Dimethyl sulfoxide (DMSO) is a polar organic solvent that is used to dissolve neuroprotective or neurotoxic agents in neuroscience research. However, DMSO itself also has pharmacological and pathological effects on the nervous system. Astrocytes play a central role in maintaining brain homeostasis, but the effect and mechanism of DMSO on astrocytes has not been studied. The present study showed that exposure of astrocyte cultures to 1% DMSO for 24 h did not significantly affect cell survival, but decreased cell viability and glial glutamate transporter expression, and caused mitochondrial swelling, membrane potential impairment and reactive oxygen species production, and subsequent cytochrome c release and caspase-3 activation. DMSO at concentrations of 5% significantly inhibited cell variability and promoted apoptosis of astrocytes, accompanied with more severe mitochondrial damage. These results suggest that mitochondrial impairment is a primary event in DMSO-induced astrocyte toxicity. The potential cytotoxic effects on astrocytes need to be carefully considered during investigating neuroprotective or neurotoxic effects of hydrophobic agents dissolved by DMSO.
We intended to explore the effect of miR-202-5p and phosphatase and tensin homolog (PTEN) on doxorubicin (DOX) resistance of breast cancer cells. The result of quantitative reverse transcription-polymerase chain reaction (qRT-PCR) reveals that miR-202-5p was highly expressed in drug-resistant breast cancer tissues, while PTEN was expressed less. MiR-202-5p directly targeted PTEN. Further, it was found that the overexpression of miR-202-5p promoted the DOX resistance and proliferation as well as decreased apoptosis of MCF-7 cells. The lower expression of miR-202-5p inhibited DOX resistance and proliferation as well as increased the apoptosis of MCF-7/DOX cells. In vivo experiments showed that mice with downregulated miR-202-5p had smaller tumor volume and lower Ki67 level. The overexpression of PTEN declined the proliferation of MCF7 cells, while miR-202-5p's overexpression could offset the function of overexpression of PTEN. The knockdown of PTEN promoted MCF7/DOX cell proliferation that could be counteracted by miR-202-5p silence. Moreover, we also revealed that downregulated miR-202-5p expression inhibited PI3k/Akt signaling pathway-related protein by regulating expression of PTEN.
Background:This study investigates the clinical effects of sealing the femoral canal by intramedullary alignment instrumentation in total knee arthroplasty (TKA).Methods:One hundred twenty consecutive patients with knee osteoarthritis, who underwent unilateral TKA, were enrolled in the study and equally randomized into 2 groups: the sealing group and the control group. In the sealing group, the femoral canal was sealed with autogenous bone and cement using intramedullary alignment instrumentation, while the femoral hole was left open for patients in the control group. Blood loss, hemoglobin (Hb) reduction, and other parameters were recorded, as well as the duration of hospital stay and complications. The Hospital for Special Surgery (HSS) knee score was used to assess knee function at the final follow-up appointment.Results:The calculated blood loss, hidden blood loss, transfusion requirements, drainage volume, and Hb reduction measurements were significantly different (P < .05) between the 2 groups. There were no significant differences in the surgery time, intraoperative blood loss, length of hospital stay, HSS score or complications between the 2 groups (P > .05).Conclusions:Sealing the intramedullary canal with autologous bone and a cement plug is an effective method for reducing blood loss and decreasing blood transfusion requirements during TKA procedures that have increasing complication rates.
Background: Chemokines play a key role in post-traumatic inflammation and secondary injury after spinal cord injury (SCI). CCL28, the chemokine CC-chemokine ligand 28, is involved in the epithelial and mucosal immunity. However, whether CCL28 participates in the physiopathologic processes after SCI remains unclear.Results: CCL28 is upregulated in the spinal cord after SCI. In addition, neutralizing antibodies against IL-1β or TNF-α, or treatment of ML120B, a selective inhibitor of IKK-β, remarkably decrease CCL28 upregulation, suggesting that CCL28 upregulation relies on NF-κB pathway activated by IL-1β and TNF-α after SCI. Moreover, CD4+CD25+FOXP3+ regulatory T (Treg) cells that express CCR10, a receptor of CCL28, are enriched in the spinal cord after SCI. We further demonstrate that the spinal cord recruits Treg cells through CCL28-CCR10 axis, which in turn function to suppress immune response and promote locomotor recovery after SCI. In contrast, neutralizing CCL28 or CCR10 reduces Treg cell recruitment and delays locomotor recovery.Methods: The neutralizing antibodies and recombinant CCL28 were injected intraspinally into the mice prior to SCI, which was established via hemitransection. RT-qPCR analysis was performed to determine transcript level, and Western blot analysis and ELISA assay were used to detect protein expression. Immune cells were analyzed by flow cytometry and visualized by immunofluorescence. The chemotaxis was assessed by in vitro transwell migration assay. The mouse locomotor activity was assessed via the Basso Mouse Scale (BMS) system.Conclusions: These results indicate that NF-κB pathway-regulated CCL28 production plays a protective role after SCI through recruiting CCR10-expressing and immunosuppressive Treg cells, and suggest that interfering CCL28-CCR10 axis might be of potential clinical benefit in improving SCI recovery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.