Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome (NLRP3, ASC, and CASP1) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. Results: We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p=0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p=0.0001 for Caspase-1 and an AUC of 0.665 with p=0.0139 for ASC to MDS discrimination. Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested.

In this study, we investigated the levels of interleukin-1β (IL-1β), IL-18, and the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome in patients with premature rupture of membranes (PROMs).
We selected 60 pregnant women at the Fourth Hospital of Baotou between January 2019 and July 2021. These women were divided into three distinct groups: the preterm PROM group with 20 cases, term PROM (TPROM) group with 20 cases, and a control group with 20 cases consisting of normal full-term pregnancies without PROM. Peripheral blood was collected from all participants. Using enzyme-linked immunosorbent assay, the levels of IL-1 and IL-18 in the plasma were assessed. Additionally, the proportions of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1-positive macrophages were also evaluated.
The ratios of NLRP3, ASC, IL-1β, and IL-18 concentrations, along with the presence of caspase-1-positive macrophages, were notably greater in the PROM groups in comparison with the control group (p < .05). In the TPROM group and control group, the proportions of IL-1β and IL-18 levels were found to be lower than NLRP3, ASC, and caspase-1-positive macrophages levels (p < .05).
The concentrations of IL-1β and IL-18, as well as the ratios of NLRP3, ASC, and caspase-1-positive macrophages, were elevated in patients with PROM compared to the control group. This suggests a potential correlation between the excessive activation of NLRP3 and the development of PROM.

Parkinson\'s disease (PD) is a neurodegenerative disorder marked by the death of dopaminergic neurons in the midbrain, the accumulation of α-synuclein aggregates, and motor deficits. A major contributor to dopaminergic neuronal loss is neuroinflammation. The inflammasome is a multiprotein complex that perpetuates neuroinflammation in neurodegenerative disorders including PD. Increases in inflammasome proteins are associated with worsened pathology. Thus, the inhibition of inflammatory mediators has the potential to aid in PD treatment. Here, we investigated inflammasome signaling proteins as potential biomarkers of the inflammatory response in PD. Plasma from PD subjects and healthy age-matched controls were evaluated for levels of the inflammasome protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin (IL)-18. This was carried out using Simple Plex technology to identify changes in inflammasome proteins in the blood of PD subjects. The area under the curve (AUC) was obtained through calculation of the receiver operating characteristics (ROC) to obtain information on biomarker reliability and traits. Additionally, we completed a stepwise regression selected from the lowest Akaike information criterion (AIC) to assess how the inflammasome proteins caspase-1 and ASC contribute to IL-18 levels in people with PD. PD subjects demonstrated elevated caspase-1, ASC, and IL-18 levels when compared to controls; each of these proteins were found to be promising biomarkers of inflammation in PD. Furthermore, inflammasome proteins were determined to significantly contribute to and predict IL-18 levels in subjects with PD. Thus, we demonstrated that inflammasome proteins serve as reliable biomarkers of inflammation in PD and that inflammasome proteins provide significant contributions to IL-18 levels in PD.

UNASSIGNED: Heart failure complicating acute coronary syndrome (ACS) remains a challenge because it is associated with a high risk of mortality at 1 year.Our objective is to highlight the factors frequently associated with heart failure following an ACS and thus deduce the predictive factors for the occurrence of heart failure.
UNASSIGNED: ACS patients who were managed between 01/01/2021 to 06/30/2021 at the authors\' institution were included retrospectively in the analysis.
UNASSIGNED: One hundred twenty-one patients (121) included. Eighty-seven were males (72%), and the mean age was 59.4 ± 8.8. Most patients were smokers (58.7%),40% were diabetic, and 40.5% were hypertensive. Dyslipidemia was found in 37.2% of cases. 75% of patients were admitted for STEMI, and 25% for NSTEMI. The majority of patients (67.5%) were admitted out of time. The anterior electrical territory was found as a factor in the occurrence of heart failure (OR = 5.47, 95% CI (2.16-15.26), P = 0.0005). Among the patients who presented a heart failure, 64% had an LVEF <40%, and only 3% with an LVEF >50% (P < 0.001). Also, 76% had a Wall Motion Index Score (WMSI) of 1.5 (P < 0.001). Angioplasty was the treatment of choice in 65%, aortocoronary bypass in 7% of cases, and medical treatment alone, associated or not with ischemia/viability tests in 28% of cases. Patients admitted out of time (>12 h) were found to be a factor in the occurrence of HF (OR = 3.31,95% CI (1.21-10,60), P = 0.02). The outcome was favorable in 93% of cases. We observed 9 cases of complications including 4 deaths from cardiogenic, septic, and hemorrhagic shock.
UNASSIGNED: This study allows us to identify patients at risk of developing heart failure and patients with a more reserved prognosis. Besides, our findings will allow our peers and colleagues to be able to detect early these factors and optimize adequate management to avoid heart failure.

BACKGROUND: In the last decades, autologous fat grafting has been used to treat adherent dermal scars. The observed regenerative and scar-reducing properties have been mainly ascribed to the tissue-derived stromal vascular fraction (tSVF) in adipose tissue. Adipose tissue\'s components augment local angiogenesis and mitosis in resident tissue cells. Moreover, it promotes collagen remodeling. We hypothesize that tSVF potentiates fat grafting-based treatment of adherent scars. Therefore, this study aims to investigate the effect of tSVF-enriched fat grafting on scar pliability over a 12-month period.
METHODS: A clinical multicenter non-randomized early phase trial will be conducted in two dedicated Dutch Burn Centers (Red Cross Hospital, Beverwijk, and Martini Hospital, Groningen). After informed consent, 46 patients (≥18 years) with adherent scars caused by burns, necrotic fasciitis, or degloving injury who have an indication for fat grafting will receive a sub-cicatricic tSVF-enriched fat graft. The primary outcome is the change in scar pliability measured by the Cutometer between pre- and 12 months post-grafting. Secondary outcomes are scar pliability (after 3 months), scar erythema, and melanin measured by the DSM II Colormeter; scar quality assessed by the patient and observer scales of the Patient and Observer Scar Assessment Scale (POSAS) 2.0; and histological analysis of scar biopsies (voluntary) and tSVF quality and composition. This study has been approved by the Dutch Central Committee for Clinical Research (CCMO), NL72094.000.20.
CONCLUSIONS: This study will test the clinical efficacy of tSVF-enriched fat grafting to treat dermal scars while the underlying working mechanism will be probed into too.
BACKGROUND: Dutch Trial Register NL 8461. Registered on 16 March 2020.

UNASSIGNED: Immunoglobulin A (IgA) nephropathy is a disease that presents with urinary symptoms such as glomerular hematuria and urinary protein positivity, with predominant deposition of IgA in the mesangial region of the glomerulus. Corticosteroids are mainly used for treatment; however, infection is a serious adverse event, and evidence regarding therapeutic efficacy is insufficient, thus new treatments are strongly desired. Mesenchymal stem cells (MSCs) contribute to the amelioration of inflammation and recovery of organ function in inflammatory environments by converting the character of leukocytes from inflammatory to anti-inflammatory and inducing the proliferation and differentiation of organ component cells, respectively. These properties of MSCs have led to their clinical application in various inflammatory diseases, but this study is the first clinical trial of MSCs for refractory glomerulonephritis in the world. This study is registered and assigned the number, jRCT2043200002 and NCT04342325.
UNASSIGNED: This will be a phase 1, open-label, multiple-center, dose-escalation study of adult patients with refractory IgA nephropathy resistant to or difficult to treat with existing therapies. ADR-001 will be administered intravenously to from three to six patients at a dose of 1 × 108 cells once in the first cohort and to six patients twice at 2-week intervals in the second cohort, and observation will continue until 52 weeks. The primary endpoint will be the evaluation of adverse events up to 6 weeks after the start of ADR-001 administration. Secondary endpoints will be the respective percentages of patients with adverse events, clinical remission, partial remission, remission of urine protein, remission of hematuria, time to remission, changes in urine protein, hematuria, and estimated glomerular filtration rate.
UNASSIGNED: Following the administration of ADR-001 to patients with IgA nephropathy, the respective percentages of patients with adverse events, asymptomatic pulmonary emboli, clinical remission, partial remission, urine protein remission, hematuria remission, their time to remission, changes in urine protein, hematuria, and glomerular filtration rate will be determined.
UNASSIGNED: This study will evaluate the safety and tolerability of ADR-001 and confirm its therapeutic efficacy in adult patients with refractory IgA nephropathy.

OBJECTIVE: Randomised controlled trial (RCT) in adults with anorexia nervosa (AN) showed that Cognitive Remediation Therapy (CRT) enhances cognitive flexibility, abstract thinking and quality-of-life. Despite inconsistent findings, CRT has the potential as an adjunct treatment for young people (YP) with AN. A feasibility RCT was conducted in an inpatient setting. The study will also consider the effect of CRT in YP with AN and autistic symptoms.
METHODS: Participants were randomly allocated to the Immediate or Delayed condition to receive individual CRT sessions, in addition to standard treatment. A repeated measures design was conducted.
RESULTS: Eighty participants were recruited. The neuropsychological measures were feasible for evaluating individual CRT in YP. Significant improvements in set-shifting and central coherence were found, with no main effect between immediate and delayed condition. Significant interactions were found between the condition, and autism spectrum condition (ASC) and No-ASC subgroup, with significant positive impact of CRT on set-shifting in the No-ASC subgroup. There was some evidence that for the No-ASC subgroup, CRT was more effective if delivered at the start of the treatment; and for the ASC subgroup, that CRT was more effective if delivered at the later stage of treatment.
CONCLUSIONS: These findings suggest that the overall positive effect of CRT in set-shifting and central coherence alongside standard treatment. They also indicate the importance of screening for the presence of ASC which could require tailored CRT.

Neuroinflammation is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer\'s disease (AD), and is notably dependent on age. One important inflammatory pathway exerted by innate immune cells of the nervous system in response to danger signals is mediated by inflammasomes (IF) and leads to the generation of potent pro-inflammatory cytokines. The protein \"apoptosis-associated speck-like protein containing a caspase recruitment domain\" (ASC) modulates IF activation but has also other functions which are crucial in AD. We intended to characterize immunohistochemically ASC and pattern recognition receptors (PRR) of IF in the hippocampus (HP) of the transgenic mouse model Tg2576 (APP), in which amyloid-beta (Aβ) pathology is directly dependent on age. We show in old-aged APP a significant amount of ASC in microglia and astrocytes associated withAβ plaques, in the absence of PRR described by others in glial cells. In addition, APP developed foci with clusters of extracellular ASC granules not spatiallyrelated to Aβ plaques, which density correlated with the advanced age of mice and AD development. Clusters were associated withspecific astrocytes characterized by their enlarged ring-shaped process terminals, ASC content, and frequent perivascular location. Their possible implication in ASC clearance and propagation of inflammation is discussed.

Perianal fistula is one of the most common complications in Crohn\'s disease, and various medical and surgical treatments are being tried. The aim of this study was to compare the perianal fistula closure rates following treatment with anti-tumor necrosis factor (TNF) agents or autologous adipose tissue-derived stem cell (auto-ASC) transplantation with Crohn\'s disease (CD).
CD patients who underwent seton placement for perianal fistula from January 2015 to December 2019 at a tertiary referral center were retrospectively reviewed. Patients were divided into two groups, one that received sequential treatments with anti-TNF agents (anti-TNF group) and the other that underwent auto-ASC transplantation (stem cell group). Clinical variables and fistula closure rates were compared in the two groups.
Of the 69 patients analyzed, 39 were treated with anti-TNF agents and 30 underwent auto-ASC transplantation. Compared with the stem cell group, patients in the anti-TNF group were older (p=0.028), were more frequently male (p=0.019), had fistulas with more penetrating behavior (p=0.002), had undergone surgery more frequently (p=0.010), and had a shorter interval from seton placement to intended treatment (p<0.001). During a median follow-up of 46 months (range, 30-52.5 months), fistula closure rates were significantly faster (83.3% vs. 23.1%, p<0.001), and the mean interval from seton placement to fistula closure significantly shorter (14 vs. 37 months, p<0.001) in the stem cell than in the anti-TNF group. Three patients experienced fistula recurrence, all in the stem cell group.
Medical treatment using anti-TNF agents and auto-ASC transplantation are feasible treatment options after seton placement for Crohn\'s perianal fistula. However, the closure rate was significantly faster and the time to closure significantly shorter in patients who underwent auto-ASC transplantation than medical treatment.
This study was retrospectively registered and approved by the Institutional Review Board of Asan Medical Center, number 2020-1059 .

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease that is growing in prevalence. Symptoms of NASH become apparent when the disease has progressed significantly. Thus, there is a need to identify biomarkers of NASH in order to detect the disease earlier and to monitor disease severity. The inflammasome has been shown to play a role in liver diseases. Here, we performed a proof of concept study of biomarker analyses (cut-off points, positive and negative predictive values, receiver operating characteristic (ROC) curves, and likelihood ratios) on the serum of patients with NASH and healthy controls on apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18, Galectin-3 (Gal-3), and C-reactive protein (CRP). ASC, IL-18, and Gal-3 were elevated in the serum of NASH patients when compared to controls. The area under the curve (AUC) for ASC was the highest (0.7317) with an accuracy of 68%, followed by IL-18 (0.7036) with an accuracy of 66% and Gal-3 (0.6891) with an accuracy of 61%. Moreover, we then fit a stepwise multivariate logistic regression model using ASC, IL-18, and Gal-3 to determine the probability of patients having a NASH diagnosis, which resulted in an AUC of 0.71 and an accuracy of 79%, indicating that combining these biomarkers increases their diagnostic potential for NASH. These results indicate that ASC, IL-18, and Gal-3 are reliable biomarkers of NASH and that combining these analytes increases the biomarker potential of these proteins.