Articles: human.
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Chinese medical journal · Feb 2025
Driving effect of P16 methylation on telomerase reverse transcriptase-mediated immortalization and transformation of normal human fibroblasts.
P16 inactivation is frequently accompanied by telomerase reverse transcriptase ( TERT ) amplification in human cancer genomes. P16 inactivation by DNA methylation often occurs automatically during immortalization of normal cells by TERT . However, direct evidence remains to be obtained to support the causal effect of epigenetic changes, such as P16 methylation, on cancer development. This study aimed to provide experimental evidence that P16 methylation directly drives cancer development. ⋯ P16 methylation drives TERT -mediated immortalization and transformation of normal human cells that may contribute to cancer development.
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Pediatric emergency care · Feb 2025
Changes in Seasonal Patterns for Common Pediatric Respiratory Viruses During the COVID Pandemic.
Observed alterations in seasonal patterns of common pediatric respiratory viruses during and immediately after the COVID-19 pandemic had far-reaching implications for the care of ill children. Here, we quantify the effects of the pandemic and related nonpharmaceutical interventions on the prevalence and seasonality of common pediatric respiratory illnesses. ⋯ Our observations add to the growing body of literature supporting the hypothesis that human interactions are one of the key drivers of pediatric respiratory viral seasonality in addition to climate. Understanding the effect of human interactions on disease spread is crucial for the development of effective mitigation measures for future pandemics while avoiding dangerous spikes of other illnesses once those interventions are lifted.
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Human experimental studies have shown that levcromakalim, an ATP-sensitive potassium (K ATP ) channel opener, induces migraine attacks in people with migraine but not in healthy volunteers. However, the exact site of action for K ATP channels in migraine pathophysiology remains unclear. This study investigates the role of these channels in the meninges in eliciting behavioral hypersensitivity responses in mice. ⋯ Finally, dural coinjection of glibenclamide inhibited periorbital hypersensitivity induced by CGRP or prolactin in female mice. These studies demonstrate that the meninges can be one site of action for the migraine-triggering effects of K ATP channel openers. They also show that NO donors, CGRP, and prolactin can produce behavioral hypersensitivity through opening of K ATP channels in the meninges.
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Anesthesia and analgesia · Feb 2025
ReviewA Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity.
Although anesthesia makes painful or uncomfortable diagnostic and interventional health care procedures tolerable, it may also disrupt key cellular processes in neurons and glia, harm the developing brain, and thereby impair cognition and behavior in children. Many years of studies using in vitro, animal behavioral, retrospective database studies in humans, and several prospective clinical trials in humans have been invaluable in discerning the potential toxicity of anesthetics. The objective of this scoping review was to synthetize the evidence from preclinical studies for various mechanisms of toxicity across diverse experimental designs and relate their findings to those of recent clinical trials in real-world settings.
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The lancet oncology · Feb 2025
Multicenter StudyClaudin 18.2-targeting antibody-drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial.
CMG901 is a novel first-in-class antibody-drug conjugate with a humanised anticlaudin 18.2 antibody linked to microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the antitumour activity and safety of CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer and other solid tumours. ⋯ KYM Biosciences.