the composition and structure of rigid, thick cell-walls were analyzed. Various chemical, physical, physico-chemical, and biological methods applied for cell-wall breakage and lipid/astaxanthin extraction from Chlorella and Haematococcus are discussed in detail and compared based on efficiency, energy consumption, type and dosage of solvent, biomass concentration and status (wet/dried), toxicity, scalability, and synergistic combinations. This report could serve as a useful guide to the implementation of practical downstream processes for recovery of valuable products from microalgae including Chlorella and Haematococcus.
Hypoalbuminemia may increase the risk of acute kidney injury (AKI). The authors investigated whether the immediate preoperative administration of 20% albumin solution affects the incidence of AKI ...after off-pump coronary artery bypass surgery.
In this prospective, single-center, randomized, parallel-arm double-blind trial, 220 patients with preoperative serum albumin levels less than 4.0 g/dl were administered 100, 200, or 300 ml of 20% human albumin according to the preoperative serum albumin level (3.5 to 3.9, 3.0 to 3.4, or less than 3.0 g/dl, respectively) or with an equal volume of saline before surgery. The primary outcome measure was AKI incidence after surgery. Postoperative AKI was defined by maximal AKI Network criteria based on creatinine changes.
Patient characteristics and perioperative data except urine output during surgery were similar between the two groups studied, the albumin group and the control group. Urine output (median interquartile range) during surgery was higher in the albumin group (550 ml 315 to 980) than in the control group (370 ml 230 to 670; P = 0.006). The incidence of postoperative AKI in the albumin group was lower than that in the control group (14 13.7% vs. 26 25.7%; P = 0.048). There were no significant between-group differences in severe AKI, including renal replacement therapy, 30-day mortality, and other clinical outcomes. There were no significant adverse events.
Administration of 20% exogenous albumin immediately before surgery increases urine output during surgery and reduces the risk of AKI after off-pump coronary artery bypass surgery in patients with a preoperative serum albumin level of less than 4.0 g/dl.
Objective:
Alzheimer disease (AD) brains are deficient in brain‐derived neurotrophic factor (BDNF), which regulates synaptic plasticity and memory. MicroRNAs (miRNAs) are ∼22‐nucleotide small ...noncoding RNAs that control a variety of physiological and disease processes. Here, we show that miR‐206 regulates BDNF and memory function in AD mice.
Methods:
Expression of miRNAs was analyzed in Tg2576 AD transgenic mice and human AD brain samples. Regulation of BDNF by a selected miRNA was validated by in silico prediction, target gene luciferase assay, and dendritic spine responses in neurons. AM206, a neutralizing inhibitor of miR‐206 (antagomir), was injected into the third ventricle of Tg2576 mice, after which memory function, synaptogenesis, neurogenesis, and target gene expression were assessed. For noninvasive delivery, antagomirs were administered intranasally.
Results:
The brains of Tg2576 mice and the temporal cortex of human AD brains had increased levels of miR‐206. This miRNA targeted BDNF transcripts, and AM206 prevented the detrimental effects of amyloid‐β42 on BDNF and dendritic spine degeneration in Tg2576 neurons. Injection of AM206 into the cerebral ventricles of AD mice increased the brain levels of BDNF and improved their memory function. In parallel, AM206 enhanced the hippocampal synaptic density and neurogenesis. Furthermore, intranasally administered AM206 also reached the brain and increased BDNF levels and memory function in AD mice.
Interpretation:
Our findings demonstrate a novel miRNA‐dependent regulation of BDNF in AD and suggest possible therapeutic approaches, such as noninvasive intranasal delivery of AM206. ANN NEUROL 2012;72:269–277.
(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.
Carbon capture and storage (CCS) technology used for reducing anthropogenic CO2 emissions involves the capture of CO2 from industrial sources and its injection into geological sinks, such as oil ...reservoirs and abandoned gas fields. To ensure environmental and public safety in implementing CCS technology, efficient CO2-monitoring technology must be developed to detect potential CO2 leakage from CCS sites. Conventional CO2 sensors used for monitoring CCS sites are typically high in cost and require professional staff for maintenance. In this study, we developed a portable and low-cost colorimetric CO2 sensor with high soil CO2 detection efficiency for CCS sites. The sensor consists of a detection solution that contains the pH indicator cresol red encapsulated with a gas-permeable membrane. When CO2 enters the sensor through the membrane, the color of the pH indicator changes and this was quantified using an RGB (red, green, blue) application (app), an app that measures the RGB values of a given color. The change in G and B values of the detection solution showed a significant linear relationship with soil CO2 concentration determined via non-dispersive infra-red (NDIR) CO2 sensor (r2 = 0.98, p = 0.001), and thus these values were used for quantification of CO2 concentration. Tests using CO2-injection chamber showed that the optical CO2 sensors can detect soil CO2 concentration of 0.1 to 30% within a few minutes. Field studies conducted at a natural CO2 vent and an artificial CO2 leakage site showed that the optical CO2 sensors can be applied in analyzing surficial CO2 leakage patterns. The advantage of this optical CO2 sensor when applied to field monitoring is that it is inexpensive and has few installation restrictions. Therefore, this optical CO2 sensor has a strong potential for use in monitoring CO2 leakages from CCS sites.
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•A low-cost colorimetric optical sensor for soil CO2 monitoring was developed.•The sensor contains pH indicator and gas-permeable membrane in an acryl reactor.•The color of the sensor is quantified using RGB app.•Low levels of CO2 can be detected with the sensor within a few minutes.•CO2 leakage can be monitored remotely via a mobile phone without power connection.
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.
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