Pyroptosis burden is associated with anti-TNF treatment outcome in inflammatory bowel disease: new insights from bioinformatics analysis.

Biological agents known as anti-tumor necrosis factor (TNF) drugs are frequently utilized in the treatment of inflammatory bowel disease (IBD). In this study, we analyzed the shared processes of pyroptosis in Ulcerative colitis (UC) and Crohn's disease (CD), as well as explored the correlation between the burden of pyroptosis and the results of anti-TNF treatment based on bioinformatics analyses. We identified CAPS1, CASP5, GSDMD, AIM2, and NLRP3 as the hub genes, with AIM2 being the most effective indicator for predicting the response to anti-TNF therapy. We also noticed that non-responders received anti-TNF therapy exhibited elevated AIM2 protein expression. Subsequently, we conducted a cluster analysis based on AIM2-inflammasome-related genes and discovered that patients with a higher burden of AIM2 inflammasome displayed stronger immune function and a poor response to anti-TNF therapy. Overall, our study elucidates the pathway of pyroptosis in IBD and reveals AIM2 expression level as a potential biomarker for predicting the effectiveness of anti-TNF therapy.

[Pollution Characteristics and Removal Effects of Antibiotics in Wastewater from Large-Scale Pig Farms in Guizhou].

To understand the pollution characteristics and removal effect of antibiotics in the wastewater treatment process of large-scale pig farms in Guizhou, solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS) was used to investigate the removal of ten veterinary antibiotics from the influent and effluent of each treatment unit during the wastewater treatment process in two large-scale pig farms (named Farm A and Farm B). The results showed that the removal rates of conventional pollutants[including chemical oxygen demand (COD), NH4+-N, total nitrogen (TN), and total phosphorus (TP)] in Farm A and Farm B were above 88.10%. The antibiotics concentrations detected in the influent and effluent ranged from ND-120842.74 ng·L-1. The main antibiotics were sulfamonomethoxine (SMM), sulfamethoxazole (SMD), oxytetracycline (OTC), and ofloxacin (OFL), and the SMM concentration was highest at 120842.74 ng·L-1. The removal rate of the ten antibiotics was 99.23%-100.00% in Farm A and Farm B. In the wastewater treatment process of Farm A, the treatment section "USR+2A/O+disinfection pond+oxidation pond" removed antibiotics in wastewater effectively, with the total removal rate of SMM, SMD, and OTC reaching 100.00%. In the wastewater treatment process of Farm B, the treatment section "ultrafiltration (UF)+nanofiltration (NF)" removed antibiotics effectively by more than 99.23%. However, the concentrations of antibiotics investigated in the effluent were higher than the EU water environment antibiotic threshold (10 ng·L-1). Finally, through redundancy analysis, it was found that conventional indicators (COD, NH4+-N, TN, TP, and pH) in wastewater were related to the degradation of some antibiotics.

[Correlation of C-MYC Protein, MDSC and Th17 Cells with Pathogenesis of Myeloma in Different Clinical Stages].

OBJECTIVE: To investigate the correlation of C-MYC protein with MDSC, Th17 cells and the pathogenesis of myeloma in different clinical stages. METHODS: A total of 65 patients with multiple myeloma treated in our hospital were selected as MM group, and 30 healthy subjects were selected as control group. The positive expression rate of C-MYC protein in bone marrow tissue, and the ratios of peripheral blood MDSC and Th17 cells were compared among the two groups, and the correlation of C-MYC protein, the ratio of MDSC, Th17 cells with onset of myeloma at different clinical stages, the relationship of the expression of C-MYC protein with the ratio of MDSC/Th17 cells and the clinical parameters of MM was analyzed. Also, the diagnostic value of single diagnosis and combined diagnosis was compared. RESULTS: The positive expression rate of C-MYC protein in bone marrow, the ratio of MDSC and Th17 cells in peripheral blood in MM group were significantly higher than those in normal control group(P＜0.05); the positive expression rate of C-MYC protein, MDSC and Th17 cells in patients at ISS stage Ⅰ, Ⅱ and Ⅲ MM showed an increasing trend (r=0.432, r=0.401, r=0.351); the correlation between the ratio of MDSC, Th17 cells and the positive expression rate of C-MYC protein in MM patients was positive (r=0.415, r=0.417); the area under ROC curve (AUC) of combined diagnosis was significantly larger than that of single index diagnosis (C-MYC protein, MDSC cells, Th17 cells)(P＜0.05). There was no correlation between the expression of C-MYC protein, the proportion of MDSC, Th17 cells and sex or age in MM patients (P＞0.05). CONCLUSION: The positive expression rate of C-MYC protein and the proportion of MDSC and Th17 cells in MM patients significantly increase, which positively correlates with clinical ISS stagin.

Serum exosomal microRNAs as novel biomarkers for multiple myeloma.

Accumulating studies have focused on circulating microRNAs, which might be potential biomarkers for different malignancies. The aim of this study was to investigate the potential of serum exosomal microRNAs to be novel serum biomarkers for smouldering myeloma (SMM) or even multiple myeloma (MM). The levels of serum exosomal microRNAs and serum circulating microRNAs were measured in healthy individuals and patients with SMM (n = 20) or MM (n = 20). Serum exosomal microRNAs and serum circulating microRNAs were extracted from serum, and the expression levels of selected microRNAs were quantified by real-time polymerase chain reaction (PCR). The levels of serum exosome-derived miR-20a-5p, miR-103a-3p, and miR-4505 were significantly different among patients with MM, patients with SMM, and healthy individuals, while there were differences in the levels of let-7c-5p, miR-185-5p, and miR-4741 in patients with MM relative to those in SMM patients or healthy controls. Additionally, a significant correlation was rarely found between the levels of serum and exosomal microRNAs. This study shows that serum exosomal microRNAs can be used independently as novel serum biomarkers for MM.

Potential Relationship between Clinical Significance and Serum Exosomal miRNAs in Patients with Multiple Myeloma.

This study evaluated the potential relationship between exosomal miRNAs and clinical symptoms in patients with multiple myeloma (MM). Forty-eight newly diagnosed myeloma patients and sixteen normal donors were enrolled in the study. The results showed that the relative expression levels of let-7c-5p, let-7d-5p, miR-140-3p, miR-185-5p, and miR-425-5p in the exosomes of MM patients were significantly lower than those of healthy controls. Furthermore, there were significant differences in the clinical characteristics of myeloma, such as kidney damage, while the expression levels of the same miRNA in exosomes and serum are not correlated. The expression of exosomal miRNA is related to the expression levels of clinical feature-related factors, such as creatinine, ß2-microglobulin, ß-CTX, and IL-6 in serum. Establishing this relationship could contribute to understanding the pathogenesis of MM.

Autoantibodies against ß1-adrenergic receptor: response to induction therapy with bortezomib-containing regimens for multiple myeloma patients.

This study aims to investigate the predictive value of pre-chemotherapy ß1R-AABs by evaluating the response of newly diagnosed symptomatic multiple myeloma (MM) patients to their treatment with a bortezomib-containing regimen. Forty-five de novo MM patients and 50 normal controls (NCs) were prospectively enrolled in this study. Serum titers of ß1R-AABs were detected by ELISA. These 45 MM patients were divided into two groups (positive and negative groups) according to their ß1R-AABs. Follow-up examinations were performed on these patients during chemotherapy induction. The final analysis covered all 45 MM patients, including 19 patients who were positive for MM and 26 patients who were negative for MM. Multivariate analysis revealed that pre-chemotherapy ß1R-AABs are possibly independent predictors for less than very good partial response (VGPR) after the bortezomib-containing regimen treatment (odds ratio: 5.967, 95% confidence interval: 1.513-23.531; p = .011). This study demonstrates for the first time that the presence of ß1R-AABs is associated with MM. Pre-chemotherapy ß1R-AABs are independent predictors for less than VGPR in de novo MM patients after the bortezomib-containing regimen was administrated. Bortezomib might not significantly give rise to cardiac impairment in MM patients.

Mixed lineage leukemia-septin 5 fusion transcript in de novo adult acute myeloid leukemia with t(11;22)(q23;q11.2): A case report.

The current report presents a case of de novo acute myeloid leukemia (AML) in a 32-year-old male. Cytogenetic analysis showed that the karyotype of the bone marrow cells was as follows: 46,XY,t(11;22)(q23;q11.2)[13]/46,X,-Y,+10,t(11;22)(q23;q11.2)[7]/47,XY,+10,t(11;22)(q23;q11.2)[1]/46,XY[1]. Fluorescence in situ hybridization analysis using a mixed lineage leukemia (MLL)-specific probe showed a split in the MLL gene. Reverse transcription polymerase chain reaction (PCR) analysis demonstrated an MLL-septin 5 (SEPT5) fusion transcript in the patient. Nucleotide sequencing analysis of the PCR product confirmed the fusion between the MLL exon 9 and SEPT5 exon 3, and the product was 521 bp in length. The present study reviewed the clinical and molecular features of the AML with an MLL-SEPT5 fusion gene.

Differential protein expression profile between CD20 positive and negative cells of the NCI-H929 cell line.

At present, multiple myeloma (MM) remains an incurable disease and cologenic cells may be responsible for disease relapse. It has been proposed that CD20+/CD138- NCI-H929 cells could be hallmarks of MM clonogenic cells. Here, the immunology phenotype of NCI-H929 cells is described. Only a small population of CD20+/CD138- cells (<1%) was found in the NCI-H929 cell line, but CD20+/CD138- cells were not detected. We found that CD20+/CD138+ cells were able to exhibit cologenic capacity by colony formation assay and continuous passage culture. Proteins were analyzed by 1D-SDS-PAGE and TMT based quantitative differential liquid chromatography tandem mass spectrometry (LC-MS/MS). 1,082 non-redundant proteins were identified, 658 of which were differentially expressed with at least a 1.5-fold difference. 205 proteins in CD20+ cells were expressed at higher levels and 453 proteins were at lower levels compared with CD20- cells. Most proteins had catalytic and binding activity and mainly participated in metabolic processes, cell communication and molecular transport. These results proved that there are different biological features and protein expression profile between CD20+ and CD20- cells in the NCI-H929 cell line.