The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-37 (Interleukin 37), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. To address the function of IL-37 in NSCLC, we first evaluated IL-37 expression in the human NSCLC tissues; then the IL-37 function was assessed in vitro and in vivo in a xenografted lung tumor model. IL-37 was barely expressed in the NSCLC tissue but highly expressed in the adjacent normal tissue. This expression profile was validated by ELISA (Enzyme-linked immunoassay), western blot and immunohistochemical staining. Recombinant IL-37 could suppress cell migration, invasion and proliferation and promote cell apoptosis in NSCLC cell line A549 and SK-MES-1. IL-37 inhibited the IL-6/STAT3 pathway and also the downstream targets Bcl-2, NEDD9 and Cyclin D1. Overexpressing IL-6 or constitutive active STAT3 eliminated the anti-tumor effects of IL-37. Furthermore, IL-37 expression in vivo could inhibit the cancer development. Our results showed that IL-37 plays an inhibitory role in lung cancer development, possibly through IL-6/STAT3 pathway.

• MeSH
• interleukin-1 genetika   metabolismus   MeSH
• lidé MeSH
• mediátory zánětu metabolismus   MeSH
• nádorová transformace buněk imunologie   MeSH
• nemalobuněčný karcinom plic * genetika   metabolismus   patologie   MeSH
• receptory interleukinu-6 antagonisté a inhibitory   genetika   metabolismus   MeSH
• signální transdukce MeSH
• transkripční faktor STAT3 antagonisté a inhibitory   genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

The incidence of obesity in the population is gradually increasing. Obesity can cause a variety of complications in the digestive system such as gastroesophageal reflux disease, and impacts the integrity of the esophageal mucosal barrier and esophageal motility. However, not many studies have focused on the effect of varying degrees of obesity on the esophagus. A total of 611 participants were included in this study. We divided them into three groups according to their body mass index (BMI): the normal weight group, the overweight group, and the obesity group. We performed a retrospective comparison between groups based on indicators from high resolution esophageal manometry (HREM) and 24-hour pH impedance monitoring, and did a correlation analysis on multiple indicators such as esophageal mucosal barrier, esophageal motility, and acid reflux. The mean nocturnal baseline impedance (MNBI) in the overweight and obesity groups was lower than that in the normal group. The MNBI of the subjects in Z5-Z6 channels in the overweight group was significantly lower than that in the normal group. With respect to Z3-Z6 channels, MNBI values in the obesity group were significantly lower than those in the normal group. 'The acid exposure time (AET), the DeMeester scores (DMS) and 24-hour total reflux episodes was significantly higher in the obesity group than those in the normal and overweight groups. The upper esophageal sphincter (UES) residual pressure, and intrabolus pressure (IBP) in the overweight and obesity groups were significantly higher than those in the normal group. In addition, lower esophageal sphincter (LES) resting pressure, and esophagogastric junction contractile integral (EGJ-CI) in the obesity group were significantly higher than those in the normal group. We found that increase in body weight affected the integrity of esophageal mucosa, and different degrees of increase associated with different degrees and different aspects of changes in esophageal motility.

• MeSH
• gastroezofageální reflux * diagnóza   MeSH
• lidé MeSH
• nadváha * MeSH
• obezita diagnóza   komplikace   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Noncompaction cardiomyopathy is characterized by the presence of extensive trabeculations, which could lead to heart failure and malignant arrhythmias. How trabeculations resolve to form compact myocardium is poorly understood. Elucidation of this process is critical to understanding the pathophysiology of noncompaction disease. Here we use genetic lineage tracing to mark the Nppa+or Hey2+cardiomyocytes as trabecular and compact components of the ventricular wall. We find that Nppa+and Hey2+cardiomyocytes, respectively, from the endocardial and epicardial zones of the ventricular wall postnatally. Interposed between these two postnatal layers is a hybrid zone, which is composed of cells derived from both the Nppa+and Hey2+populations. Inhibition of the fetal Hey2+cell contribution to the hybrid zone results in persistence of excessive trabeculations in postnatal heart. Our findings indicate that the expansion of Hey2+fetal compact component, and its contribution to the hybrid myocardial zone, are essential for normal formation of the ventricular walls.Fetal trabecular muscles in the heart undergo a poorly described morphogenetic process that results into a solidified compact myocardium after birth. Tian et al. show that cardiomyocytes in the fetal compact layer also contribute to this process, forming a hybrid myocardial zone that is composed of cells derived from both trabecular and compact layers.

• MeSH
• buněčný rodokmen MeSH
• kardiomyocyty metabolismus   MeSH
• kardiomyopatie vrozené   embryologie   metabolismus   MeSH
• myokard metabolismus   patologie   MeSH
• myši MeSH
• natriuretický peptid typu C metabolismus   MeSH
• novorozená zvířata MeSH
• organogeneze MeSH
• proteinové prekurzory metabolismus   MeSH
• represorové proteiny metabolismus   MeSH
• srdce embryologie   růst a vývoj   MeSH
• srdeční komory embryologie   růst a vývoj   metabolismus   patologie   MeSH
• transkripční faktory bHLH metabolismus   MeSH
• vrozené srdeční vady embryologie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Patients with Alzheimer's disease (AD) related dementia and mild cognitive impairment experience difficulties with spatial navigation (SN). However, SN has rarely been investigated in individuals with subjective cognitive decline (SCD), a preclinical stage with elevated progression rate to symptomatic AD. In this study, 30 SCD subjects and 30 controls underwent cognitive scale (CS) evaluation, a 2D computerized SN test, and resting-state functional magnetic resonance imaging scanning. Two SN brain networks (ego-network and allo-network), each with 10 selected spherical regions, were defined. We calculated the average network functional connectivity (FC) and region-to-region FC within the two networks and evaluated correlations with SN performance. Compared with the controls, the SCD group performed worse in the SN test and showed decreased FC between the right retrosplenial and right prefrontal cortices in the ego-network, and between the right retrosplenial cortex and right hippocampus in the allo-network. The logistic regression model based on SN and FC measures revealed a high area under the curve of .880 in differentiating SCD individuals from controls. These results suggest that SN network disconnection contributes to spatial deficits in SCD, and SN and FC measures could benefit the preclinical detection of subjects with incipient AD dementia.

• MeSH
• Alzheimerova nemoc * diagnostické zobrazování   MeSH
• ego MeSH
• kognitivní dysfunkce * diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek MeSH
• zmatenost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This study was to evaluate the efficacy of TOXO-XL (XL), an integrated mycotoxin-mitigating agent, on aflatoxin B1 (AFB1)-induced damage in Leghorn male hepatoma (LMH), porcine jejunum epithelial cell line (IPEC-J2) and porcine alveolar macrophages (3D4/21) cells, and to explore its potential mechanisms. The results showed that 30% inhibition concentration (IC30) of AFB1 in LMH, IPEC-J2 and 3D4/21 cells was 0.5, 15.0, and 2.5 mg/L, respectively. Notably, cell viability, ROS, apoptosis and DNA lesion induced by AFB1 (IC30) could be ameliorated by the supplementation with XL at the dosage of 0.025, 0.025 and 0.005%, respectively. Additionally, the migration and phagocytosis abilities impaired by AFB1 were also restored by XL in 3D4/21. Further experiments revealed that XL supplementation markedly attenuated AFB1-induced inflammatory response by decreasing IL-1β, IL-6 and IL-10 in LMH, IL-6 in IPEC-J2 and IL-1β in 3D4/21 cells. Meanwhile, XL supplementation reversed the alterations of BAX, BCL-2 and caspase-3 induced by AFB1 in the three cells, suggesting that AFB1-induced apoptosis may be suppressed via the mitochondria-dependent pathway. Furthermore, XL may have a protective effect on the intestinal barrier through the restoration of occludin protein. Conclusively, these findings indicated that XL could alleviate AFB1-induced cytotoxicity in the three cells, potentially through the regulation of cytokines, ROS, apoptotic and DNA damage signaling.

• MeSH
• aflatoxin B1 toxicita   metabolismus   MeSH
• apoptóza MeSH
• epitelové buňky MeSH
• hepatocelulární karcinom * metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• kur domácí metabolismus   MeSH
• nádory jater * metabolismus   MeSH
• prasata MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• tisková chyba MeSH

Tumors can reprogram the functions of metabolic enzymes to fuel malignant growth; however, beyond their conventional functions, key metabolic enzymes have not been found to directly govern cell mitosis. Here, we report that glutamine synthetase (GS) promotes cell proliferation by licensing mitotic progression independently of its metabolic function. GS depletion, but not impairment of its enzymatic activity, results in mitotic arrest and multinucleation across multiple lung and liver cancer cell lines, patient-derived organoids and xenografted tumors. Mechanistically, GS directly interacts with the nuclear pore protein NUP88 to prevent its binding to CDC20. Such interaction licenses activation of the CDC20-mediated anaphase-promoting complex or cyclosome to ensure proper metaphase-to-anaphase transition. In addition, GS is overexpressed in human non-small cell lung cancer and its depletion reduces tumor growth in mice and increases the efficacy of microtubule-targeted chemotherapy. Our findings highlight a moonlighting function of GS in governing mitosis and illustrate how an essential metabolic enzyme promotes cell proliferation and tumor development, beyond its main metabolic function.

• MeSH
• glutaminsynthetasa MeSH
• licence MeSH
• lidé MeSH
• myši MeSH
• nádory plic * MeSH
• nemalobuněčný karcinom plic * MeSH
• proliferace buněk MeSH
• proteiny buněčného cyklu metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Resistance to glucocorticoids (GC), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-offunction experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GC-resistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GC against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

• MeSH
• antigeny CD9 * metabolismus   genetika   MeSH
• chemorezistence * genetika   MeSH
• dexamethason farmakologie   MeSH
• dítě MeSH
• glukokortikoidy * farmakologie   terapeutické užití   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• pre-B-buněčná leukemie * farmakoterapie   metabolismus   genetika   patologie   MeSH
• předškolní dítě MeSH
• receptory glukokortikoidů metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Human Reproductive and Prenatal Genetics covers the field of human reproductive and prenatal genetics and presents the latest material from a detailed molecular, cellular and translational perspective. This book aims to be among the largest and most useful references available. Considering its timeliness and potential international impact, this all-inclusive and authoritative work is ideal for researchers, students, and clinicians worldwide.

• MeSH
• asistovaná reprodukce MeSH
• gametogeneze genetika   MeSH
• infertilita MeSH
• pohlavní orgány embryologie   MeSH
• preimplantační diagnóza metody   MeSH
• Publikační typ
• příručky MeSH

• Konspekt
• Obecná genetika. Obecná cytogenetika. Evoluce
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• reprodukční lékařství
• molekulární biologie, molekulární medicína
• embryologie a teratologie
• NLK Publikační typ
• kolektivní monografie

• MeSH
• alkaloidy biosyntéza   MeSH
• Bacteria genetika   metabolismus   MeSH
• biosyntéza peptidů nezávislá na nukleových kyselinách MeSH
• databáze genetické MeSH
• genetické markery MeSH
• houby genetika   metabolismus   MeSH
• metagenom MeSH
• mezinárodní spolupráce MeSH
• multigenová rodina * MeSH
• peptidy metabolismus   MeSH
• polyketidy metabolismus   MeSH
• polysacharidy biosyntéza   MeSH
• proteosyntéza * MeSH
• rostliny genetika   metabolismus   MeSH
• terminologie jako téma MeSH
• terpeny metabolismus   MeSH
• výpočetní biologie normy   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH