Background
Club cell 16‐kDa secretory protein (CC16) is a pneumoprotein and functions as an anti‐inflammatory or antioxidant protein. However, altered levels of serum CC16 as well as their effect on ...airways inflammation have not been fully evaluated.
Methods
We recruited 63 adult asthmatics on maintenance medications and 61 healthy controls (HCs). The asthmatic subjects were divided into two groups according to the result of bronchodilator responsiveness (BDR) test: the present BDR (n = 17) and absent BDR (n = 46) groups. Serum CC16 levels were measured by ELISA. As an in vitro study, the effect of Dermatophagoides pteronyssinus antigen 1 (Der p1) on the production of CC16 in airways epithelial cells (AECs) according to a time‐dependent manner was assessed; the effects of CC16 protein on oxidative stress system, airways inflammation and remodelling were tested.
Results
Serum CC16 levels showed significantly higher in the asthmatics than in the HCs (p < .001) with a positive correlation with FEV1% (r = .352, p = .005). The present BDR group had significantly lower levels of serum CC16, FEV1% and MMEF%, but showed higher level of FeNO than the absent BDR group. Serum CC16 levels (below 496.0 ng/mL) could discriminate the present BDR group from the absent BDR group (area under the curve = 0.74, p = .004). In vitro testing demonstrated that Der p1 exposure significantly induced CC16 release from AECs for 1 h, which was progressively decreased after 6 h and followed by MMP‐9 and TIMP‐1 production. These findings were associated with oxidant/antioxidant disequilibrium and restored by CC16 treatment (but not dexamethasone).
Conclusion
Decreased CC16 production contributes to persistent airways inflammation and lung function decline. CC16 may be a potential biomarker for asthmatics with BDR.
Asthmatics in the present BDR group had greater levels of serum MMP‐9/MPO and FeNO, and lower levels of serum CC16, MMEF% and FEV1% than those in the absent BDR group. FEV1% positively correlated with serum CC16 levels. CC16 down‐regulation in HDM‐stimulated AECs was associated with an imbalance of oxidant (NF‐κB and GSSG)/antioxidant (Nrf‐2, HO‐1 and GSH) systems and proinflammatory cytokine outputs (IL‐8, MMP‐9 and TIMP‐1).
Axons in the adult mammalian central nervous system fail to regenerate after injury. By contrast, spontaneous axon regeneration occurs in the peripheral nervous system (PNS) due to a supportive PNS ...environment and an increase in the intrinsic growth potential induced by injury via cooperative activation of multifaceted biological pathways. This study compared axon regeneration and injury responses in C57BL/6 male and female mice after sciatic nerve crush (SNC) injury. The extent of axon regeneration in vivo was indistinguishable in male and female mice when observed at 3 days after SNC injury, and primary dorsal root ganglion (DRG) neurons from injured, male and female mice extended axons to a similar length. Moreover, the induction of selected regeneration‐associated genes (RAGs), such as Atf3, Sprr1a, Gap43, Sox11, Jun, Gadd45a, and Smad1 were comparable in male and female DRGs when assessed by quantitative real‐time reverse transcription polymerase chain reaction. Furthermore, the RNA‐seq analysis of male and female DRGs revealed that differentially expressed genes (DEGs) in SNC groups compared to sham‐operated groups included many common genes associated with neurite outgrowth. However, we also found that a large number of genes in the DEGs were sex dependent, implicating the involvement of distinct gene regulatory network in the two sexes following peripheral nerve injury. In conclusion, we found that male and female mice mounted a comparable axon regeneration response and many RAGs were commonly induced in response to SNC. However, given that many DEGs were sex‐dependently expressed, future studies are needed to investigate whether they contribute to peripheral axon regeneration, and if so, to what extent.
In the mammalian peripheral nervous system, axon regeneration occurs spontaneously after injury. This study examined if axon regeneration after sciatic nerve crush injury was sex dependent and found that the extent of axon regeneration was indistinguishable in male and female mice. Transcriptome analysis revealed that many genes associated with neurite outgrowth were commonly induced in the two sexes, despite that a majority of genes were sex‐dependently induced by injury. Therefore, although male and female mice exhibit similar axon regeneration, the mechanisms involved might not be identical.
An novel concept for integrating visible light produced by LEDs with indoor positioning using multiple optical receivers is presented in this study. We propose an algorithm using the received signal ...strength indication (RSSI), which changes by on transmission distance and angle. In order to estimate the position, the transmitters location code was received using multiple optical receivers. The validity of the proposed scheme was demonstrated by determining the local position using distances between the transmitter and receivers, and the relative position between receivers.
As the COVID-19 pandemic continues, wearing a mask has become a daily routine in Korea over the last two years. This study aims to investigate the mask-wearing perception of preschoolers (ages 4-6). ...The questionnaire comprised 17 yes-no closed-ended questions and two open-ended questions, and interviews of the children were conducted from January to February 2022, 15 months after mandatory mask wearing. Results showed that children were aware of the need to wear a mask to protect themselves and others from the coronavirus, and they perceived it as necessary and a good thing. Most children responded that they did not feel uncomfortable wearing a mask at preschool. This perception was thought to be influenced by the caregivers' perceptions of the mask in Korea. The way in which 4-5-year-olds perceived the mask differed from the way 6-year-olds did. Children aged between four and five seemed to perceive the mask as a physical self, while children aged six did not. As children who have experienced COVID-19 are growing up, attention is being focused on how the experience of wearing a mask affects their early childhood development.
C57BL/6 mice are known to be resistant to the development of collagen-induced arthritis (CIA). However, they show a severe arthritic phenotype when the Ifng gene is deleted. Although it has been ...proposed that IFN-γ suppresses inflammation in CIA via suppressing Th17 which is involved in the pathogenesis of CIA, the exact molecular mechanism of the Th17 regulation by IFN-γ is poorly understood. This study was conducted to 1) clarify that arthritogenic condition of IFN-γ knockout (KO) mice is dependent on the disinhibition of Th17 and 2) demonstrate that IFN-γ-induced indoleamine-2,3-dioxgenase (IDO) is engaged in the regulation of Th17. The results showed that the IFN-γ KO mice displayed increased levels of IL-17 producing T cells and the exacerbation of arthritis. Also, production of IL-17 by the splenocytes of the IFN-γ KO mice was increased when cultured with type II collagen. When Il17 was deleted from the IFN-γ KO mice, only mild arthritis developed without any progression of the arthritis score. The proportion of CD44(high)CD62L(low) memory-like T cells were elevated in the spleen, draining lymph node and mesenteric lymph node of IFN-γ KO CIA mice. Meanwhile, CD44(low)CD62L(high) naïve T cells were increased in IFN-γ and IL-17 double KO CIA mice. When Th17 polarized CD4+ T cells of IFN-γ KO mice were co-cultured with their own antigen presenting cells (APCs), a greater increase in IL-17 production was observed than in co-culture of the cells from wild type mice. In contrast, when APCs from IFN-γ KO mice were pretreated with IFN-γ, there was a significant reduction in IL-17 in the co-culture system. Of note, pretreatment of 1-methyl-DL- tryptophan, a specific inhibitor of IDO, abolished the inhibitory effects of IFN-γ. Given that IFN-γ is a potent inducer of IDO in APCs, these results suggest that IDO is involved in the regulation of IL-17 by IFN-γ.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Anti‐heat shock protein (HSP) autoantibodies are detected in autoimmune diseases. We sought to ascertain whether anti‐HSP10 IgG is present in patients with CSU and to elucidate the role of ...HSP10 in CSU pathogenesis.
Method
Using a human proteome microarray, six potential autoantibodies had higher expression in 10 CSU samples compared with 10 normal controls (NCs). Among them, HSP10 IgG autoantibody was quantified by immune dot‐blot assay in sera from 86 CSU patients and 44 NCs. The serum levels of HSP10 and microRNA‐101‐5p were measured in CSU patients and NCs. The effects of HSP10 and miR‐101‐5p on mast cell degranulation in response to IgE, compound 48/80, and platelet‐activating factor (PAF) were investigated.
Results
CSU patients had higher IgG positivity to HSP10 (40.7% vs. 11.4%, p = .001), lower serum HSP10 levels (5.8 ± 3.6 vs. 12.2 ± 6.6 pg/mL, p < .001) than in NCs, and their urticaria severity was associated with anti‐HSP10 IgG positivity, while HSP10 levels were related to urticaria control status. MiR‐101‐5p was increased in CSU patients. PAF enhanced IL4 production in PBMCs from CSU patients. IL‐4 upregulated miR‐101‐5p and reduced HSP10 expression in keratinocytes. Transfection of miR‐101‐5p reduced HSP10 expression in keratinocytes. MiR‐101‐5p promoted PAF‐induced mast cell degranulation, while HSP10 specifically prevented it.
Conclusion
A new autoantibody, anti‐HSP10 IgG was detected in CSU patients, which showed a significant correlation with UAS7 scores. A decreased serum HSP10 level was associated with upregulation of miR‐101‐5p due to increased IL‐4 and PAF in CSU patients. Modulation of miR‐101‐5p and HSP10 may be a novel therapeutic approach for CSU.
In patients with CSU, the positivity of anti‐HSP10 IgG was increased and associated with urticaria severity. Additionally, HSP10 levels were decreased and correlated with UCT scores after 6‐month treatment in CSU patients. Serum IL‐4 levels were elevated in CSU patients, and treatment with IL‐4 in HUVECs and HaCaT cells resulted in a reduction in HSP10, which was caused by the upregulation of miR‐101‐5p in these cells. Increased IL‐4 production was observed from PBMCs of CSU patients and HUVECs upon PAF stimulation, and HSP10 was found to prevent PAF‐induced mast cell degranulation.Abbreviations: AH, platelet‐activating factor‐acetylhydrolase; CSU, chronic spontaneous urticaria; HaCaT, human keratinocyte cell line; hiPSC‐MC, human induced pluripotent stem cell‐derived mast cells; HSP10, heat shock protein 10; HUVEC, human umbilical vein endothelial cell; miR, microRNA; NC, healthy normal control; PAF, platelet‐activating factor; PAF‐UCT, urticaria control test; PBMC, peripheral blood mononuclear cells; UAS7, urticaria activity score over 7 days.
Tonsil-derived mesenchymal stem cells (TMSC) have characteristics of MSC and have many advantages. In our previous studies, intraperitoneal (IP) injection of TMSC in acute and chronic colitis mouse ...models improved the disease activity index, colon length, and the expression levels of proinflammatory cytokines. However, TMSC were not observed to migrate to the inflammation site in the intestine. The aim of this study was to verify the therapeutic effect of conditioned medium (CM) released by TMSC (TMSC-CM) in a mouse model of dextran sulfate sodium (DSS)-induced chronic colitis. TMSC-CM was used after seeding 5×105 cells onto a 100 mm dish and culturing for 5-7 days. TMSC-CM was concentrated (TMSC-CM-conc) by three times using a 100 kDa cut-off centrifugal filter. Seven-week-old C57BL/6 mice were randomly assigned to the following 5 groups: 1) normal, 2) colitis, 3) TMSC, 4) TMSC-CM, and 5) TMSC-CM-conc. Chronic colitis was induced by continuous oral administration of 1.5% dextran sulfate sodium (DSS) for 5 days, followed by 5 additional days of tap water feeding. This cycle was repeated two more times (total 30 days). Phosphate buffered saline (in the colitis group), TMSC, TMSC-CM, and TMSC-CM-conc were injected via IP route 4, 4, 12, and 4 times, respectively. Reduction of disease activity index, weight gain, recovery of colon length, and decreased in the expression level of the proinflammatory cytokines, interleukin (IL)-1β, IL-6, and IL-17 were observed at day 30 in the treatment groups, compared to control. However, histological colitis scoring and the expression level of tumor necrosis factor α and IL-10 did not differ significantly between each group. TMSC-CM showed an equivalent effect to TMSC related to the improvement of inflammation in the chronic colitis mouse model. The data obtained support the use of TMSC-CM to treat inflammatory bowel disease without any cell transplantation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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