Acute lung injury (ALI) is a severe respiratory disease with a high mortality rate. The integrity of the pulmonary endothelial barrier influences the development and prognosis of ALI. Therefore, it has become an important target for ALI treatment.
View Article and Find Full Text PDFThe preservation of female fertility under unfavorable conditions is essential for animal reproduction. Inhibition of the target of rapamycin complex 1 (TORC1) is indispensable for Drosophila young egg chamber maintenance under nutrient starvation. Here, we show that knockdown of RagA results in young egg chamber death independent of TORC1 hyperactivity.
View Article and Find Full Text PDFSheng Wu Gong Cheng Xue Bao
April 2023
The gastrointestinal tract is the largest digestive organ and the largest immune organ and detoxification organ, which is vital to the health of the body. is a classic model organism, and its gut is highly similar to mammalian gut in terms of cell composition and genetic regulation, therefore can be used as a good model for studying gut development. target of rapmaycin complex 1 (TORC1) is a key factor regulating cellular metabolism.
View Article and Find Full Text PDFProgestin resistance is the main obstacle for the conservative therapy to maintain fertility in women with endometrial cancer. Brusatol was identified as an inhibitor of the NRF2 pathway; however, its impact on progestin resistance and the underlying mechanism remains unclear. Here, we found that brusatol sensitized endometrial cancer to progestin by suppressing NRF2-TET1-AKR1C1-mediated progestin metabolism.
View Article and Find Full Text PDFNitric oxide (NO) at a high concentration is an effector to kill pathogens during insect immune responses, it also functions as a second messenger at a low concentration to regulate antimicrobial peptide (AMP) production in insects. calcineurin subunit CanA1 is a ubiquitous serine/threonine protein phosphatase involved in NO-induced AMP production. However, it is unclear how NO regulates AMP expression.
View Article and Find Full Text PDFFK506-binding protein 39kD (FKBP39) localizes in the nucleus and contains multiple functional domains. Structural analysis suggests that FKBP39 might function as a transcriptional factor and control juvenile hormone (JH) activity. Here, we show that FKBP39 expresses at a high level and localizes in the nucleolus of fat body cells during the first two larval stages and early third larval stage.
View Article and Find Full Text PDFMacrocentrus cingulum is a principal endoparasite of Ostrinia furnacalis larvae. M. cingulum larvae repress host immune responses for survival and ingest host nutrients for development until emerging.
View Article and Find Full Text PDFPathogen-induced host immune responses reduce the efficacy of pathogens used to control pests. However, compared to the well-deciphered immunity system of Drosophila melanogaster, the immunity system of agricultural pests is largely unconfirmed through functional analysis. Beginning to unveil mechanisms of transcription regulation of immune genes in the Asian corn borer, Ostrinia furnacalis, we cloned the complementary DNA (cDNA) of a transcription factor Relish by rapid amplification of cDNA ends.
View Article and Find Full Text PDFTarget of Rapamycin Complex 1 (TORC1) is a master regulator that coordinates nutrient status with cell metabolism. The GTPase-activating protein towards Rags complex 1 (GATOR1) inhibits TORC1 activity and protects cells from damage during periods of stress. Here we characterize multiple pathways that regulate the expression of the GATOR1 component Nprl3 in Drosophila.
View Article and Find Full Text PDFTarget of rapamycin complex 1 (TORC1) is a master regulator of cell metabolism, and its dysregulation has been linked to an array of pathologies, including cancer and age-related diseases. Nprl3, a component of GTPase-activating protein towards Rags complex 1 (GATOR1), inhibits TORC1 activity under nutrient scarcity status. The mutant exhibits some metabolic defects due to hyper TORC1 activity in Royal jelly (RJ) is a honeybee-secreted product and plays an essential role in caste differentiation that requires TORC1 activity.
View Article and Find Full Text PDFPurpose: Patients with Klinefelter syndrome (KS) who receive assisted reproductive technology (ART) treatment often experience poor pregnancy rates due to decreased fertilization, cleavage, and implantation rates and even an increased miscarriage rate. Mounting evidence from recent studies has shown that various technological advances and approaches could facilitate the success of ART treatment for KS patients. In this review, we summarize the methods for guiding KS patients during ART and for developing optimal strategies for preserving fertility, improving pregnancy rate and live birth rate, and avoiding the birth of KS infants.
View Article and Find Full Text PDFMost animals use the gastrointestinal (GI) tract to digest food. The movement of the ingested food in the GI tract is essential for nutrient absorption. Disordered GI motility and gastric emptying cause multiple diseases and symptoms.
View Article and Find Full Text PDFAflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined.
View Article and Find Full Text PDFAging (Albany NY)
November 2019
Aging and age-related diseases occur in almost all organisms. Recently, it was discovered that the inhibition of target of rapamycin complex 1 (TORC1), a conserved complex that mediates nutrient status and cell metabolism, can extend an individual's lifespan and inhibit age-related diseases in many model organisms. However, the mechanism whereby TORC1 affects aging remains elusive.
View Article and Find Full Text PDFThe TORC1 regulator GATOR1/SEACIT controls meiotic entry and early meiotic events in yeast. However, how metabolic pathways influence meiotic progression in metazoans remains poorly understood. Here we examine the role of the TORC1 regulators GATOR1 and GATOR2 in the response to meiotic double-stranded breaks (DSB) during oogenesis.
View Article and Find Full Text PDFProgestins has been used widely for endometrial cancer (EC) patients. However, long term use of high dose progestin often lead to progestin resistance. Our previous studies have demonstrated that metformin reversed progestin resistance through the downregulation of the expression of glyoxalase I (GLOI) in type I endometrial cancer.
View Article and Find Full Text PDFGestational diabetemellitus (GDM) is a condition whereby a mother's glucose tolerance is impaired with onset or first recognition during pregnancy which is not either type 1 or type 2 diabetes mellitus. Oxidative stress plays an essential role in diabetes, however, whether it also includes in GDM has not been fully clarified. Therefore, we investigated the changes of oxidative stress biomarkers and their relationship with pregnancy outcomes in patients with GDM.
View Article and Find Full Text PDFPARP12 is a mono-ADP-ribosyltransferase, but its function remains largely unknown. Here, we identified four-and-a-half LIM-only protein 2 (FHL2) as a functional partner of PARP12 through protein affinity purification. Although PARP12 did not mono-ADP-ribosylate FHL2 in vitro and in vivo, PARP12 deficiency decreased the protein level of FHL2 by promoting its ubiquitination and increased the expression level of transforming growth factor beta1 (TGF-β1), which is independent of PARP12 enzymatic activity.
View Article and Find Full Text PDFPathological angiogenesis is driven by uncontrolled growth of endothelial cells (ECs), which could lead to retinopathy, tumor and rheumatoid arthritis, etc. ECs must experience multiple cell division process to grow, and cytokinesis is the final step. The present study shows that PEGylated GNRs (PEG-GNRs) specifically target ECs cytokinesis process which results in high ratio of binucleated cells, and these binucleated ECs lose the ability to proliferate.
View Article and Find Full Text PDFCytokinesis is the last step of cell division and is concluded by the abscission of the intercellular bridge that connects two daughter cells. The tight regulation of cytokinesis completion is essential because cytokinesis failure is associated with various human diseases. Here, we report that iASPP, a member of the apoptosis-stimulating proteins of p53 (ASPP) family, is required for proper cell division.
View Article and Find Full Text PDFAim: To study the effect of discoidin I-like domaincontaining protein 3 (EDIL3) depletion on the proliferation and epithelial-mesenchymal transition (EMT) in human lens epithelial cells (LECs).
Methods: RNA interference was used to inhibit the expression of EDIL3 in human LECs . The morphology of cells was observed using an inverted microscope.
TORC1 regulates metabolism and growth in response to a large array of upstream inputs. The evolutionarily conserved trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation. In humans, the GATOR1 complex has been implicated in a wide array of pathologies including cancer and hereditary forms of epilepsy.
View Article and Find Full Text PDFTORC1 is a master regulator of metabolism in eukaryotes that responds to multiple upstream signaling pathways. The GATOR complex is a newly defined upstream regulator of TORC1 that contains two sub-complexes, GATOR1, which inhibits TORC1 activity in response to amino acid starvation and GATOR2, which opposes the activity of GATOR1. While the GATOR1 complex has been implicated in a wide array of human pathologies including cancer and hereditary forms of epilepsy, the in vivo relevance of the GATOR2 complex remains poorly understood in metazoans.
View Article and Find Full Text PDFAim: To investigate the detailed mechanism of Japanese encephalitis virus (JEV) cell entry.
Materials & Methods: Utilize a siRNA library targeting cellular membrane trafficking genes to identify key molecules that mediate JEV entry into human neuronal cells.
Results: JEV enters human neuronal cells by caveolin-1-mediated endocytosis, which depends on a two-step regulation of actin cytoskeleton remodeling triggered by RhoA and Rac1: RhoA activation promoted the phosphorylation of caveolin-1, and then Rac1 activation facilitated caveolin-associated viral internalization.