GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Comparison of Macrophage Immune Responses and Metabolic Reprogramming in Smooth and Rough Variant Infections of Mycobacterium mucogenicum
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 5 ( 2022-02-24), p. 2488-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 5 ( 2022-02-24), p. 2488-
    Abstract: Mycobacterium mucogenicum (Mmuc), a rapidly growing nontuberculous mycobacterium (NTM), can infect humans (posttraumatic wound infections and catheter-related sepsis). Similar to other NTM species, Mmuc exhibits colony morphologies of rough (Mmuc-R) and smooth (Mmuc-S) types. Although there are several case reports on Mmuc infection, no experimental evidence supports that the R-type is more virulent. In addition, the immune response and metabolic reprogramming of Mmuc have not been studied on the basis of morphological characteristics. Thus, a standard ATCC Mmuc strain and two clinical strains were analyzed, and macrophages were generated from mouse bone marrow. Cytokines and cell death were measured by ELISA and FACS, respectively. Mitochondrial respiration and glycolytic changes were measured by XF seahorse. Higher numbers of intracellular bacteria were found in Mmuc-R-infected macrophages than in Mmuc-S-infected macrophages. Additionally, Mmuc-R induced higher levels of the cytokines TNF-α, IL-6, IL-12p40, and IL-10 and induced more BMDM necrotic death. Furthermore, our metabolic data showed marked glycolytic and respiratory differences between the control and each type of Mmuc infection, and changes in these parameters significantly promoted glucose metabolism, extracellular acidification, and oxygen consumption in BMDMs. In conclusion, at least in the strains we tested, Mmuc-R is more virulent, induces a stronger immune response, and shifts bioenergetic metabolism more extensively than the S-type. This study is the first to report differential immune responses and metabolic reprogramming after Mmuc infection and might provide a fundamental basis for additional studies on Mmuc pathogenesis.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23052488
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Aconitate Decarboxylase 1 Deficiency Exacerbates Mouse Colitis Induced by Dextran Sodium Sulfate
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 8 ( 2022-04-15), p. 4392-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 8 ( 2022-04-15), p. 4392-
    Abstract: Ulcerative colitis is a complex inflammatory bowel disorder disease that can induce rectal and colonic dysfunction. Although the prevalence of IBD in Western countries is almost 0.5% of the general population, genetic causes are still not fully understood. In a recent discovery, itaconate was found to function as an immune-modulating metabolite in mammalian immune cells, wherein it is synthesized as an antimicrobial compound from the citric acid cycle intermediate cis-aconitic acid. However, the association between the Acod1 (Aconitate decarboxylase 1)-itaconate axis and ulcerative colitis has rarely been studied. To elucidate this, we established a DSS-induced colitis model with Acod1-deficient mice and then measured the mouse body weights, colon lengths, histological changes, and cytokines/chemokines in the colon. We first confirmed the upregulation of Acod1 RNA and protein expression levels in DSS-induced colitis. Then, we found that colitis symptoms, including weight loss, the disease activity index, and colon shortening, were worsened by the depletion of Acod1. In addition, the extent of intestinal epithelial barrier breakdown, the extent of immune cell infiltration, and the expression of proinflammatory cytokines and chemokines in Acod1-deficient mice were higher than those in wild-type mice. Finally, we confirmed that 4-octyl itaconate (4-OI) alleviated DSS-induced colitis in Acod1-deficient mice and decreased the expression of inflammatory cytokines and chemokines. To our knowledge, this study is the first to elucidate the role of the Acod1-itaconate axis in colitis. Our data clearly showed that Acod1 deletion resulted in severe DSS-induced colitis and substantial increases in inflammatory cytokine and chemokine levels. Our results suggest that Acod1 may normally play an important regulatory role in the pathogenesis of colitis, demonstrating the potential for novel therapies using 4-OI.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23084392
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Diagnostic Evaluation and Preparation of the Reference Information for River Restoration in South Korea
    MDPI AG ; 2021
    In:  International Journal of Environmental Research and Public Health Vol. 18, No. 4 ( 2021-02-10), p. 1724-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 4 ( 2021-02-10), p. 1724-
    Abstract: We assessed the naturalness of rivers based on the riparian vegetation index throughout the national territory of South Korea as a preparatory process for restoration to improve the ecological quality of rivers. The riparian vegetation index was obtained by incorporating the diversity of species and community, vegetation profile, and ratios of the number of species and areas occupied by exotic, obligate upland, and annual plants. The evaluation was conducted based on both the riparian vegetation index and each vegetation component. The result of the evaluation based on the riparian vegetation index showed that more than 70% of the river reaches were graded as less than “moderate” and exotic and obligate upland plants were more common than endemic aquatic plants. The reaches recorded as “very good” and “good” grades were usually restricted around the upstream of the north and central-eastern parts, whereas reaches of the other areas showed “poor” naturalness (less than “moderate”). The vegetation components selected for the evaluation showed a significant correlation with each other as well as the riparian vegetation index. The degree of contribution of each vegetation component showed that the vegetation profile played the most significant role, followed by species diversity, community diversity, and the ratio of area occupied by annual plants. The riparian vegetation index revealed a significant correlation with the indices based on other taxa such as benthic invertebrates, periphytic algae, and fish, habitat conditions in the waterway, and water quality based on biochemical oxygen demand (BOD). The diagnostic evaluation results imply that most reaches need ecological restoration. The reference information was prepared by incorporating the vegetation condition with the highest score in each reach in the diagnostic evaluation. The river reach was divided into five reaches of upper and lower valley streams, upstream, midstream, and downstream. Information on the reference vegetation for restoration was prepared with the stand profile including both horizontal and vertical arrangements of riparian vegetation and species composition classified by the reach divided into five types. The levels of restoration were determined based on the diagnostic evaluation results. The lower the naturalness grade, the higher the level of restorative treatment was recommended.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph18041724
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2175195-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    The Need of Enterococcal Coverage in Severe Intra-Abdominal Infection: Evidence from Animal Study
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 5 ( 2021-03-02), p. 1027-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 5 ( 2021-03-02), p. 1027-
    Abstract: Intra-abdominal infection (IAI) is a common and important cause of infectious mortality in intensive care units. Adequate source control and appropriate antimicrobial regimens are key in the management of IAI. In community-acquired IAI, guidelines recommend the use of different antimicrobial regimens according to severity. However, the evidence for this is weak. We investigated the effect of enterococcal coverage in antimicrobial regimens in a severe polymicrobial IAI model. We investigated the effects of imipenem/cilastatin (IMP) and ceftriaxone with metronidazole (CTX+M) in a rat model of severe IAI. We observed the survival rate and bacterial clearance rate. We identified the bacteria in blood culture. We measured lactate, alanine aminotransferase (ALT), creatinine, interleukin (IL)-6, IL-10, and reactive oxygen species (ROS) in the blood. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) was also estimated to determine the level of immune suppression. In the severe IAI model, IMP improved survival and bacterial clearance compared to CTX+M. Enterococcus spp. were more frequently isolated in the CTX+M group. IMP also decreased plasma lactate, cytokine, and ROS levels. ALT and creatinine levels were lower in IMP group. In the mild-to-moderate IAI model, however, there was no survival difference between the groups. Immune suppression of PBMCs was observed in IAI model, and it was more prominent in the severe IAI model. Compared to CTX+M, IMP improved the outcome of rats in severe IAI model.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10051027
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Clinical Associations between Serial Electrocardiography Measurements and Sudden Cardiac Death in Patients with End-Stage Renal Disease Undergoing Hemodialysis
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 9 ( 2021-04-29), p. 1933-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 9 ( 2021-04-29), p. 1933-
    Abstract: The rate of sudden cardiac death (SCD) for hemodialysis (HD) patients is significantly higher than that observed in the general population and have the highest risk for arrhythmogenic death. In this multi-center study, patients starting hemodialysis in each hospital were enrolled; they underwent regular check-ups in an open-patient clinic. We examined serial electrocardiography (ECG) data in patients undergoing HD and determined their associations with the occurrence of SCD. Of 678 enrolled subjects who underwent serial ECG before and after hemodialysis, 291 died and 39 developed SCD. In all subjects, the QT peak-to-end (QTpe) interval at all leads and QRS duration were shortened after hemodialysis. The SCD group showed a significant change in the QTpe interval of the inferior, anterior, and lateral leads before and after hemodialysis compared with the survivor group (p 〈 0.001). In the pre-hemodialysis ECG, SCD patients had significantly longer QTpe intervals in all leads (p 〈 0.001) and a longer QRS duration (92.6 ± 14.0 vs. 100.6 ± 14.9 ms, p = 0.015) than survivors. In conclusion, patients with a longer QTpe interval before hemodialysis and large changes in ECG parameters after hemodialysis might be at a higher risk of SCD. Therefore, changes in the ECG before and after hemodialysis could help to predict SCD.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10091933
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Serial Change of Endotoxin Tolerance in a Polymicrobial Sepsis Model
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 12 ( 2022-06-13), p. 6581-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 12 ( 2022-06-13), p. 6581-
    Abstract: Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2′,7′-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23126581
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Verbascoside-Rich Abeliophyllum distichum Nakai Leaf Extracts Prevent LPS-Induced Preterm Birth Through Inhibiting the Expression of Proinflammatory Cytokines from Macrophages and the Cell Death of Trophoblasts Induced by TNF-α
    MDPI AG ; 2020
    In:  Molecules Vol. 25, No. 19 ( 2020-10-07), p. 4579-
    Details
    In: Molecules, MDPI AG, Vol. 25, No. 19 ( 2020-10-07), p. 4579-
    Abstract: Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules25194579
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Dual Inhibition of P-gp and BCRP Improves Oral Topotecan Bioavailability in Rodents
    MDPI AG ; 2021
    In:  Pharmaceutics Vol. 13, No. 4 ( 2021-04-15), p. 559-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 4 ( 2021-04-15), p. 559-
    Abstract: P-glycoprotein (P-gp) inhibition has been studied to overcome multidrug resistance in cancer chemotherapy but failed in clinical trials due to low/toxic effects. Recently, a dual modulation of transporters and natural derivatives have been examined to surmount this limitation. We examined breast cancer resistance protein (BCRP) inhibition in vitro and in vivo by P-gp inhibitors derived from natural compounds in previous studies. P-gp inhibitors increased the accumulation of the anticancer drug, topotecan (TPT)—a substrate of P-gp and BCRP, albeit with higher affinity for BCRP—in BCRP-overexpressing cells, resulting in cell death. These dual inhibitors, when orally co-administered with TPT, enhanced TPT bioavailability with slightly reduced total oral clearance (Clt/F) in rats. In xenograft mice, they strengthened oral TPT-induced tumor reduction with no alterations in body weight. Moreover, we investigated the effects of an oral drug formulation (Cremophor® EL, Tween® 80, and polyethylene glycol 400) on the transporters function. The excipients increased TPT accumulation in P-gp- or BCRP-overexpressing cells. Oral TPT bioavailability was higher with the formulation than with a control, as shown by the increases in the maximum plasma concentration (Cmax) and the area under the plasma concentration–time curve from zero to infinity (AUCINF) (p 〈 0.01). Therefore, oral TPT bioavailability was enhanced by P-gp/BCRP dual inhibition, which resulted in a formulation-mediated increase in absorption and decrease in elimination, and a dual inhibitor-mediated decrease in elimination. These results suggest that the combination of dual inhibition by a natural derivative and the drug formulation can be a useful clinical approach.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics13040559
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model
    MDPI AG ; 2022
    In:  Life Vol. 12, No. 3 ( 2022-03-14), p. 421-
    Details
    In: Life, MDPI AG, Vol. 12, No. 3 ( 2022-03-14), p. 421-
    Abstract: Steroids are currently being used in sepsis, particularly in septic shock. However, clinical trials to date have shown contradictory results. This could be attributed to the different patient endotypes and steroid doses, which have also contributed to the inconclusive results. We investigated the effects of glucocorticoid therapy on sepsis in a polymicrobial sepsis model in a variety of settings, such as steroid dose, severity, and sepsis phase. We used a rat model of fecal slurry polymicrobial sepsis. First, we investigated the optimum dose of steroids in a sepsis model. We administered different doses of dexamethasone after sepsis induction (0.1DEX; 0.1 mg/kg, 0.2DEX; 0.2 mg/kg, 5DEX; 5 mg/kg). Second, we used two different severities of the fecal slurry polymicrobial sepsis rat model to examine the effects of the steroids. A moderate or severe model was defined as a survival rate of approximately 70% and 30%, respectively. Third, we administered steroids in an early (1 h after sepsis induction) or late phase (25 h after sepsis). In all the experiments, we investigated the survival rates. In the determined optimal model and settings, we measured serum lactate, alanine transferase (ALT), creatinine, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, and arterial blood gas. We evaluated the bacterial burden in the blood and spleen. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was also investigated to determine the level of immune suppression 24 h after sepsis by measuring TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. Early treatment of 0.2 mg/kg dexamethasone in a severe sepsis model showed the best beneficial effects. In moderate- or late-phase sepsis, there was no survival gain with steroid treatment. DEX0.2 group showed less acute kidney injury manifested by serum creatinine and blood urea nitrogen. DEX decreased the levels of cytokines, including IL-6, IL-10, and TNF-α. Colony-forming units were significantly decreased in the blood when administered with dexamethasone. Endotoxin tolerance was not significantly different between the DEX0.2 and control groups. In conclusion, early treatment of 0.2 mg/kg dexamethasone improved the outcomes of rats in a severe sepsis model.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life12030421
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662250-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Characteristics, Location, and Clinical Outcomes of Gastrointestinal Bleeding in Patients Taking New Oral Anticoagulants Compared to Vitamin K Antagonists
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 12 ( 2021-06-18), p. 2693-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 12 ( 2021-06-18), p. 2693-
    Abstract: New oral anticoagulants (NOACs) are commonly used in clinical practice as alternatives to vitamin K antagonists (VKA). However, the etiology, clinical course, and risk of gastrointestinal (GI) bleeding remain unclear. We aimed to evaluate the clinical characteristics and location of acute GI bleeding associated with NOACs and its severity and outcomes compared to VKA. This retrospective multicenter study included 381 subjects on anticoagulants who underwent appropriate diagnostic examination due to GI bleeding. Regarding the characteristics of acute GI bleeding, the proportion of vascular lesions was significantly lower in the NOACs group than that in the VKA group. Small bowel bleeding occurred less commonly in the NOACs group, but the difference did not reach statistical significance. Regarding severity and clinical outcomes, patients on NOACs received significantly smaller volumes of transfused blood products and had shorter ICU stays than those on VKA. Moreover, the need for surgery and the risk of rebleeding in the NOACs group were significantly lower than those in the VKA group. Patients on NOACs have better clinical outcomes in terms of severity of acute GI bleeding or rebleeding than patients on VKA. Patients on NOACs demonstrate different characteristics and location of acute GI bleeding than those on VKA.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10122693
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...