Articles: function.
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Epigenetics refers to how gene expression and function are modulated without modifying the DNA sequence but through subtle molecular changes or interactions with it. As spermatogenesis progresses, male germ cells suffer plenty of epigenetic modifications, resulting in the definitive epigenome of spermatozoa conditioning its functionality, and this process can be altered by several internal and external factors. The paternal epigenome is crucial for sperm function, fertilization, embryo development, and offspring's health, and altered epigenetic states are associated with male infertility with or without altered semen parameters, embryo quality impairment, and worse ART outcomes together with the future offspring's health risks mainly through intergenerational transmission of epigenetic marks. ⋯ In this review, we discuss the mechanisms of epigenetics in sperm and how epigenetics behave during spermatogenesis. Additionally, we elaborate on the relationship of sperm epigenetics with sperm parameters and male infertility, and highlight the impact of sperm epigenetic alterations on sperm parameters, embryo quality, ART outcomes, miscarriage rates and offspring's health. Furthermore, we provide insights into the future research of epigenetic alterations in male infertility.
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Clinical Trial
Dynamic cerebral autoregulation during step-wise increases in blood pressure during anaesthesia: A nonrandomised interventional trial.
Classically, cerebral autoregulation (CA) entails cerebral blood flow (CBF) remaining constant by cerebrovascular tone adapting to fluctuations in mean arterial pressure (MAP) between ∼60 and ∼150 mmHg. However, this is not an on-off mechanism; previous work has suggested that vasomotor tone is proportionally related to CA function. During propofol-based anaesthesia, there is cerebrovascular vasoconstriction, and static CA remains intact. Sevoflurane-based anaesthesia induces cerebral vasodilation and attenuates CA dose-dependently. It is unclear how this translates to dynamic CA across a range of blood pressures in the autoregulatory range. ⋯ During general anaesthesia, dynamic CA is dependent on MAP, also within the autoregulatory range. This phenomenon was more pronounced during propofol anaesthesia than during sevoflurane.
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Neuronal N-type (Ca V 2.2) voltage-gated calcium channels are essential for neurotransmission from primary afferent terminals in the dorsal horn. In this study, we have used a knockin mouse containing Ca V 2.2 with an inserted extracellular hemagglutinin tag (Ca V 2.2_HA), to visualise the pattern of expression of endogenous Ca V 2.2 in dorsal root ganglion (DRG) neurons and their primary afferents in the dorsal horn. We examined the effect of partial sciatic nerve ligation (PSNL) and found an increase in Ca V 2.2_HA only in large and medium dorsal root ganglion neurons and also in deep dorsal horn synaptic terminals. ⋯ We also found that following PSNL, there is patchy loss of glomerular synapses immunoreactive for Ca V 2.2_HA and CGRP or IB4, restricted to the superficial layers of the dorsal horn. This reduction is not dependent on α 2 δ-1 and likely reflects partial deafferentation of C-nociceptor presynaptic terminals. Therefore, in this pain model, we can distinguish 2 different events affecting specific DRG terminals, with opposite consequences for Ca V 2.2_HA expression and function in the dorsal horn.
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Anesthesia and analgesia · Jun 2023
Alfaxalone Alleviates Neurotoxicity and Cognitive Impairment Induced by Isoflurane Anesthesia in Offspring Rats.
The anesthetic isoflurane can cause neurotoxicity in fetuses and offspring of rats, affecting their neurodevelopment. However, the underlying mechanisms and therapeutic targets of isoflurane-induced neurotoxicity remain to be identified. Alfaxalone (ALF) is a steroid anesthetic. Steroids have been reported to have neuroprotective effects. This study aimed to investigate whether ALF could alleviate the isoflurane-induced neurotoxicity in fetuses and offspring of rats. ⋯ Based on these findings, this study suggested that isoflurane exposure during pregnancy in rats could cause neuroinflammation and death of embryos as well as impairment of cognitive function in the offspring rats. ALF can be used to counteract the negative effects of isoflurane.
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Many studies have found that viral infections affect different tissues, including the inner ear. Coronavirus disease 2019 (COVID-19), a viral infection, is a significant health problem worldwide. Prestin is a motor protein with important functions both in the outer hair cells of the inner ear and in cardiac tissue. In addition, prestin is promising as an early biomarker in the detection of ototoxicity. To determine the severity of infection in COVID-19 patients and to determine whether other tissues are affected by the infection, lactate dehydrogenase (LDH), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase MB (CK-MB), biochemical markers such as ferritin and D-dimer are used. This study aimed to compare prestin levels in patients with COVID-19 and healthy volunteers. ⋯ The levels of prestin, a motor protein in inner ear outer hair cells and cardiac myocytes, were found to be higher in COVID-19 patients than in healthy volunteers. It also showed a positive correlation with CRP and D-dimer. This may be associated with systemic dysfunction.