Recent studies indicate the presence of systemic inflammation in psoriatic patients, and this inflammatory status is significantly associated with a range of comorbidities. The aim of this study was ...to evaluate the clinical significance of novel inflammatory biomarkers, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and mean platelet volume (MPV) in Japanese patients with plaque‐type psoriasis (PsV) and psoriatic arthritis (PsA). One hundred and eighty‐six patients with PsV and 50 patients with PsA treated with biologics, including infliximab, adalimumab and ustekinumab, were retrospectively analyzed before and after treatment. At baseline, NLR and PLR, as well as C‐reactive protein (CRP), were significantly higher in PsA patients than those in PsV patients, and a significant correlation was found between NLR and PLR. In PsV patients, the NLR‐high and PLR‐high subgroups exhibited significantly higher Psoriasis Area and Severity Index scores compared with the NLR‐low and PLR‐low subgroups, respectively, and the NLR‐high subgroup also showed higher CRP levels. MPV value was negatively associated with the presence of arthritis, but its association with inflammation was less clear than that of NLR or PLR. After treatment of the patients with biologics for up to 12 months, NLR and PLR decreased promptly in parallel with a decrease of CRP, irrespective of the type of biologics used. Altogether, these results indicate that both NLR and PLR may be useful markers to evaluate systemic inflammation in psoriatic patients. They may serve as simple, convenient and cost‐effective biomarkers to monitor the disease course after systemic therapy.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Asthma is a chronic inflammatory disease of airways, but an ideal biomarker that accurately reflects ongoing airway inflammation has not yet been established. The aim of this study was to examine the ...potential of sputum leucine-rich alpha-2 glycoprotein (LRG) as a new biomarker for airway inflammation in asthma.
We obtained induced sputum samples from patients with asthma (N = 64) and healthy volunteers (N = 22) and measured LRG concentration by sandwich enzyme-linked immunosorbent assay (ELISA). Ovalbumin (OVA)-induced asthma model mice were used to investigate the mechanism of LRG production during airway inflammation. The LRG concentrations in the bronchoalveolar lavage fluid (BALF) obtained from mice were determined by ELISA and mouse lung sections were stained with anti-LRG antibody and periodic acid-Schiff (PAS) reagent.
Sputum LRG concentrations were significantly higher in patients with asthma than in healthy volunteers (p = 0.00686). Consistent with patients' data, BALF LRG levels in asthma model mice were significantly higher than in control mice (p = 0.00013). Immunohistochemistry of lung sections from asthma model mice revealed that LRG was intensely expressed in a subpopulation of bronchial epithelial cells, which corresponded with PAS-positive mucus producing cells.
These findings suggest that sputum LRG is a promising biomarker of local inflammation in asthma.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Leucine-rich alpha 2 glycoprotein (LRG) has been identified as a serum protein elevated in patients with active rheumatoid arthritis (RA). Although the function of LRG is ill-defined, LRG binds with ...transforming growth factor (TGF)-β and enhances Smad2 phosphorylation. Considering that the imbalance between T helper 17 (Th17) cells and regulatory T cells (Treg) plays important roles in the pathogenesis of RA, LRG may affect arthritic pathology by enhancing the TGF-β-Smad2 pathway that is pivotal for both Treg and Th17 differentiation. The purpose of this study was to explore the contribution of LRG to the pathogenesis of arthritis, with a focus on the role of LRG in T cell differentiation.
The differentiation of CD4 T cells and the development of collagen-induced arthritis (CIA) were examined in wild-type mice and LRG knockout (KO) mice. To examine the influence of LRG on T cell differentiation, naïve CD4 T cells were isolated from LRG KO mice and cultured under Treg- or Th17-polarization condition in the absence or presence of recombinant LRG.
In the CIA model, LRG deficiency led to ameliorated arthritis and reduced Th17 differentiation with no influence on Treg differentiation. By addition of recombinant LRG, the expression of IL-6 receptor (IL-6R) was enhanced through TGF-β-Smad2 signaling. In LRG KO mice, the IL-6R expression and IL-6-STAT3 signaling was attenuated in naïve CD4 T cells, compared to wild-type mice.
Our findings suggest that LRG upregulates IL-6R expression in naïve CD4 T cells by the enhancement of TGF-β-smad2 pathway and promote Th17 differentiation and arthritis development.
Introduction: Brushing older adults or intubated patients who are unable to rinse can transmit bacteria from dental plaque into the oral cavity and increase the risk of aspiration pneumonia. ...Therefore, this study examined brushing methods to prevent the spread of bacteria in the oral cavity. Methods: Three types of brushing methods were performed on five volunteers by dental hygienists (water group: brushing with toothbrush bristles soaked in water; gel group: brushing with a moisturizing gel placed on the toothbrush; PV-I group: brushing with toothbrush bristles dipped in povidone-iodine). Neither group spat out the saliva or gargled during brushing but brushed while wiping the water/gel/PV-I solution with a sponge brush. The same five volunteers served as subjects for the three methods. Saliva was collected before and after brushing, and the number of colonies was determined using bacterial culture. Results: The water group demonstrated a significantly increased number of bacteria in the saliva owing to the spread of bacteria from the dental plaque. The gel group prevented the spread of the bacteria. The PV-I group showed a significant decrease in the number of bacteria in the saliva after brushing.Conclusions: Brushing with toothbrush bristles dipped in a povidone-iodine solution is recommended for intubated or older adult patients who cannot gargle.
Oral care is important in preventing aspiration pneumonia in older adults. However, it is not clear what kind of oral care can reduce the number of bacteria in saliva. The purposes of this study are ...to clarify whether there is a relationship between plaque amounts and salivary bacterial counts, and how bacteria dispersed into the oral cavity by brushing can be reduced.
First, saliva samples were collected from 10 healthy adult volunteers after 30 h of unbrushing and after thorough brushing, and the total bacterial count was determined by real-time PCR. Next, 40 older adults attending an outpatient dental clinic were randomly assigned into two groups: a wiping group (20 patients) and a mouthwashing group (20 patients). Saliva was collected before and after brushing, and after wiping in the wiping group and after mouthwashing in the mouthwashing group, and the total bacterial count was quantified by real-time PCR.
In a study of volunteers, there was no association between plaque amounts and salivary bacterial counts. In a study of older adult patients, salivary bacterial counts were significantly higher in patients with higher oral hygiene index and fewer remaining teeth. Brushing increased salivary bacterial counts. Wiping did not significantly reduce the number of bacteria, while mouthwash returned the increased number of bacteria after brushing to the pre-brushing level.
There is no direct relationship between the amount of plaque and the number of bacteria in saliva. Brushing disperses bacteria into the oral cavity, resulting in a marked increase in the number of bacteria in saliva. Wiping does not collect the dispersed bacteria, and it seems essential to rinse the mouth after brushing.
UMIN000045854.
Background Melanoma is a malignant tumor characterized by high proliferation and aggressive metastasis. To address the molecular mechanisms of the proto-oncogene, Rous sarcoma oncogene (Src), which ...is highly activated and promotes cell proliferation, migration, adhesion, and metastasis in melanoma. Plectin, a cytoskeletal protein, has recently been identified as a Src-binding protein that regulates Src activity in osteoclasts. Plectin is a candidate biomarker of certain tumors because of its high expression and the target of anti-tumor reagents such as ruthenium pyridinecarbothioamide. The molecular mechanisms by which plectin affects melanoma is still unclear. In this study, we examined the role of plectin in melanoma tumor formation. Methods We used CRISPR/Cas9 gene editing to knock-out plectin in B16 mouse melanoma cells. Protein levels of plectin and Src activity were examined by western blotting analysis. In vivo tumor formation was assessed by subcutaneous injection of B16 cells into nude mice and histological analysis performed after 2 weeks by Hematoxylin-Eosin (H&E) staining. Cell proliferation was evaluated by direct cell count, cell counting kit-8 assays, cyclin D1 mRNA expression and Ki-67 immunostaining. Cell aggregation and adhesion were examined by spheroid formation, dispase-based dissociation assay and cell adhesion assays. Results In in vivo tumor formation assays, depletion of plectin resulted in low-density tumors with large intercellular spaces. In vitro experiments revealed that plectin-deficient B16 cells exhibit reduced cell proliferation and reduced cell-to-cell adhesion. Since Src activity is reduced in plectin-deficient melanomas, we examined the relationship between plectin and Src signaling. Src overexpression in plectin knockout B16 cells rescued cell proliferation and improved cell-to-cell adhesion and cell to extracellular matrix adhesion. Conclusion These results suggest that plectin plays critical roles in tumor formation by promoting cell proliferation and cell-to-cell adhesion through Src signaling activity in melanoma cells. Keywords: Melanoma, Src, Plectin, Tumor genesis, Cell adhesion
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. ...Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First‐line therapies were infliximab (IFX, n = 26), adalimumab (ADA, n = 18) and ustekinumab (UST, n = 7), and second‐line therapies were IFX (n = 5), ADA (n = 21) and UST (n = 25). Reasons for switching were inefficacy (n = 38), adverse events (n = 11) and others (n = 2). The details were primary failure (n = 15), secondary failure (n = 23) and infusion reactions (n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index (PASI) score at week 16 was 4.3 for first‐line therapies and 2.9 for second‐line therapies (P < 0.05). Switching to a second biologic therapy to address the first's inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Although end-of-life patients have a variety of oral-related symptoms, the involvement of dentists and dental hygienists in the palliative care teams is limited. This study ...investigates the current state of palliative care education in universities that train dentists and dental hygienists and the need for dentistry in the clinical setting of palliative medicine in Japan.
Methods
First, we investigated the involvement of dentistry in hospitals with palliative care units from a website. The number of reports on palliative care presented by dental hygienists at academic conferences around 2016, when the public medical insurance system in Japan covered oral care for patients with terminal illnesses, were examined. We also surveyed the syllabuses of the university that trained nurses, dentists, and dental hygienists to determine their education regarding palliative care.
Results
Of the 376 hospitals with palliative care units, 176 (46.8%) had dentistry in the hospital. Additionally, 321 hospitals (85.4%), which included those without dentistry, responded that they provided oral care by dentists and dental hygienists in the palliative care unit. There were only two presentations on palliative care in the annual meetings of the two major academic societies by dental hygienists between 2012 and 2016. However, this number increased rapidly to 47 between 2017 and 2020. The syllabus surveys showed that, compared to nursing universities, universities that trained dentists or dental hygienists had lesser education in palliative care. Furthermore, education in the universities that trained dental hygienists was mostly related to the oral care of patients with terminal illnesses, while the physical and mental conditions of end-of-life patients were not well educated.
Conclusion
Considering that society requires the involvement of dental hygienists in the field of palliative care, it is necessary to enhance basic and clinical education of palliative care in universities that train dentists and dental hygienists to provide good oral care to patients with terminal illnesses and contribute to improving their quality of life.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ustekinumab (UST) is a treatment option for psoriatic arthritis (PsA), but recent observations indicate that some psoriatic patients may experience new onset of PsA or worsening of pre‐existent PsA. ...We retrospectively analyzed all cases of psoriasis vulgaris (PsV) and PsA treated with UST in our facility between 2011 and 2015. PsA developed in eight out of 179 PsV patients, mostly later than 8 months after initiation of UST. It was generally not severe, and none had received tumor necrosis factor (TNF)‐α inhibitors previously, indicating that the possibility of unmasking pre‐existing subclinical arthritis is minimal. The eruptions were well controlled at the time of the onset of arthritis in most cases. Interestingly, those who developed arthritis showed a significantly lower body mass index. Regarding pre‐existing PsA, nine PsA patients received UST, and at least partial improvement of PsA could be achieved in two out of three bio‐naive and three out of six bio‐switched patients from TNF‐α inhibitors. PsA was largely more refractory to UST than the eruptions. Altogether, our present study is in agreement with the notion that UST may be less efficient than TNF‐α inhibitors for PsA. While UST cannot fully prevent new development of PsA, it is unlikely that UST increases the risk of new onset of PsA as a paradoxical adverse reaction.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
PDF
