Abstract Autophagy is a major means for the elimination of protein inclusions in neurons in neurodegenerative diseases such as Parkinson’s disease (PD). Yet, the mechanism of autophagy in the other brain cell type, glia, is less well characterized and remains largely unknown. Here we present evidence that the PD risk factor Cyclin G-associated kinase (GAK)/dAuxilin (dAux) is a new component in glial autophagy. GAK/dAux directly interacts with ULK1/Atg1 via its uncoating domain. Lack of GAK/dAux increases the autophagosome number and size in adult fly glia and mouse microglia, and generally upregulates levels of components in the initiation and PI3K class III complexes including ULK1/Atg1, demonstrating that GAK/dAux regulates the onset of glial autophagy. Consistently, lack of GAK/dAux enhances Atg1 and Atg9 trafficking to autophagosomes, promoting autophagy initiation. On the other hand, lack of GAK/dAux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/dAux might play additional roles in glial autophagy. Our findings identify a new autophagy factor in glia; considering the pivotal role of glia under pathological conditions, targeting glial autophagy is potentially a therapeutic strategy for PD.
Gout is a common inflammatory arthritis, which is mainly caused by the deposition of monosodium urate (MSU) in tissues. Transcriptomics was used to explore the pathogenesis and treatment of gout in our work.
Human papillomavirus (HPV) infection is one of the main causes of esophageal carcinoma (ESCA), and its carcinogenic mechanisms in ESCA require further investigation. E6 and E7 are HPV oncogenes, and their genomic integration is a crucial reason for the transformation of host cells into cancer cells. In order to reveal the role of oncogenes E6 and E7 in ESCA cells, the RNA-Seq raw data for HPV18-positive and -negative esophageal squamous cell carcinoma (ESCC) samples derived from the NCBI BioProject database were analyzed, and the differentially expressed genes were identified. Moreover, differentially expressed genes were enriched significantly in multiple cell death pathways, including apoptosis (cyclin-dependent kinase inhibitor 2A, plakophilin 1 and desmoglein 3), pyroptosis (gasdermin A, gasdermin C, NLR family pyrin domain containing 3, absent in melanoma 2, NLR family pyrin domain containing 1 and Toll like receptor 1) and autophagy (Unc-51 like autophagy activating kinase 1, adrenoceptor beta 2). Consequently, the effects of cisplatin-induced apoptosis and Hank's balanced salt solution-induced autophagy, and α-ketoglutarate-induced pyroptosis in the ESCC-expressing E6 and E7 cells were verified. Therefore, the expression of E6E7 may culminate in the inhibition of multiple cell death modes, which may also be one of the mechanisms of oncogene-induced carcinogenesis.
The antlion species Myrmeleon trigonois Bao & Wang, 2006 is endemic to Chinese mainland; it has pronotum with a pair of pale yellow spots, and modified ectoproct, forming a hook-like projection posteroventrally. Based on morphological comparison and molecular evidence, we found that all paratypes of M. trigonois represent a different species than its holotype. Here, Myrmeleon shalulianus Zheng & Liu, sp. nov., is described to accommodate all paratypes of M. trigonois and a series of newly supplemented specimens from Yunnan (China). The distribution pattern of these two species is clarified. Larvae of both M. trigonois and M. shalulianus sp. nov. are described and compared. Furthermore, the bee fly parasitoid (Diptera: Bombyliidae) of the genus Taiwanon Evenhuis, 2018 was reared from the immature stages of M. trigonois in an artificial environment. Taiwanon is newly recorded from the Chinese mainland.
Oncogene E6 plays a critical role in the development and progression of esophageal cancer caused by human papillomavirus (HPV) infection. Alpha‐ketoglutarate (AKG) is a key metabolite in the tricarboxylic acid cycle and has been widely used as a dietary and anti‐ageing supplement. In this study, we found that treating esophageal squamous carcinoma cells with a high dose of AKG can induce cell pyroptosis. Furthermore, our research confirms that HPV18 E6 inhibits AKG‐induced pyroptosis of esophageal squamous carcinoma cells by lowering P53 expression. P53 downregulates malate dehydrogenase 1 (MDH1) expression; however, MDH1 downregulates L‐2‐hydroxyglutarate (L‐2HG) expression, which inhibits a rise in reactive oxygen species (ROS) levels—as L‐2HG is responsible for excessive ROS. This study reveals the actuating mechanism behind cell pyroptosis of esophageal squamous carcinoma cells induced by high concentrations of AKG, and we posit the molecular pathway via which the HPV E6 oncoprotein inhibits cell pyroptosis.
Introduction: It is common that personality disorder (PD) co-occurs with major depressive disorder (MDD). In the current literature, there is a dearth of information on the co-occurrence of PD and MDD among Chinese population. Materials and Methods: 609 individuals were randomly sampled from outpatients diagnosed as MDD in Shanghai Mental Health Center. Co-morbidity of PDs was assessed using the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+) and eligible subjects were interviewed with the Structured Clinical Interview for DSM-IV Axis II (SCID-II). The score of PDQ-4+ and the rate of SCID-II PD between subjects diagnosed with MDD and those with anxiety disorders (AD) were compared. Results: Two hundred fifty-eight outpatients (42.36%) with MDD were recognized to possess at least one criterion of diagnosis for PD, according to the DSM-IV. The most prevalent PD was depressive PD (14.61%), followed by avoidant (11.49%) and borderline (11.49%) PD. Cluster C PDs (anxious and panic PD) were the most common PD types (12.12%) when compared to other clusters. Compared to patients with AD, individuals with MDD were significantly more likely to have paranoid PD (6.6% vs. 3.3%, p = 0.011), borderline PD (11.5% vs. 3.7%, p = 0.000), passive-aggressive PD (5.6% vs. 2.4%, p = 0.007), and depressive PD (14.6% vs. 7.8%, p = 0.000). Discussion: The finding indicates that there is a high prevalence of PD among patients with MDD. More significant co-morbidity rates of PDs in MDD have been found when compared with AD. Further studies for the longitudinal impact of the PD-MDD co-morbidity are in need.
Autophagy is a major means for the elimination of protein inclusions in neurons in neurodegenerative diseases such as Parkinson’s disease (PD). Yet, the mechanism of autophagy in the other brain cell type, glia, is less well characterized and remains largely unknown. Here, we present evidence that the PD risk factor, Cyclin-G-associated kinase (GAK)/ Drosophila homolog Auxilin (dAux), is a component in glial autophagy. The lack of GAK/dAux increases the autophagosome number and size in adult fly glia and mouse microglia, and generally up-regulates levels of components in the initiation and PI3K class III complexes. GAK/dAux interacts with the master initiation regulator UNC-51like autophagy activating kinase 1/Atg1 via its uncoating domain and regulates the trafficking of Atg1 and Atg9 to autophagosomes, hence controlling the onset of glial autophagy. On the other hand, lack of GAK/dAux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/dAux might play additional roles. Importantly, dAux contributes to PD-like symptoms including dopaminergic neurodegeneration and locomotor function in flies. Our findings identify an autophagy factor in glia; considering the pivotal role of glia under pathological conditions, targeting glial autophagy is potentially a therapeutic strategy for PD.
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