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Parkinson’s disease (PD) is characterized by α-synuclein (αSNCA) aggregation in dopaminergic neurons. Gradual accumulation of αSNCA aggregates in substantia nigra (SN) diminishes the normal functioning of soluble αSNCA, leading to a loss of dopamine (DA) neurons. In this study, we developed focused ultrasound-targeted microbubble destruction (UTMD)-mediated PD model that could generate the disease phenotype via αSNCA CNS gene delivery. The formation of neuronal aggregates was analyzed with immunostaining. To evaluate the DA cell loss, we used tyrosine hydroxylase immunostaining and HPLC analysis on DA and its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This loss of DA was associated with a dose-dependent impairment in motor function, as assessed by the rotarod motor assessment. We demonstrate that UTMD-induced SNCA expression initiates αSNCA aggregation and results in a 50% loss of DA in SN. UTMD-related dose-dependent neuronal loss was identified, and it correlates with the degree of impairment of motor function. In comparison to chemical neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated and conventional intracerebral (IC)-injected animal models of PD, the UTMD-mediated αSNCA-based mouse model offers the advantage of mimicking the rapid development of the PD phenotype. The PD models that we created using UTMD also prove valuable in assessing specific aspects of PD pathogenesis and can serve as a useful PD model for the development of new therapeutic strategies.

Trichomonas vaginalis is the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection worldwide. Metronidazole (MTZ) is the mainstay of anti-trichomonal chemotherapy; however, drug resistance has become an increasingly worrying issue. Additionally, the molecular events of MTZ-induced cell death in T. vaginalis remain elusive. To gain insight into the differential expression of genes related to MTZ resistance and cell death, we conducted RNA-sequencing of three paired MTZ-resistant (MTZ-R) and MTZ-sensitive (MTZ-S) T. vaginalis strains treated with or without MTZ. Comparative transcriptomes analysis identified that several putative drug-resistant genes were exclusively upregulated in different MTZ-R strains, such as ATP-binding cassette (ABC) transporters and multidrug resistance pumps. Additionally, several shared upregulated genes among all the MTZ-R transcriptomes were not previously identified in T. vaginalis, such as 5′-nucleotidase surE and Na+-driven multidrug efflux pump, which are a potential stress response protein and a multidrug and toxic compound extrusion (MATE)-like protein, respectively. Functional enrichment analysis revealed that purine and pyrimidine metabolisms were suppressed in MTZ-S parasites upon drug treatment, whereas the endoplasmic reticulum-associated degradation (ERAD) pathway, proteasome, and ubiquitin-mediated proteolysis were strikingly activated, highlighting the novel pathways responsible for drug-induced stress. Our work presents the most detailed analysis of the transcriptional changes and the regulatory networks associated with MTZ resistance and MTZ-induced signaling, providing insights into MTZ resistance and cell death mechanisms in trichomonads.

The three most common sexually transmitted infections (STIs) are Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC) and Trichomonas vaginalis (TV). The prevalence of these STIs in Taiwan remains largely unknown and the risk of STI acquisition affected by the vaginal microbiota is also elusive. In this study, a total of 327 vaginal swabs collected from women with vaginitis were analyzed to determine the presence of STIs and the associated microorganisms by using the BD Max CT/GC/TV molecular assay, microbial cultures, and 16S rRNA sequencing. The prevalence of CT, TV, and GC was 10.8%, 2.2% and 0.6%, respectively. A culture-dependent method identified that Escherichia coli and Streptococcus agalactiae (GBS) were more likely to be associated with CT and TV infections. In CT-positive patients, the vaginal microbiota was dominated by L. iners, and the relative abundance of Gardnerella vaginalis (12.46%) was also higher than that in TV-positive patients and the non-STIs group. However, Lactobacillus spp. was significantly lower in TV-positive patients, while GBS (10.11%), Prevotella bivia (6.19%), Sneathia sanguinegens (12.75%), and Gemella asaccharolytica (5.31%) were significantly enriched. Using an in vitro co-culture assay, we demonstrated that the growth of L. iners was suppressed in the initial interaction with TV, but it may adapt and survive after longer exposure to TV. Additionally, it is noteworthy that TV was able to promote GBS growth. Our study highlights the vaginal microbiota composition associated with the common STIs and the crosstalk between TV and the associated bacteria, paving the way for future development of health interventions targeting the specific vaginal bacterial taxa to reduce the risk of common STIs.