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Nerve injury induced microglia activation, which released inflammatory mediators and developed neuropathic pain. Picroside Ⅱ (PⅡ) attenuated neuropathic pain by inhibiting the neuroinflammation of the spinal dorsal horn; however, how it engaged in the cross talk between microglia and neurons remained ambiguous. This study aimed to investigate PⅡ in the modulation of spinal synaptic transmission mechanisms on pain hypersensitivity in neuropathic rats. We investigated the analgesia of PⅡ in mechanical and thermal hyperalgesia using the spinal nerve ligation (SNL)-induced neuropathic pain model and formalin-induced tonic pain model, respectively. RNA sequencing and network pharmacology were employed to screen core targets and signaling pathways. Immunofluorescence staining and qPCR were performed to explore the expression level of microglia and inflammatory mediator mRNA. The whole-cell patch–clamp recordings were utilized to record miniature excitatory postsynaptic currents in excitatory synaptic transmission. Our results demonstrated that the analgesic of PⅡ was significant in both pain models, and the underlying mechanism may involve inflammatory signaling pathways. PⅡ reversed the SNL-induced overexpression of microglia and inflammatory factors. Moreover, PⅡ dose dependently inhibited excessive glutamate transmission. Thus, this study suggested that PⅡ attenuated neuropathic pain by inhibiting excitatory glutamate transmission of spinal synapses, induced by an inflammatory response on microglia. [ABSTRACT FROM AUTHOR]

Abstract Background Data on effect of regular liver function monitoring during anti-TB treatment is limited in China. This study aimed to evaluate the effects of scheduled liver function monitoring on identification of asymptomatic liver damage and anti-TB treatment outcomes during anti-TB treatment. Methods A retrospective analysis was performed based on a national-level cohort study. A total of 273 patients developing liver dysfunction were divided into two groups, 111 patients who were diagnosed through scheduled liver function test within two months after initiation of anti-TB treatment formed scheduled monitoring group, others who were diagnosed due to developing symptoms formed passive detection group (n = 162). The two groups were compared through clinical features, prognosis of liver dysfunction and impact on anti-TB treatment using propensity score weighting analysis. Results 33.3% of 273 patients did not have any clinical symptoms, including 8 with severe hepatotoxicity. 1.8% in scheduled monitoring group and 11.1% in passive detection group required hospitalization (P = 0.004). Regarding the prognosis of liver dysfunction, most patients recovered, no death happened in scheduled monitoring group while 3 died in passive detection group. In terms of impact on anti-TB treatment, 35.1% in scheduled monitoring group and 56.8% in passive detection group changed their anti-TB treatment (P = 0.001). Conclusions Scheduled monitoring is effective in identifying asymptomatic liver damage, reducing hospitalization rate and improving compliance of anti-TB treatment.

Although fluoroquinolones (FQs) are the backbone drugs for the treatment of multidrug-resistant tuberculosis (MDR-TB), the knowledge about the resistance pattern and molecular characterization of new-generation FQs in Chongqing is limited. This study aimed to investigate the resistance rate and mutation types of later-generation FQs against MDR-TB in Chongqing, and further to explore the relationship between different genotypes and phenotypes. A total of 967 clinical strains were characterized using multilocus sequence typing and drug susceptibility testing, followed by analysis of genotype/phenotype association. The 229 (23.7%, 229/967) isolates were identified as MDR-TB. The most effective agent against MDR-TB was gatifloxacin (GFX) (20.1%, 46/229), and the highest resistant rate was observed in ofloxacin (OFX) (41.0%, 94/229). Of the 190 strains (83.0%) identified as Beijing genotype, 111 isolates were modern Beijing genotype (58.4%) and 79 isolates were ancient Beijing genotype (41.6%). By analyzing 94 OFX-resistant isolates, 13 isolates were clustered with the cumulative clustering rate of 13.8% (13/94). Of the 91 isolates (39.7%, 91/229) with a mutation in gyrA gene, mutation in codon 94 was the most prevalent. Only 15 isolates (6.6%, 15/229) harbored a mutation in gyrB gene. There was no significant difference in the mutation rate of gyrA gene between Beijing and non-Beijing genotype, clustered isolates, and nonclustered isolates (p > 0.05). [ABSTRACT FROM AUTHOR]

JOURNAL/nrgr/04.03/01300535-202501000-00032/figure1/v/2024-05-14T021156Z/r/image-tiff Human brain development is a complex process, and animal models often have significant limitations. To address this, researchers have developed pluripotent stem cell-derived three-dimensional structures, known as brain-like organoids, to more accurately model early human brain development and disease. To enable more consistent and intuitive reproduction of early brain development, in this study, we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture. This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation, resulting in a new type of human brain organoid system. This cerebral organoid system replicated the temporospatial characteristics of early human brain development, including neuroepithelium derivation, neural progenitor cell production and maintenance, neuron differentiation and migration, and cortical layer patterning and formation, providing more consistent and reproducible organoids for developmental modeling and toxicology testing. As a proof of concept, we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins. Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns, including bursts of cortical cell death and premature differentiation. Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity, accompanied by compensatory cell proliferation at ectopic locations. The convenience, flexibility, and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental, neurological, and neurotoxicological studies., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)