The peroxynitrite-mediated activation of matrix metalloproteinase-2 (MMP-2) and subsequent cleavage of troponin I (TnI) in ventricular myocytes is a detrimental effect of ischemia/reperfusion injury. We hypothesized that acetaminophen, an effective antioxidant against peroxynitrite, would attenuate activation of MMP-2 and improve cardiac mechanical function. Isolated, perfused guinea pig hearts (Langendorff) were treated with either acetaminophen [0.35 mmol/l] or its vehicle and administered a bolus injection of peroxynitrite (6 microM) after reaching steady state function. Hemodynamic, metabolic, and mechanical effects were recorded, and coronary effluent concentrates or supernatant from heart homogenates were subjected to Western blotting and gelatin zymography. Hemodynamic and metabolic data showed no difference between acetaminophen- and vehicle-treated hearts. Mechanical data revealed that treatment with acetaminophen preserved contractile function (particularly diastolic function) after peroxynitrite administration. For example, 5 min after administration of peroxynitrite percent baseline -dP/dt(max) was 10+/-3% and -4+/-7% (P<0.05) in acetaminophen- and vehicle-treated hearts, respectively. Western blotting and gel zymography revealed higher 72 kDa (pro-MMP-2) proteolytic activity in heart homogenates of vehicle-treated versus acetaminophen-treated hearts. In addition, Western blotting of heart homogenates showed increased degradative products of TnI in vehicle-treated versus acetaminophen-treated hearts. We conclude that acetaminophen is cardioprotective, at least in part, by attenuating peroxynitrite-activated, MMP-2-mediated cleavage of TnI.
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http://dx.doi.org/10.1016/j.yjmcc.2006.01.010 | DOI Listing |
Lasers Med Sci
January 2025
Hangzhou Third People's Hospital, Hangzhou, China.
Background: Post-inflammatory hyperpigmentation (PIH) is a common cosmetic concern, often leading to significant psychological distress for the patients. With the widespread application of lasers including ablative fractional resurfacing (AFR) with a 10,600 nm CO laser, PIH caused by lasers is becoming increasingly common. But due to the absence of an appropriate animal research model, our understanding of pathophysiological mechanisms and preventive strategies for PIH remains limited.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
ENT Institute and Department of Otolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, 200031, China.
Tinnitus, a widespread condition affecting numerous individuals worldwide, remains a significant challenge due to limited effective therapeutic interventions. Intriguingly, patients using cochlear implants (CIs) have reported significant relief from tinnitus symptoms, although the underlying mechanisms remain unclear and intracochlear implantation risks cochlear damage and hearing loss. This study demonstrates that targeted intracochlear electrical stimulation (ES) in guinea pigs with noise-induced hearing loss reversed tinnitus-related maladaptive plasticity in the cochlear nucleus (CN), characterized by reduced auditory innervation, increased somatosensory innervation, and diminished inhibitory neural networks.
View Article and Find Full Text PDFLipids
January 2025
Molecular Biology Institute, University of California, Los Angeles, California, USA.
The order Rodentia comprises nearly 45% of all extant taxa, currently organized into 31 living families, some 450 genera, and roughly 2010 species (Kelt & Patton, 2020). Considering that rodents began evolving at least 66 million years ago, it is not surprising that they have diversified into five distinct suborders. With the advent of molecular biology, this difference can often be seen at the molecular level as well.
View Article and Find Full Text PDFOtol Neurotol
January 2025
Department of Otolaryngology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Hypothesis: Extracochlear electric-acoustic stimulation (EAS) between the round window membrane and the basal part of the cochlear bone exhibits distinct auditory brainstem response (ABR) characteristics.
Background: The use of EAS in individuals with residual hearing is becoming increasingly common in clinical settings. Ongoing research has explored the characteristics of EAS-induced responses in hearing cochleae.
Stem Cell Reports
December 2024
Center for Cell Lineage and Development, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China, Guangzhou Medical University, Guangzhou 511436, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, P.R. China. Electronic address:
Guinea pigs are valuable models for human disease research, yet the lack of established pluripotent stem cell lines has limited their utility. In this study, we isolate and characterize guinea pig epiblast stem cells (gpEpiSCs) from post-implantation embryos. These cells differentiate into the three germ layers, maintain normal karyotypes, and rely on FGF2 and ACTIVIN A signaling for self-renewal and pluripotency.
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