Biomedical Journal最新文献

Background: Obesity and circadian rhythm disruption are significant global health concerns, contributing to an increased risk of metabolic disorders. Both adipose tissue and circadian rhythms play critical roles in maintaining energy homeostasis, and their dysfunction is closely linked to obesity. This study aimed to assess the effects of chronic low-dose SR9009, a REV-ERB ligand, on circadian disruption induced by constant light exposure in mice.

Material and methods: Mice were exposed to constant light for eight weeks (LL mice), resulting in increased body weight, insulin resistance, white fat mass, and altered circadian clock gene expression. Low-dose SR9009 (10 mg/kg daily) was administered chronically to assess its impact on these metabolic disruptions.

Results: LL mice treated with SR9009 for eight weeks showed reduced weight gain, insulin resistance, and white fat mass but no significant impact on overall energy homeostasis. SR9009 suppressed Bmal1 expression and restored Rev-erbα and Rev-erbβ expression in white and brown adipose tissue (WAT and BAT). In vitro studies using 3T3-L1 cells indicated that SR9009 inhibited adipogenesis, leading to further investigation in vivo. SR9009 restored ChREBP1a and Srebp-1c expression in BAT but did not affect inflammatory cytokine or adipokine gene expression, nor did it restore Fasn, Pparγ, and Prom1 expression in both WAT and BAT.

Conclusions: These findings suggest that SR9009 may be a potential therapeutic for preventing weight gain and insulin resistance caused by circadian disruptions, likely through adipogenesis inhibition, though its effects on other metabolic pathways remain limited at low doses.

Theileria parasites are known to induce the transformation of host bovine leukocytes, involved in rapid proliferation, evasion from apoptotic mechanisms, and increased dissemination. In this study, we reveal the involvement of m⁶A RNA modification in T. annulata infection-induced transformation of bovine leukocytes. We conducted m⁶A sequencing and bioinformatics analysis to map the mRNA methylation patterns of T. annulata-infected host leukocytes. We observe specific mRNA modifications for T. annulata-infected leukocytes and a strong correlation between the proliferation rate of the infected Leukocytes with m⁶A modifications We observe that the increased amounts of m⁶A seem to impact some cell cycle dynamics, potentially via modifications of E2F4 mRNA. Moreover, we further identify HIF-1α as a possible driver of these m⁶A RNA modifications that have clear relevance to cellular proliferation dynamics. Overall, our results provide insights into the role of m6A mRNA methylation in the molecular crosstalk between Theileria and their host leukocytes, emphasizing the critical role of mRNA methylation in host-parasite interaction.

The circadian system is composed by a central hypothalamic clock at the suprachiasmatic nuclei (SCN) that communicates with peripheral circadian oscillators for daily coordination of behavior and physiology. The SCN entrain to the environmental 24-h light-dark (LD) cycle and drive daily rhythms of internal synchronizers such as core body temperature, hypothalamic-hypophysary hormones, sympathetic/parasympathetic activity, as well as behavioral and feeding-fasting rhythms, which supply signals setting core molecular clocks at central and peripheral tissues. Steady phase relationships between the SCN and peripheral oscillators keep homeostatic processes such as microbiota/microbiome composition/activity, metabolic supply/demand, energy balance, immunoinflammatory process, sleep amount and quality, psychophysiological stress, etc. Indeed, the risk of health alterations increase when these phase relationships are chronically changed prompting circadian disruption (CD), as occurring after sudden LD cycle changes (so-called jet-lag), or due to changes of activity/feeding-rest/fasting rhythm with respect to LD cycles (as humans subjected to nightwork, or restricting food access at rest in mice). Typical pathologies observed in animal models of CD and epidemiological studies include metabolic syndrome, type-2 diabetes, obesity, chronic inflammation, cancer, sleep disruption, decrease in physical and cognitive performance, and mood, among others. The present review discusses different aspects of such physiological dysregulations observed in animal models of CD having altered feeding-fasting rhythms, with potential translation to human health.

Sleep is crucial for sustaining normal physiological functions, and sleep deprivation has been associated with increased pain sensitivity. The histone deacetylases (HDACs) are known to significantly regulate in regulating neuropathic pain, but their involvement in nociceptive hypersensitivity during sleep deprivation is still not fully understood. Utilizing a modified multi-platform water environment technique to establish a sleep deprivation model. We measured the expression levels of HDAC1/2 in the medial prefrontal cortex (mPFC) through immunoblotting and real-time quantitative PCR. The presence of pyroptosis was determined using a TUNEL assay. Suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor employed clinically, was injected into the peritoneal cavity to inhibit HDAC2 expression. Animal pain behaviors were evaluated by measuring paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs). Our findings indicate that sleep deprivation leads to increased nociceptive hypersensitivity, an upregulation of HDAC2 expression in the mPFC, a downregulation of the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and changes in markers of oxidative stress in rats. SAHA, the HDAC inhibitor, enhanced NRF2 expression by inhibiting HDAC2, which consequently ameliorated oxidative stress and mitigated nociceptive hypersensitivity in rats. The incidence of apoptosis was found to be higher in the mPFC tissues of sleep deprivation rats, and the intraperitoneal administration of SAHA decreased this apoptosis. The co-injection of SAHA and the NRF2 inhibitor ML385 into sleep deprivation rats negated the beneficial effects of SAHA. In conclusion, HDAC2 is implicated in the induction of oxidative stress and apoptosis by suppressing NRF2 levels, thereby exacerbating nociceptive hypersensitivity in sleep deprivation rats.

The circadian rhythm controls a wide range of functions in the human body and is required for optimal health. Disruption of the circadian rhythm can produce inflammation and initiate or aggravate chronic diseases. The modern lifestyle involves long indoor hours under artificial lighting conditions as well as eating, working, and sleeping at irregular times, which can disrupt the circadian rhythm and lead to poor health outcomes. Seasonal solar variations, the sunspot cycle and anthropogenic electromagnetic fields can also influence biological rhythms. The possible mechanisms underlying these effects are discussed, which include resonance, radical-pair formation in retina cryptochromes, ion cyclotron resonance, and interference, ultimately leading to variations in melatonin and cortisol. Intracellular water, which represents a coherent, ordered phase that is sensitive to infrared light and electromagnetic fields, may also respond to solar variations and man-made electromagnetic fields. We describe here various factors and underlying mechanisms that affect the regulation of biological rhythms, with the aim of providing practical measures to improve human health.

The integration of Extended Reality (XR) technologies, including Augmented Reality (AR) and Virtual Reality (VR), represents a significant advancement in pediatric neurosurgery. These technologies offer immersive and interactive 3D visualization capabilities, which enhance the precision and accuracy of surgical procedures. This comprehensive review systematically examines the current applications of XR in pediatric neurosurgery. The review adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, which provide criteria for reporting systematic reviews and meta-analyses. It also utilizes the PICOS (Population, Intervention, Comparison, Outcome, Study design) framework to formulate research questions and structure literature searches. A thorough search of multiple databases yielded 1,434 relevant articles, supplemented by an additional 55 articles obtained through manual searches. The review includes a detailed analysis of the XR workflow, its surgical applications, and associated outcomes. It emphasizes the practical benefits of XR in preoperative planning, intraoperative navigation, and postoperative assessment. Furthermore, the paper discusses the challenges, opportunities, and future prospects of XR in pediatric neurosurgery, including its effects on surgical outcomes, medical education, and patient care. By synthesizing technological developments with clinical applications, this review provides a comprehensive understanding of the multifaceted roles of AR and VR in pediatric neurosurgical practice. It covers innovative methods, applicable scenarios, datasets, and metrics, along with a comparative analysis of state-of-the-art techniques, considering differences in input data. Ultimately, this review aims to present an overview of the current landscape of XR in pediatric neurosurgery to inform future research and clinical practice.

This review presents a comprehensive perspective on the genomic surveillance of SARS-CoV-2 in Taiwan, with a focus on next-generation sequencing and phylogenetic interpretation. This article aimed to explore how Taiwan has utilized genomic sequencing technologies and surveillance to monitor and mitigate the spread of COVID-19. We examined databases and sources of genomic sequences and highlighted the role of data science methodologies in the explanation and analyses of evolutionary data. This review addressed the challenges and limitations inherent in genomic surveillance, such as concerns regarding data quality and the necessity for interdisciplinary expertise for accurate data interpretation. Special attention was given to the unique challenges faced by Taiwan, including its high population density and major transit destination for international travelers. We underscored the far-reaching implications of genomic surveillance data for public health policy, particularly in influencing decisions regarding travel restrictions, vaccine administration, and public health decision-making. Studies were examined to demonstrate the effectiveness of using genomic data to implement public health measures. Future research should prioritize the integration of methodologies and technologies in evolutionary data science, particularly focusing on phylodynamic analytics. This integration is crucial to enhance the precision and applicability of genomic data. Overall, we have provided an overview of the significance of genomic surveillance in tracking SARS-CoV-2 variants globally and the pivotal role of data science methodologies in interpreting these data for effective public health interventions.

Background: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and related to endothelial activation and systemic inflammation. Herein, we investigate the pathophysiological mechanisms of AF through endothelial activation and cell-cell interactions related to the development of POAF.

Methods: Patients without previous AF undergoing cardiac surgery were studied. Permanent AF patients were included as positive controls. Interleukin (IL)-6, Von Willebrand factor (vWF), N-terminal pro-brain natriuretic peptide (NT-proBNP) and high sensitivity troponin T (hsTnT) were evaluated by electrochemiluminescence. Vascular cell adhesion molecule-1 (VCAM-1) and human Growth Differentiation Factor 15 (GDF-15) was assessed by ELISA. Connexins (Cxs) 40 and 43 were measured by tissue immunolabelling, and apoptosis by TUNEL assay.

Results: We included 117 patients (median age 67: 27.8% female): 17 with permanent AF; 27 with POAF and 73 with non- AF. Patients with permanent AF and POAF had higher levels of NT-proBNP, hs-TnT, apoptotic nuclei and decrease Cx43 expression, compared to non-AF patients (all p-value <0.05). VCAM-1 and GDF-15 were significantly higher in permanent AF vs. non-AF (p=0.013 and p=0.035).

Conclusions: Greater endothelial activation and inflammation in AF patients compared to those without AF was found. The proinflammatory state in AF patients, in addition to the lower expression of Cx43, seems to be associated with atrial remodeling processes occurring in AF.