Meiling Zhu

Pseudomonas aeruginosa ( P. aeruginosa ) is a major opportunistic pathogen whose diverse virulence strategies, increasing antibiotic resistance, and ability to establish persistent infections continue to compromise the efficacy of conventional antimicrobial therapies. Although traditionally regarded as an extracellular pathogen, P. aeruginosa can also enter and persist within host cells, triggering inflammatory responses and cellular injury while simultaneously modulating host autophagic responses. On the one hand, xenophagy and related autophagic processes recognize and deliver intracellular bacteria for lysosomal degradation. Mitophagy eliminates damaged mitochondria generated during infection and limits the accumulation of mitochondrial danger signals. Meanwhile, autophagy regulates inflammasome activation by controlling the removal of damaged organelles and inflammasome components, thereby shaping inflammatory responses during infection. Collectively, these processes contribute to the protective role of autophagy in host defense against P. aeruginosa infection. On the other hand, P. aeruginosa can interfere with or remodel host autophagy through secreted effector molecules, quorum sensing signals, and infection-induced host signaling pathways, resulting in a functional disconnect between autophagic activation and effective bacterial clearance or other antimicrobial responses. This review summarizes current advances in understanding the interplay between autophagy and P. aeruginosa , highlighting the protective functions of autophagy in host defense, the countermeasures employed by P. aeruginosa to evade autophagic clearance, and the therapeutic implications of these host–pathogen interactions. These insights may support the development of host-directed therapeutic approaches targeting autophagy to improve antibacterial defense against P. aeruginosa .

Introduction: The persistent evolution of SARS-CoV-2 has diminished the efficacy of existing vaccines and antibodies, increasing the risks of reinfection and Long COVID. There is a significant need for the development of convenient, broad-spectrum antiviral agents that target the early stage of viral infection. Traditional Chinese Medicine (TCM) volatile oils, with their diverse components and suitability for nasal delivery, demonstrate potential against respiratory viruses. This study aimed to screen bioactive compounds from TCM volatile oils for their ability to inhibit the interaction between the SARS-CoV-2 spike (S) protein and its host receptor, ACE2. Methods: A virtual screening of 47 structurally diverse TCM volatile compounds was performed to identify potential inhibitors of the Spike-ACE2 interaction. The top candidate, dibutyl phthalate (DBP), was further evaluated using in vitro assays including Spike-mediated membrane fusion and pseudovirus infection. Its mechanism was investigated through ELISA, surface plasmon resonance (SPR), ACE2 enzymatic activity assays, molecular docking. To evaluate its broad-spectrum potential, membrane fusion assays were further performed using spike proteins from the wild-type (WT), Delta, and Omicron XBB.1.5 variants. Critical binding residues were identified through molecular docking and subsequently confirmed by site-directed mutagenesis of the Spike receptor-binding domain (RBD). Results: Virtual screening identified ten potential inhibitors, with dibutyl phthalate (DBP) showing the strongest activity. DBP effectively inhibited S protein-mediated membrane fusion ( IC ₅₀ = 64.53 μM) and pseudovirus infection ( IC ₅₀ = 73.06 μM) with specificity. SPR analysis confirmed that DBP competitively inhibited the binding between the S trimer and ACE2 (increasing the K _D from 8.28 nM to 86.7 nM). Mechanistic studies revealed that DBP disrupts the S-ACE2 interaction by targeting the receptor-binding domain (RBD) without affecting ACE2 enzymatic activity. Furthermore, DBP exhibited broad-spectrum inhibitory activity against membrane fusion mediated by the Delta ( IC ₅₀ = 49.22 μM) and Omicron XBB.1.5 ( IC ₅₀ = 53.70 μM) spike variants. Molecular docking and subsequent site-directed mutagenesis identified Tyr453 and Tyr495 as critical residues for DBP binding and its inhibitory function. Discussion: This study elucidates for the first time that DBP functions as a broad-spectrum RBD inhibitor. It binds to the RBD-ACE2 interface, dependent on conserved residues Tyr453 and Tyr495, and acts primarily through steric hindrance to block the Spike-ACE2 interaction. Notably, DBP shares critical aromatic and ester groups with other active-site inhibitors. Structure-activity relationship analysis of its derivatives revealed that introducing additional hydrogen-bond acceptors significantly enhances inhibitory activity, providing a clear structure optimization strategy. While DBP has known toxicity, its antiviral potential may be harnessed through strategic delivery approaches or SAR-guided optimization to advance its development against SARS-CoV-2 variants.

Depression is a psychiatric disorder which affects many aspects of the social life of patients; however, the molecular biological mechanisms underlying its development are not fully understood. Our research reveals that depression onset is associated with BRD2 LLPS-mediated activation of ATG7 super-enhancers (SEs), and we studied BRD2 liquid-liquid phase separation (LLPS) and super-enhancers in depression using chronic mild stress (CMS)-induced rat models and corticosterone-stimulated PC12 cell models. SEs enrichment, core transcription factor ARID5A and target gene ATG7 were found in the prefrontal cortex of depressed rats by ChIP-seq; through in vitro construction of phase separation droplets, fluorescent bleach recovery experiments (FRAP), and verification of the dual luciferase reporter gene, we found that BRD2 mediates transcription through LLPS, driving ATG7 transcriptional activation; while the BET inhibitor JQ1 reverses abnormal ATG7 activation and alleviates depressive behaviors and saving ferritinophagy in animal models of CMS.Our work is the first to elucidate the “phase separation-SEs-ferritinophagy” axis in depression pathogenesis, offering novel therapeutic strategies targeting epigenetic and phase separation mechanisms. It provides new ideas for the pathogenesis and treatment of depression.

Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the JC‑1 staining experiments shown in Fig. 5F on p. 9, the 'mimic NC' and 'inhibitor' panels appeared to show the same cells, even though the green/red ratio was different comparing between the two data panels. In addition, two further instances of duplicated data panels were identified in Figs. S2 and S3, such that data that were allegedly obtained under different experimental conditions appeared to have been derived from the same original sources. After having asked the authors to explain the errors that had occurred in assembling these figures, they responded to explain that the error in Fig. 5F resulted from the incorrect selection of source images for the channels during the image merging process, whereas the errors in Figs. S2 and S3 occurred due to mistakes made in the naming and management of image files during storage. This led to the unintentional use of incorrect images during the process of figure assembly. Moreover, the authors were able to present to the Editorial Office the original data from the JC‑1 staining experiments belonging to Fig. 5F. The Editor of International Journal of Molecular Medicine has agreed that a corrigendum may be published to account for the errors made in assembling Figs. 5, S2 and S3, and the corrected versions of these figures are shown on the next page. All the authors agree with the publication of this corrigendum, and are thankful to the Editor for giving them the opportunity to present this; moreover, the Editor and the authors apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 61, 2021; DOI: 10.3892/ijmm.2021.4894].

The main characteristics of Parkinson’s disease (PD) are the loss of dopaminergic (DA) neurons and abnormal aggregation of cytosolic proteins. However, the exact pathogenesis of PD remains unclear, with ferroptosis emerging as one of the key factors driven by iron accumulation and lipid peroxidation. Glial cells, including microglia, astrocytes, and oligodendrocytes, serve as supportive cells in the central nervous system (CNS), but their abnormal activation can lead to DA neuron death and ferroptosis. This paper explores the interactions between glial cells and DA neurons, reviews the changes in glial cells during the pathological process of PD, and reports on how glial cells regulate ferroptosis in PD through iron homeostasis and lipid peroxidation. This opens up a new pathway for basic research and therapeutic strategies in Parkinson’s disease.

To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 μL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe²⁺, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (PPPP2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (PP2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (PP2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.

Objective: Current evidence on the association between dietary vitamin E intake and the risk of Parkinson's disease (PD) is limited. The aim of the study was to explore the association of dietary vitamin E intake with PD in the United States among adults over 40 years.Methods: We conducted a cross-sectional study with data collected from National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. A total of the sample of 13,340 participants were included. To identify the different characteristics of the participants, we utilized propensity score matching (PSM) to reduce the effects of selection bias and confounding variables. Weighted univariate and multivariable logistic regression were used to examine the association between dietary vitamin E intake and PD before and after matching. Then, restricted cubic spline (RCS) was used to visually describe the possible non-linear relationships. Finally, we employed the subgroup analysis to further investigate the relationship between dietary vitamin E intake and PD.Results: According to the weighted univariate and multivariable logistic regression analysis, vitamin E intake was inversely associated with the risk of PD before and after matching. The results of RCS analysis revealed no non-linear inverse relationship between vitamin E intake and PD before and after matching. The subgroup analysis showed that age may influence the negative association between vitamin E and PD (P < 0.05 for interaction).Conclusion: Among participants over 40 years of age, vitamin E intake was negatively associated with the risk of PD. Our data may support the supplementation of vitamin E to be used as an intervention strategy for the occurrence of PD.

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder and seriously affects quality of life globally. Moxibustion is widely used to treat neurodegenerative diseases in the clinic and has achieved a beneficial clinical effect. However, strict control and high-quality randomized controlled trials are still lacking. Therefore, this trial aims to evaluate the clinical efficacy and safety of moxibustion in patients with PD and preliminarily explore the underlying mechanism. Methods: This is a randomized, single-blind and placebo-controlled trial design in which 70 eligible participants will be randomly divided into a moxibustion group and a sham moxibustion group. Baihui (DU20) and Sishenchong (EX-HN1) are selected for both groups. The treatment will be performed for 30 min per session, two sessions a week for 8 weeks. The mean change in MDS-UPDRS scores (including MDS-UPDRS II, III subscale scores and total scores) from baseline to the observation points will be the primary outcome. The secondary outcomes will include scores on the Parkinson’s Disease Questionnaire-39 (PDQ-39), Fatigue Severity Scale (FSS), Parkinson Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), and Self-Rating Depression Scale (SDS) as well as the Wexner constipation score. All the above outcomes will be assessed at 4 and 8 weeks. Laboratory blood biochemical analysis and functional magnetic resonance imaging (fMRI) will be conducted at baseline and at the end of treatment to explore the potential mechanisms of moxibustion in regulating PD. Discussion: In conclusion, the results of this trial will reveal whether moxibustion is effective for treating motor and nonmotor symptoms in PD. This trial will also preliminarily explore the underlying mechanism of the regulatory effect of moxibustion in PD, which will contribute to providing a theoretical basis for the treatment of PD. Trial registration: ClinicalTrials.gov ChiCTR2000029745. Registered on 9 August 2021.