Zinc oxide nanoparticles have biphasic roles on Mycobacterium-induced inflammation by activating autophagy and ferroptosis mechanisms in infected macrophages.

The ability of zinc oxide nanoparticles (ZnONPs) to induce bacteriostasis in Mycobacterium tuberculosis (M. tb) and their roles in regulating the pathogenic activities of immune cells have been reported previously, but the specific mechanisms underlying these regulatory functions remain unclear. This work aimed to determine how ZnONPs play the antibacterial role against M. tb. In vitro activity assays were employed to determine the minimum inhibitory concentrations (MICs) of the ZnONPs against various strains of M. tb (BCG, H37Rv, and clinical susceptible MDR and XDR strains). The ZnONPs had MICs of 0.5-2 mg/L against all tested isolates. In addition, changes in the expression levels of autophagy and ferroptosis-related markers in BCG-infected macrophages exposed to ZnONPs were measured. BCG-infected mice that were administered ZnONPs were used to determine the ZnONPs functions in vivo. ZnONPs decreased the number of bacteria engulfed by the macrophages in a dose-dependent manner, while different doses of ZnONPs also affected inflammation in different directions. Although ZnONPs enhanced the BCG-induced autophagy of macrophages in a dose-dependent manner, only low doses of ZnONPs activated autophagy mechanisms by increasing the levels of pro-inflammatory factors. The ZnONPs also enhanced BCG-induced ferroptosis of macrophages at high doses. Co-administration of a ferroptosis inhibitor with the ZnONPs improved the anti-Mycobacterium activity of ZnONPs in an in vivo mouse model and alleviated acute lung injury caused by ZnONPs. Based on the above findings, we conclude that ZnONPs may act as potential antibacterial agents in future animal and clinical studies.

Unveiling MRI markers for Parkinson's Disease: GABAergic dysfunction and cortical changes.

OBJECTIVE: The study aimed to investigate changes in basal levels of the inhibitory γ-aminobutyric acid (GABA) neurotransmitter in the sensorimotor cortex (SMC) and cortical gyrification in patients with Parkinson's disease (PD), which could further identify potential imaging biomarkers for PD, particularly in patients with early-onset Parkinson's disease (EOPD). METHOD: Fifty patients with PD (EOPD: 10, late-onset Parkinson's disease [LOPD]: 40) and fifty-two age- and gender-matched healthy controls (HC) underwent GABA-edited 1H MRS of the SMC and high-resolution 3D T1-weighted brain imaging. GABA levels and local gyrification index (LGI) were calculated to assess GABAergic and cortical gyrification deficits in PD. RESULT: The Pearson correlation coefficients revealed significant negative associations between eight indicators, including GABA/Cr level and local gyrification index (LGI) of specific cortical regions (precentral, postcentral, entorhinal, superiortemporal, posteriorcingulate, cuneus, and transversetemporal cortex), and the likelihood of Parkinson's disease (r < -0.4, p < 0.001). Additionally, GABA levels were significantly lower in the SMC region of both EOPD and LOPD patients compared to healthy controls (mean ± SD [u.i.]: EOPD=0.081 ± 0.022 vs. Young-HC=0.112 ± 0.021, p = 0.003; LOPD=0.054 ± 0.024 vs. Old-HC=0.099 ± 0.021, p < 0.001). The logistic regression model was established by using multivariate analysis, identifying two statistically significant indicators: GABA/Cr and LGI of the transversetemporal. The combined model exhibited the highest AUC values in both younger and older populations. CONCLUSION: GABAergic dysfunction may play an important role in the pathogenesis of PD patients. Changes in neurotransmitter and morphological may serve as potential markers for the preclinical diagnosis and progression of PD, including EOPD.

Case report: Rare epithelioid hemangioendothelioma occurs in both main bronchus and lung.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor of endothelial origin with low- to intermediate-grade malignant potentials. Since there is no characteristic clinical or biological marker available for PEH, most cases require a surgical lung biopsy for diagnosis. To date, although some patients with PEH reported in the literature were diagnosed through bronchoscopic biopsy, most of the patients still underwent surgical lung biopsy for confirmation. In this case report, we present a rare case diagnosed as PEH through endobronchial biopsies due to the presence of an intraluminal mass that blocked the trachea and caused atelectasis in the right upper lobe. Moreover, since surgery was not appropriate for this patient with unresectable bilateral multiple nodules, we adopted genetic analysis using NGS to provide a guide for personalized treatment. Then, based on the NGS results, the patient was treated with anti-PD-1 mAb and sirolimus for 1 year and has been stable in a 1-year follow-up examination.