Medium optimization and dust suppression performance analysis of microbial-based dust suppressant compound by response surface curve method.

At present, microbial dust suppressants based on microbial communities lack necessary systematic analysis of factors affecting dust suppression performance. Therefore, in this study, the response surface curve method was used to optimize the culture conditions for enrichment of urease-producing microorganisms from activated sludge. The results indicated that when urea = 9.67 g L-1, NH4Cl = 5.21 g L-1, and pH = 9.57, the maximum urease activity of urease-producing microbial community (UPMC) was 8.22 mM min-1. The UPMC under optimized culture conditions reached a mineralization rate of 98.8% on the 1st day of mineralization. Ureolysis is one of the biological mechanisms that trigger microbial mineralization with the consequent effect of dust suppression. The analysis of microbial community structure indicated that the urease-producing bacteria Sporosarcina sp. had the highest abundance at the genus level in the microbial-based dust suppressant compound. Jeotgalicoccus sp. plays an important role in improving and maintaining the stability of urease. In addition, the optimal UPMC had low pathogenicity, which is extremely attractive for the safe application of microbial dust suppressants.

A Common Functional Variant at the Enhancer of the Rheumatoid Arthritis Risk Gene ORMDL3 Regulates its Expression Through Allele-Specific JunD Binding.

Genome-wide association studies (GWASs) have identified over 100 loci associated with rheumatoid arthritis (RA); however, the functionally affected genes and the underlying molecular mechanisms contributing to these associations are often unknown. In this study, we conducted an integrative genomic analysis incorporating multiple "omics" data and identified a functional regulatory DNA variant, rs56199421, and a plausible mechanism by which it regulates the expression of a putative RA risk gene, ORMDL Sphingolipid Biosynthesis Regulator 3 (ORMDL3). The T allele of rs56199421, located in the enhancer region of ORMDL3, exhibited stronger direct binding ability than the other C allele of rs56199421 did in vitro with the transcription factor JunD and demonstrated higher transcriptional activity. Moreover, the T allele of rs56199421 is associated with elevated RA risk, and ORMDL3 expression is increased in RA patients. Thus, these findings suggest that the T allele of rs56199421 enhances JunD transcription factor binding, increases enhancer activity, and elevates the expression of the RA risk gene ORMDL3. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00107-z.

Effect of surfactant on urease-producing flora from waste activated sludge using microbially induced calcite precipitation technology to suppress coal dust.

The wettability of microbially induced calcite precipitation (MICP) is a challenge in dust suppression. Herein, the tolerance of urease-producing flora to surfactants was investigated. The optimal tolerance concentrations of the urease-producing flora to sodium dodecylbenzene sulfonate (SDBS, anionic surfactant), alkyl polyglycoside (APG, non-ionic surfactant), and cocamidopropyl betaine (CAB, zwitterionic surfactant), and were 0.2%, 0.1%, and 0.05%. The cetyltrimethylammonium bromide (CTAB, cationic surfactant) inhibited urease production by urease-producing flora. The mineralization products of SDBS, APG, and CAB treatments were all transformed into calcite. The wind resistance test showed that the mass loss of all samples is less than 0.1%. The rain resistance and hardness tests showed that 0.2% SBDS had the best effect, followed by 0.1% APG and 0.05% CAB, and finally, No surfactants. Microbiome analysis showed that the abundance of Sporosarcina and Unclassified_bacillaceae reduced, and the intense competition between Paenalcaligenes and Sporosarcina are essential reasons for reducing urease activity. SDBS and APG could reduce the pathogenic risk of microbial dust suppressants. This study will facilitate the practical application of microbial dust suppressants.

Recent Insights Into the Role of Macrophages in Acute Gout.

Gout is a common type of inflammatory arthritis characterized by the presence of monosodium urate crystals (MSU) in the joints. Macrophages are believed to be involved in gout flares. It has long been recognized that resident macrophage and monocyte derived macrophages are distinct subsets and there have been attempts to investigate their roles in acute gout, respectively. Previous studies revealed that resident macrophages initiate and drive the inflammation, while monocyte derived macrophages differentiated into M1-like macrophages in response to MSU crystals. With the advancement of technologies, subpopulations of synovial resident macrophages have been defined with the characteristics more accurately described. Resident macrophages in the synovial lining layer showed an anti-inflammatory effect in rheumatoid arthritis, but specific Trpv4 depletion of them reduced MSU crystals induced murine arthritis. CD14+ monocytes in the synovial fluid from patients with gout exhibit phenotypes of anti-inflammatory as well as pro-inflammatory characteristics. Here, we review the main aspects of macrophages in the initiation and resolution of acute gout and try to clarify the specific role of each subpopulation. Building a reliable diagram of the effect of monocytes and macrophages during MSU crystals induced arthritis will bring us closer to targeting macrophages for improving the management of gout.

Natural Adrenocorticotropic Hormone (ACTH) Relieves Acute Inflammation in Gout Patients by Changing the Function of Macrophages.

Gout is a common arthritis caused by deposition of monosodium urate crystals. Macrophage is crucial in the process of monosodium urate (MSU)-induced inflammation. Although it has been reported that adrenocorticotropic hormone (ACTH) in nature can be used to cure urarthritis, the mechanism concerning macrophage is still not clear. However, gout patients manifest other complications, such as hypertension, diabetes, chronic kidney disease, and hormone intolerance, which limit efficacy of some of these first-line drugs. Therefore, this study aims to explore how natural ACTH can alleviate urarthritis through functional changes in macrophage. We analyzed the variations in VAS pain scores of five patients, knowing the time of action and detecting the level of cortisol and ACTH in patients 24 hours after the application of ACTH. The effect of natural ACTH on joint inflammation and the level of cortisol in blood in the mouse model was evaluated by studies in vivo. In vitro studies, we evaluated the effect of natural ACTH on macrophages and revealed different functions of ACTH and dexamethasone on macrophages in the transcriptional level. In patients with acute gout, natural ACTH can quickly alleviate pain and does not affect the level of cortisol and ACTH. Natural ACTH is able to ease the swelling and inflammatory cell infiltration caused by arthritis, without changing the level of cortisol. Besides, natural ACTH in vitro can alleviate acute gouty inflammation by regulating phagocytosis and polarization of macrophage, which also exerts different effects on the transcription of some related genes. Natural ACTH is able to alleviate acute gouty inflammation by regulating macrophage, and this effect differs from that of dexamethasone at the transcriptional level.

Distinct macrophage polarization in acute and chronic gout.

Macrophage polarization mediates the development of inflammatory diseases. However, the polarization status at various stages of gout is not fully understood. Our study aimed to define the evolution of macrophage polarization in acute and chronic gout. Normal human synovium and synovium with tophi were collected for immunofluorescence (IF). Rat gouty joints were collected for joint thickness assessment and pathological evaluation. Tissue mRNA expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) were evaluated. Mouse peritoneal macrophages and THP-1 derived macrophages were stimulated by monosodium urate (MSU) crystals and were collected for detection of interleukin (IL) -1ß and IL-37 levels and iNOS/Arg-1 ratio. Arg-1 and IL-37 were highly expressed in normal synovium and synovium with tophi. In rat gouty joints, the inflammatory cell counts and ankle thickness began to increase at 2 h, peaked at 24 h, and was decreased spontaneously. An increase in macrophages preceded the neutrophils infiltration. Infiltration of M1 was positively related with the severity of arthritis. M2 appeared in an early stage (at 2 h) of inflammation. The number of M1 macrophages was comparable to that of M2 from 2 to 12 h and exceeded M2 number at 18 h and 24 h. The ratios of M2/M1 reversed at 48 h and remained reversed until 120 h. In mice gouty joints, iNOS/Arg-1 mRNA ratio was significantly higher than the that in control group at 8 h. The proportion of neutrophils and M1-macrophages reached peak at 4 h in mice model with peritoneal gout. Concentration of IL-1ß and ratio of iNOS/Arg-1 were increased at 6 h, peaked at 48 h, and were then decreased at 72 h in vitro, while the concentration of IL-37 peaked at 2 h and then decreased. In summary, altered macrophage polarization was observed in various stages of gouty inflammation. Macrophages in acute gout were polarized into M1 at early stage and into M2 at later stage while the macrophages in chronic gout mainly were only polarized towards M2. The number of M1 rose with the progression of inflammation. Early increase of M2 was observed, which might be generated directly from M0.

IL-37 blocks gouty inflammation by shaping macrophages into a non-inflammatory phagocytic phenotype.

OBJECTIVE: Interleukin (IL)-37 is a natural suppressor of inflammation. Macrophages play an important role in acute gout flare by dominating the inflammation and spontaneous relief. We have reported that IL-37 could limit runaway inflammation in gout. Here we focus on whether IL-37 inhibits gouty inflammation by altering macrophage functions, and how it does so. METHODS: Macrophage functions were evaluated in terms of phagocytosis, pyroptosis, polarization and metabolism. Phagocytosis and polarization of macrophages were detected by side scattering and double-labelling induced nitrogen monoxide synthase (iNOS)/arginase-1 (Arg-1) using flow cytometry, respectively. Transcription of pyroptosis-related molecules was detected by qPCR. Metabolomics was performed by liquid chromatograph mass spectrometer. Human IL-37 knock-in mice and a model with point mutation (S9A) at mouse Gsk3b locus were created by CRISPR/Cas-mediated genome engineering. MSU was injected into the paws and peritoneal cavity to model acute gout. Vernier calliper was used to measure the thickness of the paws. The mice paws and human synovium tissues or tophi were collected for pathological staining. Peritoneal fluid of mice was used to enrich macrophages to detect polarization. RESULTS: IL-37 promoted non-inflammatory phagocytic activity of macrophages by enhancing phagocytosis of MSU, reducing transcription of pyroptosis-related proteins and release of inflammatory cytokines, protecting mitochondrial function, and mediating metabolic reprogramming in MSU-treated THP-1 cells. These multifaceted roles of IL-37 were partly depended on the mediation of glycogen synthase kinase-3ß (GSK-3ß). CONCLUSIONS: Our study revealed that IL-37 could shape macrophages into a 'silent' non-inflammatory phagocytic fashion. IL-37 may become a potentially valuable treatment option for patients of chronic gout, especially for those with tophi.

Bone mineral density, bone metabolism-related factors, and microRNA-218 are correlated with disease activities in Chinese ankylosing spondylitis patients.

OBJECTIVE: To investigate bone mineral density (BMD), bone metabolism-related factors, and microRNA-218 in Chinese ankylosing spondylitis (AS) patients and to identify their correlation with disease activities and the treatment with TNF-α inhibitors. METHODS: A total of 89 AS patients were enrolled in the study. Patients' information and laboratory examination results were collected. BMD of the anteroposterior lumbar spine (L2-L4), left femoral neck, and whole body were measured and T-scores were calculated. MicroRNA-218 was extracted from PBMCs of AS patients and detected by RT-PCR. Bone metabolism-related factors were detected using protein chips and flow cytometer. RESULTS: Out of 86 patients undergoing whole-body BMD measurement, 14 had osteopenia and 72 had normal BMD without osteoporosis or high BMD. Compared with short- (disease duration ≤3 years) and long-term groups (disease duration ≥10 years), medium-term group (disease duration ranges from 3 to 10 years) showed lowest BMD. Patients with onset age ≤20 years old had significantly lower BMD than the other groups (p < 0.05). The BMD of femoral neck had negative correlation with CRP (p < 0.05) and no correlation with BASDAI or ESR. Both whole-body BMD and femoral neck BMD were negatively correlated with BASMI (p < 0.05). Dickkopf-1 (DKK-1), platelet-derived growth factor-BB (PDGF-BB), and receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) were significantly increased, while Osteopontin (OPN) was significantly decreased in AS patients. Expression of microRNA-218 in PBMC of AS patients was low and was positively correlated with BASMI (p < 0.05), but it was not correlated with the duration of disease, age of onset, BASDAI, ESR, or BMD. CONCLUSION: Loss of bone mass mainly occurred at the inflammatory sites in AS patients, depending on the severity of inflammation. The alleviation of inflammation can improve loss of bone mass and bone metabolism disorders. Anti-inflammatory treatment is critical for the treatment of secondary osteoporosis caused by AS.

Total synthesis of (-)-4-desacetoxy-1-oxovindoline: Single atom exchange of an embedded core heteroatom in vindoline.

A concise total synthesis of (-)-4-desacetoxy-1-oxovindoline is disclosed, bearing a single heteroatom exchange in the core structure of the natural product 4-desacetoxyvindoline. Central to the synthesis is powerful oxadiazole intramolecular [4+2]/[3+2] cycloaddition cascade that formed four C-C bonds, created three new rings, and established five contiguous stereocenters about the new formed central 6-membered ring.

Ultrasound assessment of skin thickness and stiffness: the correlation with histology and clinical score in systemic sclerosis.

BACKGROUND: Ultrasound is a useful tool to evaluate and quantify skin lesions. Few studies have assessed the criterion validity of skin ultrasound in systemic sclerosis (SSc). The aims of the study were to investigate skin thickness and stiffness using ultrasound and shear wave elastography (SWE) in SSc and to validate skin ultrasound measurements against histological skin thickness. METHODS: A total of 22 patients with diffuse cutaneous SSc (dcSSc), 22 with limited cutaneous SSc (lcSSc), and 22 age- and gender-matched healthy controls were enrolled. Skin thickness and stiffness were measured by B-mode ultrasound with SWE imaging on the bilateral fingers and hands. Additional ultrasound evaluation was carried out in 13 patients (9 dcSSc and 4 lcSSc) on their dorsal forearms, followed by skin biopsy conducted in the same skin areas. Correlations between ultrasound measurements and histological skin thickness and modified Rodnan skin score (mRSS) were investigated using Spearman's correlation. RESULTS: Compared with controls, ultrasound-measured skin thickness and skin stiffness were significantly higher in patients with SSc (p < 0.001) and even higher in those with dcSSc. No clear correlation could be established between ultrasound-determined skin thickness and stiffness at the same site. Ultrasound-measured skin thickness correlated well with histological skin thickness (r = 0.6926, p = 0.009). A weaker association was also observed between histological skin thickness and local mRSS (r = 0.5867, p = 0.050). CONCLUSIONS: Ultrasound is a reliable tool for quantifying skin involvement in SSc. Ultrasound-measured skin thickness showed good agreement with histological skin thickness.

The correlation between interleukin-34 and bone erosion under ultrasound in rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory arthropathy characterized by excessive synovial hyperplasia and progressive joint destruction. Pro-inflammatory cytokines play major roles in the regulation of synovial inflammation. The contribution of interleukin-34 (IL-34) in RA pathogenesis has been strongly suggested in clinical studies.Aim: To investigate the correlation between plasma IL-34 and disease parameters in RA patients including disease activity score (DAS28), receptor activator of NF-[Formula: see text]B ligand (RANKL) concentration, synovitis and bone erosions under ultrasound.Methods: 60 RA patients and 20 healthy controls were from Huashan Hospital, patient's medical history, physical examination, laboratory examination and ultrasound data were collected and recorded, respectively. Blood samples of all participants were collected and the levels of IL-34 and RANKL were tested. The levels of IL-34 and RANKL in RA patients were compared with those of healthy controls. Furthermore, the correlation between IL-34, RANKL and disease parameters in RA patients was analyzed.Results: Both plasma levels of IL-34 and RANKL in RA patients were significantly higher than the healthy controls (p < .05). IL-34 was significantly related to disease activity scores (r = 0.43, p = .001); RANKL (r = 0.46, p = .0003) and bone erosions by ultrasound (r = 0.38, p = .002).Conclusions: The plasma IL-34 concentration in RA was significantly higher than the healthy controls and was significantly correlated with RANKL, as well as disease activity score and bone erosions by ultrasound. The IL-34 may be a new biological marker for disease activity and predictor for bone erosions in RA. Targeting IL-34 holds promise in the management of RA and, potentially, other osteoclasts driven diseases (erosive osteoarthritis and psoriatic arthritis for example).

Promotion of Myofibroblast Differentiation and Tissue Fibrosis by the Leukotriene B4 -Leukotriene B4 Receptor Axis in Systemic Sclerosis.

OBJECTIVE: To investigate the role of the inflammatory lipid mediator leukotriene B4 (LTB4 ) and its receptor, BLT1, in the development and progression of systemic sclerosis (SSc). METHODS: Serum levels of LTB4 were compared in 64 patients with SSc and 80 healthy controls. Skin and lung tissue sections from patients with SSc and healthy donors were immunostained for leukotriene A4 hydrolase (LTA4 H), the critical enzyme for LTB4 synthesis, and BLT1, in combination with different cell markers. In mouse models of SSc using bleomycin or angiotensin II challenge or immunization with the DNA topoisomerase I, genetic or pharmacologic interruption of the LTB4 -BLT1 axis in mice was carried out to assess its effects on systemic disease features and myofibroblast markers. Immunoblotting was performed to examine the signaling pathway in fibroblasts and endothelial cells following stimulation with LTB4 or with serum from SSc patients. RESULTS: Serum LTB4 levels were 44.93% higher in patients with SSc than in matched healthy controls (mean ± SD 220.3 ± 74.75 pg/ml versus 152.0 ± 68.05 pg/ml; P < 0.0001), and this was associated with the patient subsets of SSc-associated interstitial lung disease and diffuse cutaneous SSc. Levels of LTA4 H and BLT1 were increased in lesional areas of the skin and lungs of SSc patients, and both were abundant in myofibroblasts and endothelial cells. Interruption of the LTB4 -BLT1 axis in mouse models of SSc significantly mitigated dermal and pulmonary fibrosis, with 54.00% and 52.65% fewer α-smooth muscle actin-positive myofibroblasts accumulating in the skin and lungs of mice, respectively, after bleomycin challenge. Immunoblotting of cultures with recombinant LTB4 -stimulated fibroblasts and endothelial cells or with serum from SSc patients showed that fibroblast-myofibroblast and endothelial-mesenchymal transitions were promoted via BLT1, and that this was dependent on activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway but independent of the release of transforming growth factor ß (TGFß) by fibroblasts or endothelial cells. CONCLUSION: The LTB4 -BLT1 axis may contribute to fibrosis in SSc by directly promoting myofibroblast differentiation via the PI3K/Akt/mTOR pathway, and this appears to operate independently of autocrine secretion of TGFß.

Leptin facilitates the differentiation of Th17 cells from MRL/Mp-Fas lpr lupus mice by activating NLRP3 inflammasome.

Both NLRP3 inflammasome and Th17 cells play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here we tried to investigate whether leptin promotes the differentiation of Th17 cells from lupus mice by activating the NLRP3 inflammasome. Th17 cells induced from MRL/Mp-Fas lpr mice splenocytes under Th17 polarizing condition were treated with leptin at scalar doses during the last 18 h of culture. The mRNA levels of IL-17A, IL-17F, RORγt, IL-1ß, IL-18, NLRP3, ASC, and IL-1R1 were detected by quantitative PCR. IL-17A, IL-17F, IL-1ß, and IL-18 were tested by ELISA, while the activity of caspase-1 and number of Th17 cells were counted by flow cytometry before/after inhibition of the NLRP3 inflammasome. We found that leptin pushed up the expression of IL-17A, IL-17F, NLRP3, and IL-1ß and increased the number of Th17 cells in lupus mice, while the expression of IL-17A, RORγt, and IL-1ß and the number of Th17 cells were decreased after inhibition of the NLRP3 inflammasome. Leptin promoted the differentiation of Th17 cells from lupus mice by activating the NLRP3 inflammasome.

Sirt1 ameliorates monosodium urate crystal-induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway.

OBJECTIVES: Acute gout is an inflammatory response to MSU crystals. In our previous research, Sirt1 was shown to have an effect in preventing acute gouty inflammation. In the current study, we aimed to investigate the underlying mechanism involving Sirt1 in acute gout. METHODS: The cytological changes and Sirt1 expression in the synovium were observed in patients with acute or intermittent gout. The effect of Sirt1 and its mechanism in gout were studied in macrophages, C57BL/6 mice and Sirt1+/- mice. RESULTS: Sirt1 expression was increased in the peripheral blood mononuclear cells (PBMCs) of patients with acute gout but not in the chronic tophus tissue. The arthritis score and numbers of inflammatory cells in injured paw tissue from murine gout models were upregulated in Sirt1+/- mice compared with wild-type mice. A PCR array of the paw tissue from murine gout models indicated that Sirt1 activation might attenuate MSU-induced inflammation by altering the polarization state of macrophages. Furthermore, in patients with acute gout, the phagocytosis of MSU crystals by a macrophage was found in a smear of the joint fluid and large amounts of macrophages were also found in the synovium. The activation of Sirt1 in gouty mice actually decreased the tendency toward M1 polarization. The inhibition of PI3K/Akt partially blocked the anti-inflammatory effect of Sirt1 and the translocation of STAT6, and phosphorylated STAT6 expression was decreased in RAW 264.7 cells treated with MSU crystals. CONCLUSION: Our studies revealed that Sirt1 ameliorates MSU-induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway.

Leptin Promotes Monosodium Urate Crystal-Induced Inflammation in Human and Murine Models of Gout.

Gouty arthritis is an inflammatory disease that is triggered by abnormal uric acid metabolism, which is usually attributed to obesity, a risk factor of hyperuricemia and gout attack. A high level of leptin in plasma is a marker of individuals with obesity. Population studies show that leptin promotes obesity-related arthritis, such as osteoarthritis, but it is unknown whether leptin contributes to gouty arthritis, another form of obesity-related arthritis. Our present study showed that the levels of leptin and leptin receptor in patients with active gouty arthritis were elevated. Leptin facilitates the stimulation of human synoviocytes, mouse peritoneal macrophages, and HL-60 cells induced by monosodium urate, leading to higher levels of acute gout-related proinflammatory factors. Leptin obviously exacerbates the inflammation of monosodium urate-induced acute gouty arthritis in wild-type mice, whereas that in leptin-deficient C57BL6/Job/ob mice is markedly alleviated. The proinflammatory effect of leptin in acute gouty arthritis is partly mediated by mTORC1 signaling pathway. Our study reveals that leptin may serve as a novel prevention and treatment target in acute gouty arthritis.

Associations of circulating CXCR3-PD-1+CD4+T cells with disease activity of systemic lupus erythematosus.

OBJECTIVES: Which helper CD4+ T cell subset contributes to autoantibodies generation and severity of end-organ involvement in lupus patients remains to be explored. Our research aims to investigate the roles of circulating Tfh (cTfh) cell subsets and corresponding CXCR5- Th cells in lupus patients and their correlation with SLE disease activity index 2000 (SLEDAI). METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from blood of systemic lupus erythematosus (SLE) patients as well as healthy donors. The proportion of Th cell subsets classified from cell surface markers (CD45RO, CXCR5, CXCR3, CCR6, PD-1, ICOS, and CCR7) is detected by flow cytometry. RESULTS: We found no difference in the frequency of CD45RO+CXCR5+CD4+ T cells between SLE patients and health controls. As previously reported, SLE patients showed an increase in the percentage of CXCR5+PD-1+, CXCR5+ICOS+PD-1+ and CXCR5+CCR7loPD-1hi cTfh subset, however, none of these populations had correlation with SLEDAI. Therefore, we further investigated the CXCR5- subsets, and surprisingly we found that the frequency of CXCR3-PD-1+ subset was correlated with SLEDAI, ds-DNA IgG, anti-nucleosome antibody, C3, and C4 independent of CXCR5. Consistently, CXCR3-PD-1+CD45RO+CD4+T cells expressed factors associated with B-cell-help for the autoantibody production. CONCLUSION: CXCR3-PD-1+CD4+T cells are a sensitive indicator to assess SLE disease activity and might contribute B cell help and the generation of autoantibodies in patients.

Leptin promotes IL­18 secretion by activating the NLRP3 inflammasome in RAW 264.7 cells.

Leptin is a cytokine­like hormone secreted by adipocytes, which serves to control energy expenditure and metabolism. In addition, leptin may modulate the innate and adaptive immune responses. The innate immune cell sensor nucleotide­binding oligomerization domain­like receptor family pyrin domain­containing 3 (NLRP3) inflammasome is mainly expressed in myeloid immune cells, including macrophages. The NLRP3 inflammasome serves a pivotal role in the development and maintenance of autoimmunity and inflammation. The expression levels of caspase­1, apoptosis­associated speck­like protein containing a CARD, interleukin (IL)­18, IL­1ß and leptin are significantly reduced in the white adipose tissue of nonsteroidal anti­inflammatory drug­activated gene­1 transgenic mice. However, the association between leptin and the NLRP3 inflammasome has not yet to be determined. The aim of the present study, was to explore the role of leptin on NLRP3 inflammasome. In order to do this, IL­1ß and IL­18 expression levels were investigated in RAW 264.7 cells after incubation with leptin of increasing doses by Elisa or reverse transcription­quantitative polymerase chain reaction, and to assess whether IL­1ß and IL­18 were affected after caspase­1 activity being inhibited by an inhibitor or by silencing NLRP3 expression. The results of the present study demonstrated that leptin enhanced the mRNA and protein expression levels of IL­18 in RAW 264.7 cells via activation of the NLRP3 inflammasome. This is achieved partly by enhancing the production of reactive oxygen species and K+ efflux. Therefore, leptin may be considered a novel activator and modulator of the NLRP3 inflammasome.

New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions.

OBJECTIVES: New interleukins (ILs), especially members of IL-1 and IL-12 families, have recently been reported to be involved in the development and regulation of autoimmune and inflammatory diseases. In this study, we aimed to explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis (PsA). METHODS: Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs) were recruited. Blood samples were obtained for detecting the levels of ILs, IL-12/23p40, and tumor necrosis factor α (TNF-α). The severity of skin lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and receptor activator of nuclear factor-κB ligand) and numbers of osteoclast precursors were evaluated. Radiographic features of affected joints in these patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Correlations among levels of these ILs, Ps, and PsA disease activities and bone erosions were studied. RESULTS: Ps and PsA patients had higher serum levels of TNF-α, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had higher serum levels of IL-36α and IL-38 than patients with Ps vulgaris or HCs. Increased serum levels of IL-36α were positively correlated with PASI. CONCLUSION: Certain ILs were elevated in the circulation of patients with Ps and PsA, which might contribute to the pathogenesis of skin lesions and arthritis.

Clinical Association of Chemokine (C-X-C motif) Ligand 1 (CXCL1) with Interstitial Pneumonia with Autoimmune Features (IPAF).

The term "interstitial pneumonia with autoimmune features" (IPAF) has been recently proposed. We here investigate the clinical characteristics of IPAF and evaluate the clinical implications of CXCL1-CXCR2 axis in IPAF. An increased plasma level of CXCL1 was exhibited in IPAF compared to idiopathic interstitial pneumonia (IIP), chronic obstructive pulmonary disease (COPD), and healthy controls. Additionally, plasma CXCL1 levels were clinically associated with diffusing capacity of the lungs for carbon monoxide (DLCO), erythrocyte sedimentation rate (ESR), and involved parenchyma extension in IPAF. Furthermore, circulating CXCL1 levels were highest in IPAF patients with acute exacerbations. CXCR2, the chemokine receptor for CXCL1, was readily observed in inflammatory aggregates and endothelial cells in IPAF lungs, but was lower in IIP lungs and healthy lungs. Interestingly, increased CXCL1 concentrations in BALF paralleled neutrophil counts in IPAF. Overall, the plasma concentrations of CXCL1 indicated the disease activity and prognosis in IPAF. Thus, the CXCL1/CXCR2 axis appears to be involved in the progression of IPAF.