LC3B-regulated autophagy mitigates zinc oxide nanoparticle-induced epithelial cell dysfunction and acute lung injury.

Zinc oxide nanoparticles (ZnONPs) are widely utilized across various industries, raising concerns about their potential toxicity, especially in the respiratory system. This study explores the role of autophagy, regulated by microtubule-associated protein 1A/1B-light chain 3B (LC3B), in ZnONPs-induced toxicity using both in vivo (LC3B knockout mice) and in vitro (BEAS-2B cells) models. Our findings demonstrate that LC3B-regulated autophagy mitigates ZnONPs-induced epithelial cell dysfunction and acute lung injury.

N6-methyladenosine demethylase FTO regulates neuronal oxidative stress via YTHDC1-ATF3 axis in arsenic-induced cognitive dysfunction.

Excessive exposure to metals in daily life has been proposed as an environmental risk factor for neurological disorders. Oxidative stress is an inevitable stage involved in the neurotoxic effects induced by metals, nevertheless, the underlying mechanisms are still unclear. In this study, we used arsenic as a representative environmental heavy metal to induce neuronal oxidative stress and demonstrated that both in vitro and in vivo exposure to arsenic significantly increased the level of N6-methyladenosine (m6A) by down-regulating its demethylase FTO.

Recommendations for the selection of nucleoside analogues as antihuman herpesvirus drugs: a real-world analysis of reported cases from the FDA adverse event reporting system.

Objective: The aim of this study is to provide guidance for refining medication protocols, developing alternative strategies, and enhancing protection against herpesvirus infections in personalized clinical settings.

Methods: Adverse drug events (ADEs) data for anti-herpesvirus from the first quarter of 2004 to the fourth quarter of 2022 were collected from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis was performed using Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN) methods for data mining.

SUMOylation modification of FTO facilitates oxidative damage response of arsenic by IGF2BP3 in an m6A-dependent manner.

N6-methyladenosine (m6A) is the most common form of internal post-transcriptional methylation observed in eukaryotic mRNAs. The abnormally increased level of m6A within the cells can be catalyzed by specific demethylase fat mass and obesity-associated protein (FTO) and stay in a dynamic and reversible state. However, whether and how FTO regulates oxidative damage via m6A modification remain largely unclear.

NBR1-mediated autophagic degradation of caspase 8 protects vascular endothelial cells against arsenite-induced apoptotic cell death.

Vascular endothelial cells play a critical role in maintaining the health of blood vessels, but dysfunction can lead to cardiovascular diseases. The impact of arsenite exposure on cardiovascular health is a significant concern due to its potential adverse effects. This study aims to explore how NBR1-mediated autophagy in vascular endothelial cells can protect against oxidative stress and apoptosis induced by arsenite.

TBC1D23 mediates Golgi-specific LKB1 signaling.

Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive.

Disruption of the lung-gut-brain axis is responsible for cortex damage induced by pulmonary exposure to zinc oxide nanoparticles.

Increasing evidence shows that gut microbiota is important for host health in response to metal nanomaterials exposure. However, the effect of gut microbiota on the cortex damage caused by pulmonary exposure to zinc oxide nanoparticles (ZnONPs) remains mainly unknown. In this study, a total of 48 adult C57BL/6J mice were intratracheally instilled with 0.

Heterozygous disruption of beclin 1 alleviates neurotoxicity induced by sub-chronic exposure of arsenite in mice.

Arsenite is a well-documented neurotoxicant that widely exists in the environment. However, the detailed mechanisms of arsenite neurotoxicity are not fully clarified. Autophagy has been reported to be involved in many neurological problems induced by arsenite.

Inhibition of cGAS ameliorates acute lung injury triggered by zinc oxide nanoparticles.

Purpose: Zinc oxide nanoparticles (ZnONPs) have been widely used in various industrial and biomedical fields. Occupational or accidental inhalation exposure to ZnONPs might lead to acute lung injury (ALI). Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) are critical for the initiation and expansion of inflammation and contribute to tissue injury; however, the role and mechanism of the cGAS-STING pathway in ALI-induced by ZnONPs are unclear.

Polystyrene nanoparticles enhance the adverse effects of di-(2-ethylhexyl) phthalate on male reproductive system in mice.

Coexposure of nanoplastics (NPs) with other pollutants adsorbed from the surroundings has received extensive attention. Currently, the combined effects of NPs and plasticizers remain unclear. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer that has raised much concern owing to its ubiquitous pollution and endocrine-disrupting potential.

Intestinal Microbiota-derived Propionic Acid Protects against Zinc Oxide Nanoparticle-induced Lung Injury.

With the rapid development of nanotechnology, the risks of accidental and/or occupational exposure to zinc oxide nanoparticles (ZnONPs) are increasing. Inhalation of ZnONPs induces metal fume fever in humans and acute lung injury (ALI) in animal models. Although the intestinal microbiota is considered an important modulator of various diseases, the role and mechanism of intestinal microbiota in the pathology of ZnONP-induced ALI are unclear.

Prenatal exposure to titanium dioxide nanoparticles induces persistent neurobehavioral impairments in maternal mice that is associated with microbiota-gut-brain axis.

Gestational exposure to titanium dioxide nanoparticles (TiONPs) has been widely reported to have deleterious effects on the brain functions of offspring. However, little attention has been paid to the neurotoxic effects of TiONPs on maternal body after parturition. The pregnant mice were orally administrated with TiONPs at 150 mg/kg from gestational day 8-21.

Ammonium tetrathiomolybdate triggers autophagy-dependent NRF2 activation in vascular endothelial cells.

Ammonium tetrathiomolybdate (TTM) is a copper chelator in clinical trials for treatment of Wilson's disease, tumors and other diseases. In the current study, we innovatively discovered that TTM is a novel NRF2 activator and illustrated that autophagy contributed to TTM-induced NRF2 activation. We showed that TTM treatment promoted NRF2 nuclear translocation and upregulated transcription level of NRF2 target genes including HMOX1, GCLM, and SLC7A11 in vascular endothelial cells (HUVECs).

Polystyrene nanoparticles aggravate the adverse effects of di-(2-ethylhexyl) phthalate on different segments of intestine in mice.

Emerging evidence indicates that nanoplastics (NPs) can transport organic pollutants such as di-(2-ethylhexyl) phthalate (DEHP) into organisms and induce adverse health effects. Nevertheless, the toxic effects of NPs combined with DEHP on mammalian intestine are still unclear. In this study, the C57BL6J mice were exposed to polystyrene nanoparticles (PSNPs), DEHP or them both for 30 days to determine their effects on different segments of intestine and the gut microbiota.

Reciprocal regulation of NRF2 by autophagy and ubiquitin-proteasome modulates vascular endothelial injury induced by copper oxide nanoparticles.

NRF2 is the key antioxidant molecule to maintain redox homeostasis, however the intrinsic mechanisms of NRF2 activation in the context of nanoparticles (NPs) exposure remain unclear. In this study, we revealed that copper oxide NPs (CuONPs) exposure activated NRF2 pathway in vascular endothelial cells. NRF2 knockout remarkably aggravated oxidative stress, which were remarkably mitigated by ROS scavenger.

Recombinant ACE2 protein protects against acute lung injury induced by SARS-CoV-2 spike RBD protein.

Background: SARS-CoV-2 infection leads to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Both clinical data and animal experiments suggest that the renin-angiotensin system (RAS) is involved in the pathogenesis of SARS-CoV-2-induced ALI. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2 and a crucial negative regulator of RAS.

An evolving understanding of sorting signals for endosomal retrieval.

Complex mechanisms govern the sorting of membrane (cargo) proteins at endosomes to ensure that protein localization to the post-Golgi endomembrane system is accurately maintained. Endosomal retrieval complexes mediate sorting by recognizing specific motifs and signals in the cytoplasmic domains of cargo proteins transiting through endosomes. In this review, the recent progress in understanding the molecular mechanisms of how the retromer complex, in conjunction with sorting nexin (SNX) proteins, operates in cargo recognition and sorting is discussed.

Repression of autophagy leads to acrosome biogenesis disruption caused by a sub-chronic oral administration of polystyrene nanoparticles.

As a new widespread contaminant, nanoplastics (NPs) pose a potential risk to human health. Nevertheless, the adverse effects of NPs on the male reproductive system are poorly understood. In this study, we aimed to determine the effects of polystyrene nanoplastics (PS-NPs) (50 nm) on sperm quality, with a focus on the acrosome defects.

PINK1/TAX1BP1-directed mitophagy attenuates vascular endothelial injury induced by copper oxide nanoparticles.

Copper oxide nanoparticles (CuONPs) are widely used metal oxide NPs owing to their excellent physical-chemical properties. Circulation translocation of CuONPs after inhalation leads to vascular endothelial injury. Mitochondria, an important regulatory hub for maintaining cell functions, are signaling organelles in responses to NPs-induced injury.

Targeting Endosomal Recycling Pathways by Bacterial and Viral Pathogens.

Endosomes are essential cellular stations where endocytic and secretory trafficking routes converge. Proteins transiting at endosomes can be degraded via lysosome, or recycled to the plasma membrane, trans-Golgi network (TGN), or other cellular destinations. Pathways regulating endosomal recycling are tightly regulated in order to preserve organelle identity, to maintain lipid homeostasis, and to support other essential cellular functions.

Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling.

Endocytosed proteins can be delivered to lysosomes for degradation or recycled to either the trans-Golgi network or the plasma membrane. It remains poorly understood how the recycling versus degradation of cargoes is determined. Here, we show that multiple extracellular stimuli, including starvation, LPS, IL-6, and EGF treatment, can strongly inhibit endocytic recycling of multiple cargoes through the activation of MAPK11/14.

Mechanism of cargo recognition by retromer-linked SNX-BAR proteins.

Endocytic recycling of internalized transmembrane proteins is essential for many important physiological processes. Recent studies have revealed that retromer-related Sorting Nexin family (SNX)-Bin/Amphiphysin/Rvs (BAR) proteins can directly recognize cargoes like cation-independent mannose 6-phosphate receptor (CI-MPR) and Insulin-like growth factor 1 receptor (IGF1R); however, it remains poorly understood how SNX-BARs select specific cargo proteins and whether they recognize additional ligands. Here, we discovered that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) domain of SNX5 or SNX6 and a bipartite motif, termed SNX-BAR-binding motif (SBM), in the cargoes.

Sec62 Suppresses Foot-and-Mouth Disease Virus Proliferation by Promotion of IRE1α-RIG-I Antiviral Signaling.

Foot-and-mouth disease virus (FMDV) is highly infectious and causes a major plague in animal farming. Unfolded protein response is one of the major cellular responses to pathogenic infections, which performs a crucial role in cell survival, apoptosis, and antiviral innate immune response. In this study, we showed that FMDV infection activated two unfolded protein response branches (PERK-eIF2α and ATF6 signaling) in both baby hamster kidney cells (BHK-21) and porcine kidney (PK-15) cells, whereas it suppressed the IRE1α-XBP1 signaling by decreasing IRE1α level.

The Important Role of Lipid Raft-Mediated Attachment in the Infection of Cultured Cells by Coronavirus Infectious Bronchitis Virus Beaudette Strain.

Lipid raft is an important element for the cellular entry of some viruses, including coronavirus infectious bronchitis virus (IBV). However, the exact role of lipid rafts in the cellular membrane during the entry of IBV into host cells is still unknown. In this study, we biochemically fractionated IBV-infected cells via sucrose density gradient centrifugation after depleting plasma membrane cholesterol with methyl-β-cyclodextrin or Mevastatin.