Human adipose tissue-derived stem cell extracellular vesicles attenuate ocular hypertension-induced retinal ganglion cell damage by inhibiting microglia- TLR4/MAPK/NF-κB proinflammatory cascade signaling.

Microglia-mediated neuroinflammatory responses are recognized as a predominant factor during high intraocular pressure (IOP)-induced retinal and optic nerve injury along with potential therapeutic targets for the disease. Our previous research indicated that mesenchymal stem cell (MSC) treatment could reduce high IOP-induced neuroinflammatory responses through the TLR4 pathway in a rat model without apparent cell replacement and differentiation, suggesting that the anti-neuroinflammatory properties of MSCs are potentially mediated by paracrine signaling. This study aimed to evaluate the anti-neuroinflammatory effect of human adipose tissue-derived extracellular vesicles (ADSC-EVs) in microbead-induced ocular hypertension (OHT) animals and to explore the underlying mechanism since extracellular vesicles (EVs) are the primary transporters for cell secretory action. The anti-neuroinflammatory effect of ADSC-EVs on LPS-stimulated BV-2 cells in vitro and OHT-induced retinal and optic nerve injury in vivo was investigated. According to the in vitro research, ADSC-EV treatment reduced LPS-induced microglial activation and the TLR4/NF-κB proinflammatory cascade response axis in BV-2 cells, such as CD68, iNOS, TNF-α, IL-6, and IL-1ß, TLR4, p-38 MAPK, NF-κB. According to the in vivo data, intravitreal injection of ADSC-EVs promoted RGC survival and function, reduced microglial activation, microglial-derived neuroinflammatory responses, and TLR4/MAPK/NF-κB proinflammatory cascade response axis in the OHT mice. Our findings provide preliminary evidence for the RGC protective and microglia-associated neuroinflammatory reduction effects of ADSC-EVs by inhibiting the TLR4/MAPK/NF-κB proinflammatory cascade response in OHT mice, indicating the therapeutic potential ADSC-EVs or adjunctive therapy for glaucoma.

Acute stress regulates phosphorylation of N-methyl-d-aspartate receptor GluN2B at S1284 in hippocampus.

Exposure to acute stress leads to diverse changes, which include either beneficial or deleterious effects on molecular levels that are implicated in stress-related disorders. N-methyl-d-aspartate receptor (NMDAR)-mediated signalings, are thought to be vital players in stress-related mental disorders as well as attractive therapeutic targets for clinical treatment. In the present study, we utilized acute stress models in mice to explore regulation of phosphorylation level of S1284 in GluN2B subunit of NMDAR. We found out that forced swimming and acute restraint stress increased phosphorylation level of S1284, while phosphorylation level of S1284 was unaltered after brief exposure to open field. Moreover, phosphorylation change of S1284 was negated by treatment of roscovitine which is believed to be a Cyclin-dependent kinase inhibitor. Besides, we showed well correlation of phosphorylation change of S1284 and immobility time during forced swimming. Collectively, our results demonstrated that phosphorylation level of S1284 in GluN2B was regulated by acute stress.

FIGO stage IV gestational choriocarcinoma misdiagnosed as pulmonary tuberculosis: A case report.

Choriocarcinoma is a rare, highly malignant neoplasm, which may occur during or following any type of pregnancy. This tumor often demonstrates rapid hematogenous spread to multiple organs, and is associated with high human chorionic gonadotropin (HCG) levels and a good response to chemotherapy. In the present study, the case of a 29-year-old female with distant metastatic choriocarcinoma [International Federation of Gynecology and Obstetrics (FIGO) stage IV; World Health Organization score, 15], who was misdiagnosed with pulmonary tuberculosis at a local hospital is presented. The major failure in the diagnosis of this case was that the patient's serum ß-HCG levels were ignored initially. However, the patient received combined treatment with systematic multi-agent chemotherapy, whole-brain radiation therapy and gross total resection of the brain lesion at West China Second Hospital, and achieved complete remission. In conclusion, the accurate and prompt diagnosis of choriocarcinoma is crucial for a good outcome. Furthermore, in young female patients exhibiting symptoms such as pulmonary bleeding or neurological disturbances following a hydatidiform mole or a normal pregnancy, even in the absence of abnormal uterine bleeding, serum ß-HCG levels must be analyzed and a diagnosis of choriocarcinoma must be considered.