Autophage

Preeclampsia (PE) is a common pregnancy complication with a high mortality rate. Abnormally activated endoplasmic reticulum stress (ERS) is believed to be responsible for the destruction of key placental cells-trophoblasts. Phenylbutyric acid (4-PBA), an ERS inhibitor, is involved in regulating the development of ERS-related diseases. At present, how 4-PBA affects trophoblasts and its mechanisms is still unclear. In this study, PE cell models were established by stimulating HTR-8/SVneo cells with hypoxia...

Interleukin 17A (IL-17A) is a key cytokine promoting osteoblast formation, which contributes to osteogenesis. IL-17A functions in autophagy inhibition within osteoblasts. Metallothionein-2 (MT-2), as an important reactive oxygen species (ROS)-scavenging molecule, prevents oxidative stress from damaging osteoblast formation. The relationship between IL-17A-regulated autophagy and MT-2 production under oxidative stress deserves further exploration. In this study, we first investigated the roles of IL-17A in osteoblastic differentiation and ROS production in osteoblast precursors in the presence of hydrogen peroxide (H2 O2 )...

Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included...

The compound 6PPD is widely acknowledged for its antioxidative properties; however, concerns regarding its impact on aquatic organisms have spurred comprehensive investigations. In our study, we advanced our comprehension by revealing that exposure to 6PPD could induce cardiac dysfunction, myocardial injury and DNA damage in adult zebrafish. Furthermore, our exploration unveiled that the exposure of cardiomyocytes to 6PPD resulted in apoptosis and mitochondrial injury, as corroborated by analyses using transmission electron microscopy and flow cytometry...

Activation of autophagy, a process of cellular stress response, leads to the breakdown of proteins, organelles, and other parts of the cell in lysosomes, and can be linked to several ailments, such as cancer, neurological diseases, and rare hereditary syndromes. Thus, its regulation is very carefully monitored. Transcriptional and post-translational mechanisms domestically or in whole organisms utilized to control the autophagic activity, have been heavily researched. In modern times, microRNAs (miRNAs) are being considered to have a part in post-translational orchestration of the autophagic activity, with miR-21 as one of the best studied miRNAs, it is often more than expressed in cancer cells...

BACKGROUND: p66Shc, as a redox enzyme, regulates reactive oxygen species (ROS) production in mitochondria and autophagy. However, the mechanisms by which p66Shc affects autophagosome formation are not fully understood. METHODS: p66Shc expression and its location in the trophoblast cells were detected in vivo and in vitro. Small hairpin RNAs or CRISPR/Cas9, RNA sequencing, and confocal laser scanning microscope were used to clarify p66Shc's role in regulating autophagic flux and STING activation...

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is a frequently used herbal medicine worldwide, and is used to treat cough, hepatitis, cancer and influenza in clinical practice of traditional Chinese medicine. Modern pharmacological studies indicate that prenylated flavonoids play an important role in the anti-tumor activity of licorice, especially the tumors in stomach, lung, colon and liver. Wighteone is one of the main prenylated flavonoids in licorice, and its possible effect and target against colorectal cancer have not been investigated...

Intracerebral hemorrhage (ICH), for which there are currently no effective preventive or treatment methods, has a very high fatality rate. Statins, such as atorvastatin (ATV), are the first-line drugs for regulating blood lipids and treating hyperlipidemia-related cardiovascular diseases. However, ATV-associated ICH has been reported, although its incidence is rare. In this study, we aimed to investigate the protective action and mechanisms of berberine (BBR) against ATV-induced brain hemorrhage. We established an ICH model in zebrafish induced by ATV (2 μM) and demonstrated the effects of BBR (10, 50, and 100 μM) on ICH via protecting the vascular network using hemocyte staining and three transgenic zebrafish...

BACKGROUND: Helsmoortel-Van der Aa syndrome is a neurodevelopmental disorder in which patients present with autism, intellectual disability, and frequent extra-neurological features such as feeding and gastrointestinal problems, visual impairments, and cardiac abnormalities. All patients exhibit heterozygous de novo nonsense or frameshift stop mutations in the Activity-Dependent Neuroprotective Protein (ADNP) gene, accounting for a prevalence of 0.2% of all autism cases worldwide. ADNP fulfills an essential chromatin remodeling function during brain development...

Proteins are known to perform an astonishing array of functions thanks to their ability to cooperate and modulate each other's properties. Inside cells, proteins can assemble into large multi-subunit complexes to carry out complex cellular functions. The correct assembly and maintenance of the functional state of macromolecular protein complexes is crucial for human health. Failure to do so leads to loss of function and potential accumulation of harmful materials, which is associated with a variety of human diseases such as neurodegeneration and cancer...

Lead is a widespread environmental pollutant with serious adverse effects on human health, but the mechanism underlying its toxicity remains elusive. This study aimed to investigate the role of miR-584-5p / Ykt6 axis in the toxic effect of lead on HK-2 cells and the related mechanism. Our data suggested that lead exposure caused significant cytotoxicity, DNA and chromosome damage to HK-2 cells. Mechanistically, lead exposure down-regulated miR-584-5p and up-regulated Ykt6 expression, consequently, autophagosomal number and autophagic flux increased, lysosomal number and activity decreased, exosomal secretion increased...

Heme oxygenase HO-1 (HMOX) regulates cellular inflammation and apoptosis, but its role in regulation of autophagy in Mycoplasma bovis infection is unknown. The objective was to determine how the HO-1/CO- Protein kinase RNA-like endoplasmic reticulum kinase (PERK)-Ca2+ - transcription factor EB (TFEB) signaling axis induces autophagy and regulates clearance of M. bovis by bovine mammary epithelial cells (bMECs). M. bovis inhibited autophagy and lysosomal biogenesis in bMECs and suppressed HO-1 protein and expression of related proteins, namely nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (keap1)...

Colon cancer remains a clinical challenge in industrialised countries. Its treatment with 5-Flurouracil (5-FU) develops many side effects and resistance. Thus, several strategies have been undertaken so far, including the use of drug cocktails and polypharmacology. Heme oxygenase-1 (HO-1) is an emerging molecular target in the treatment of various cancers. We recently demonstrated that a combination of HO-1 inhibitors with 5-FU and the corresponding hybrids SI1/17, SI1/20, and SI1/22, possessed anticancer activity against prostate and lung cancer cells...

Macroautophagy (referred to as autophagy hereafter) is a highly conserved catabolic process which sequesters intracellular substrates for lysosomal degradation. Autophagy-related proteins have been shown to be involved in various aspects of tumor development by engaging with multiple cellular substrates. We recently uncovered a novel role for autophagy in regulating the signaling and levels of PDGFRA, a receptor tyrosine kinase amplified in several cancers. We discovered that PDGFRA can be targeted to autophagic degradation by binding the autophagy cargo receptor SQSTM1...

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses...

ETHNOPHARMACOLOGICAL RELEVANCE: Rosmarinic acid (RA), a natural polyphenol abundant in numerous herbal remedies, has been attracting growing interest owing to its exceptional ability to protect the liver. Toosendanin (TSN), a prominent bioactive compound derived from Melia toosendan Siebold & Zucc., boasts diverse pharmacological properties. Nevertheless, TSN possesses remarkable hepatotoxicity. Intriguingly, the potential of RA to counteract TSN-induced liver damage and its probable mechanisms remain unexplored...

Cadmium, an environmental toxicant, severely impairs male reproductive functions and currently lacks effective clinical treatments. Mesenchymal stem cell-derived exosomes (MSC-Exos) are increasingly recognized as a potential alternative to whole-cell therapy for tissue injury and regeneration. This study aims to investigate the protective effects of MSC-Exos against cadmium toxicity on male reproduction. Our findings reveal that MSC-Exos treatment significantly promotes spermatogenesis, improves sperm quality, and reduces germ cell apoptosis in cadmium-exposed mice...

Autophagy, a catabolic process integral to cellular homeostasis, is constitutively active under physiological and stress conditions. The role of autophagy as a cellular defense response becomes particularly evident upon exposure to nanomaterials (NMs), especially environmental nanoparticles (NPs) and nanoplastics (nPs). This has positioned autophagy modulation at the forefront of nanotechnology-based therapeutic interventions. While NMs can exploit autophagy to enhance therapeutic outcomes, they can also trigger it as a pro-survival response against NP-induced toxicity...

BACKGROUND: Liver cancer has a high incidence and mortality rate worldwide, and there is an urgent need to identify new therapeutic strategies and predictive targets to improve the clinical outcomes of advanced liver cancer. Ferroptosis holds promise as a novel strategy for cancer therapy. Epigenetic dysregulation is a hallmark of cancer, and noncoding RNAs are tightly involved in cell fate determination. Therefore, we aimed to identify a novel ferroptosis regulator from aberrantly expressed microRNAs that may serve as a novel biomarker and therapeutic target for liver cancer...

Renin-angiotensin system activation contributes to skeletal muscle atrophy in aging individuals with chronic diseases. We aimed to explore the effects of cholecalciferol (VD3 ) and calcitriol (1,25VD3 ) on signaling of muscle proteolysis and oxidative stress in myotubes challenged with angiotensin II (AII). The mouse C2C12 myotubes were assigned to vehicle, AII, AII + VD3 , AII + 1,25VD3 , and AII + losartan groups. The expression levels of muscle-specific E3 ubiquitin ligase proteins, autophagy-related proteins, and oxidative stress markers were investigated...