MgSO₄ as a novel hypothermia infusion solution promotes ischemic stroke recovery through Ca²⁺ regulation of neurovascular units

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1896 - 1913

Published: Jan. 2, 2025

The neuroprotection of acute ischemic stroke (AIS) patients to alleviate the reperfusion injury is a long-standing problem. Although intra-arterial selective cooling saline infusion (IA-SCSI) promising technique improve outcome AIS, clinical results are not sufficiently satisfactory. Magnesium-containing solutions such as magnesium sulfate (MgSO4) can protect cells by modulating intracellular Ca2+ content in damaged cells, suggesting that they could be hypothermia solution. In this study, we hypothesized MgSO4, novel solution (IA-SCMI), promote AIS recovery. Methods: First, IA-SCMI was performed rats subjected middle cerebral artery occlusion. effect combined and MgSO4 treatment on different neurovascular (NVU) after oxygen-glucose deprivation/reoxygenation (OGD/R) examined. Results: Compared with IA-SCSI or IA-MgSO4 alone, offered best protective improving neurological defects, alleviating brain integrity damage CBF reduction. Meanwhile, vitro revealed combination provided maximum protection NVU mainly achieved through regulation homeostasis cells. Conclusion: may facilitate recovery function patients.

Language: Английский

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GsMTx-4 combined with exercise improves skeletal muscle structure and motor function in rats with spinal cord injury

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0317683 - e0317683

Published: Jan. 22, 2025

Motor dysfunction and muscle atrophy are typical symptoms of patients with spinal cord injury (SCI). Exercise training is a conventional physical therapy after SCI, but exercise intervention alone may have limited efficacy in reducing secondary promoting nerve regeneration functional remodeling. Our previous research found that intramedullary pressure SCI one the key factors affecting prognosis. It has been reported GsMTx-4, specific blocker mechanosensitive ion channels Piezo1, can protect integrity neuromuscular junction promote regeneration, thus potential as therapeutic agent for SCI. In this study, we observed combined separate effect GsMTx-4 on structure soleus motor function rats At 42 days post-injury, compared rats, Basso–Beattie–Bresnahan score (P = 0.0007) Gait Symmetry 0.0002) were significantly improved combination therapy. On histology rat muscle, treatment increased wet weight ratio, fiber cross-sectional area acetylcholinesterase (all P<0.0001). tissue, neuron counts BDNF levels, reduced percentage TUNEL-positive cells physiology succinate dehydrogenase expression (P<0.0001), while α-glycerophosphate (P<0.0001) GDF8 protein 0.0008) decreased. Results indicate effectively improves histopathology enhancing function. This study was conducted animal models, it offers insights treatment, advancing understanding lower limb pathology post-SCI. Further needed clinical validation future.

Language: Английский

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Inhibition of autophagy promotes ultrasound‑targeted microbubble destruction-induced apoptosis of pancreatic cancer cells

International Journal of Medical Sciences, Journal Year: 2025, Volume and Issue: 22(7), P. 1708 - 1719

Published: March 3, 2025

In therapeutic studies of pancreatic cancer, ultrasound-targeted microbubble destruction (UTMD) has shown potential in promoting apoptosis as a safe and non-invasive adjuvant therapy. Autophagy, regulatory mechanism for cellular stress response survival, plays dual role tumor development, progression, treatment. However, the autophagy UTMD-induced cancer cells remains unclear. this study, chloroquine (CQ), an inhibitor, was combined with UTMD to treat both vitro vivo, changes assessed through Western blot TUNEL staining. The results showed that induced cells. Notably, inhibiting significantly enhanced apoptosis, while inhibition did not affect autophagy. These findings suggest reduces effectiveness treating cancer. This study offers new perspective on suggesting combining inhibitors could be promising strategy enhance

Language: Английский

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Endothelial Piezo1 stimulates angiogenesis to offer protection against intestinal ischemia–reperfusion injury in mice

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: April 22, 2025

Abstract Background Intestinal ischemia–reperfusion (I/R) injury, which occurs in the ileum and not only leads to intestinal tissue damage, but also may trigger systemic inflammatory responses, is a prevalent pathological condition that typically associated with acute ischemia, surgical procedures, or trauma. However, precise underlying pathogenic mechanisms have yet been fully uncovered. In this study, we explored specific roles by endothelial Piezo1 involved I/R injury. Methods We evaluated of using both vivo mouse injury vitro hypoxia-reoxygenation (H/R) models. The expression was assessed immunofluorescence RT-qPCR. experiments involving knockout activation agonist Yoda1 were conducted observe effects on angiogenesis Results found post-intestinal mice, markedly increased mainly abundant cells. Specific exhibited more severe phenotype characterized accelerating damage structure, increasing response, inhibiting angiogenesis. Yoda1-mediated significantly ameliorated Activation induced H/R promoted Human Umbilical Vein Endothelial Cells (HUVECs), inhibited GsMTx4. mediated linked an increase extracellular Ca 2+ influx, turn enhanced hypoxia-inducible factor 1 alpha (HIF-1α) signaling pathway. Conclusions Our findings indicate plays crucial role protecting against promoting cells, possibly through /HIF-1α/VEGF This suggests targeting channels could be therapeutic strategy for

Language: Английский

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