Pyroptosis has attracted attention due to its role in various cancers. Recently, gasdermins (GSDMs) involved in pyroptosis have been reported to be associated with several types of cancers. However, the role of GSDMs expression in the diagnosis and prognosis of gastric cancer (GC) is still not well understood. We analyzed the transcriptional and prognostic information and the role of GSDMs in patients with GC from TIMER, UALCAN, Human Protein Atlas (HPA), GEPIA, and Kaplan-Meier Plotter databases. The cBioPortal platform was used to discover the genetic alterations, significance, and networks of GSDMs. Furthermore, STRING, Cytoscape, and TIMER were used to explore functional enrichment and immunomodulation. GSDMB, GSDMC, GSDMD, and GSDME were more highly expressed in GC than in normal tissues in the TIMER database. Moreover, survival analyses in two databases showed that high expression of GSDME was related to shorter overall survival (OS) in patients with GC. Additionally, functional enrichment revealed that GSDMs may be involved in endopeptidase activity, peptidase regulatory activity, and cysteine peptidase activity. GSDMs correlated with infiltration levels of immune cells in GC, and GSDME correlated with the infiltrating level of CD4+ T, CD8+ T, neutrophils, macrophages, and dendritic cells. This study indicated the potential diagnostic and prognostic value of GSDMs in GC. Our results showed that GSDME could play a significant oncogenic role in GC diagnosis and prognosis. However, our bioinformatics analyses should be validated in further prospective studies. cancers Recently (GSDMs However (GC understood UALCAN HPA, HPA , (HPA) GEPIA KaplanMeier Kaplan Meier alterations significance Furthermore STRING Cytoscape immunomodulation GSDMB GSDMC GSDMD database Moreover OS (OS Additionally activity CD4 CD T CD8 neutrophils macrophages studies (HPA

Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.

Abstract Recently, the rs1042713 G > A and rs1042714 C > G polymorphisms in the beta-2 adrenergic receptor (ADRB2) gene were shown to be related to atherosclerosis diseases. Therefore, we performed a systemic meta-analysis to determine whether the two functional polymorphisms are related to the risk of myocardial infarction (MI) and coronary artery disease (CAD). We identified published studies that are relevant to our topic of interest. Seven case-control studies, with a total of 6,843 subjects, were incorporated into the current meta-analysis. Our analysis showed a higher frequency of rs1042713 G > A variant in patients with MI or CAD compared to healthy controls. A similar result was also obtained with the rs1042714 C > G variant under both the allele and dominant models. Ethnicity-stratified subgroup analysis suggested that the rs1042714 C > G variant correlated with an increased risk of the two diseases in both Asians and Caucasians, while rs1042713 G > A only contributes to the risk of two diseases in Asians. In the disease type-stratified subgroups, the frequencies of both the rs1042713 G > A and rs1042714 C > G variants were higher in the cases than in the controls in both the MI and CAD subgroups. Collectively, our data contribute towards understanding the correlation between the rs1042713 G > A and rs1042714 C > G polymorphisms in ADRB2 and the susceptibility to MI and CAD.

Four kinds of neutral and alkaline protease genes from Aspergillus oryzae and Bacillus subtilis were isolated and shuffled. The shuffled genes were selected, inserted into pGAPZαA plasmid and transformed into Escherichia coli. The gene which could express high-activity protease was selected by screening the sizes of transparent zones around the colonies on casein plates. After an ideal protease gene was selected, it was sequenced and then transformed into Pichia pastoris X33. The result showed that the base in 1022th position of shuffled protease gene was changed from thymine to cytosine, inferring that cysteine was changed to arginine in the mutant protease. After 48 h incubation for the transformed P. pastoris with the mutant or native protease genes, the mutant protease activity was 36.4% higher than the native protease (P<0.05). The optimal pH and temperature of the mutant protease were 6.5-8.0 and 30-70°C, respectively, which indicated better stability than the native protease (P<0.05).

BACKGROUND: Human amnion mesenchymal cells (hAMCs), isolated from the amniotic membrane of human placenta, are a unique population of mesenchymal stem cells. Recent studies demonstrated that hAMCs could inhibit the activities and functions of several immune cells. However, their effect on inflammatory macrophages is largely unknown. This study investigated the effect of hAMCs on expression of inflammatory cytokines and mitogen-activated protein kinases (MAPKs)/NF-kB pathway in human THP-1 macrophages induced by lipopolysaccharide (LPS RESULTS: The levels of TNF-α and IL-1β secreted by LPS- stimulated THP-1 cells were increased significantly compared with those in the control group. After co-culture with different numbers of hAMCs, the levels of TNF-α and IL-1β in LPS-stimulated THP-1 cells were significantly reduced compared with the LPS group. The mRNA expression of TNF-α and IL-1β were also markedly inhibited. Moreover, treating LPS-stimulated THP-1 cells with hAMCs supernatants could also suppress TNF-α and IL-1β production in THP-1 cells. Important signaling pathways involved in the production of TNF-α and IL-1β were affected by hAMCs co-culture: hAMCs remarkably suppressed NF-kB activation and down-regulated the phosphorylation of ERK and JNK in LPS- stimulated THP-1 cells CONCLUSIONS: Human amnion mesenchymal cells inhibited the production of TNF-α and IL-1β secreted by LPS-stimulated THP-1 cells, partly through the suppression of NF-kB activation and ERK and JNK phosphorylation

Lupus peritonitis (LP) is extremely rare. Acute LP is characterized by rapid onset of ascites and severe abdominal pain, in addition to other well-recognized clinical features of a general systemic lupus erythematosus (SLE) fare. Ascites associated with acute LP has been rarely reported as the prominent feature of a SLE fare. We report a 39-year-old woman who developed massive, painful ascites as the presenting manifestation of a SLE fare. Diagnostic workup ruled out the possibility of hepatic, cardiovascular, infectious, or malignant diseases, and confirmed the presence of a SLE fare. The patient was treated with methyl prednisolone and hydroxychloroquine resulting in dramatic improvement of her condition. During ambulatory follow up, she has remained asymptomatic up to the moment of this writing. Adrenal steroids and hydrocychloroquine may be useful for the management of SLE fares in patients with massive, painful ascites due to acute LP.

La peritonitis lúpica es rara. El cuadro agudo se caracteriza por ascitis de comienzo rápido, dolor abdominal severo y otras manifestaciones de una recidiva de un lupus eritematoso sistémico (LES). Sólo ocasionalmente e ha informado que la ascitis y peritonitis lúpica sean las principales manifestaciones de una recidiva lúpica. Presentamos a una mujer de 39 años que presentó ascitis masiva y dolorosa como la primera manifestación de una reactivación lúpica. El estudio diagnóstico descartó problemas hepáticos, pulmonares, cardiacos, cáncer o infecciones y confirmó la reactivación lúpica. La paciente se trató con metilprednisolona y cloroquina, resultando en una mejoría dramática. Al momento de preparar este informe, la paciente permanece asintomática en control ambulatorio. Los corticoides y cloroquina pueden ser medicamentos útiles para el tratamiento de pacientes con ascitis dolorosa y masiva secundaria a peritonitis lúpica.

Multidrug resistance (MDR) poses a serious impediment to the success of chemotherapy for laryngeal cancer. To identify microRNAs and mRNAs associated with MDR of human laryngeal cancer Hep-2 cells, we developed a multidrug-resistant human laryngeal cancer subline, designated Hep-2/v, by exposing Hep-2 cells to stepwise increasing concentrations of vincristine (0.02-0.96'µM). Microarray assays were performed to compare the microRNA and mRNA expression profiles of Hep-2 and Hep-2/v cells. Compared to Hep-2 cells, Hep-2/v cells were more resistant to chemotherapy drugs (∼45-fold more resistant to vincristine, 5.1-fold more resistant to cisplatin, and 5.6-fold more resistant to 5-fluorouracil) and had a longer doubling time (42.33±1.76 vs 28.75±1.12'h, P<0.05), higher percentage of cells in G0/G1 phase (80.98±0.52 vs69.14±0.89, P<0.05), increased efflux of rhodamine 123 (95.97±0.56 vs 12.40±0.44%, P<0.01), and up-regulated MDR1 expression. A total of 7 microRNAs and 605 mRNAs were differentially expressed between the two cell types. Of the differentially expressed mRNAs identified, regulator of G-protein signaling 10, high-temperature requirement protein A1, and nuclear protein 1 were found to be the putative targets of the differentially expressed microRNAs identified. These findings may open a new avenue for clarifying the mechanisms responsible for MDR in laryngeal cancer.

Nonylphenol ethoxylates (NPEOs), which are widely used for industrial and domestic purposes, exert adverse effects on wildlife after being used and discharged into the environment. However, their ultimate biodegradability and biodegradation pathway remains unclear. In this study, the aerobic degradability of nonylphenol ethoxylates (NPEOs) by the acclimated microorganisms in active sludge was examined using shaking-flask tests. The degradation of benzene rings in NPEOs was determined using UV spectroscopy and high performance liquid chromatography (HPLC). Results showed that more than 80% of benzene rings were removed after 8-10 days of degradation, and the majority of NPEOs were also removed after 9 days of degradation, indicating NPEOs and the benzene rings could be ultimately degraded by microorganisms in acclimated active sludge. Electrospray ionization-mass spectroscopy (ESI-MS) analysis of biodegradation intermediates indicate that stepwise omega, beta-oxidation of EO chains or fission of EO chains, and further omega, beta-oxidation of alkyl-chain for short-EO-chain NPEOs constitute the main pathway in the early stage, and complete biodegradation occur when the benzene rings in these molecules are opened in the later stage.