The FASEB Journal最新文献

The COVID-19 pandemic revealed reduced vaccine efficacy and worse outcomes in people with type 2 diabetes mellitus (T2DM). However, how T2DM, independent of obesity, alters immune responses and lymphoid organ architecture remains unclear. We evaluated antibody production and lymphoid organ morphology following SARS-CoV-2 antigen immunization in Goto-Kakizaki (GK) rats, a non-obese T2DM model, to evaluate the isolated effect of diabetes. Ten-week-old male Wistar and GK rats received three intramuscular injections of SARS-CoV-2 antigens at 15-day intervals. Two antigen formulations were used: chemically inactivated whole SARS-CoV-2 containing aluminum hydroxide adjuvant and an inactivated Newcastle virus engineered to express the SARS-CoV-2 spike protein. Fifteen days after the final dose, anti-Spike IgG titers were measured by ELISA, and histological and morphometric analyses of lymphoid tissues were performed. GK rats exhibited elevated anti-Spike IgG responses compared with WT controls, regardless of the antigen formulation. Distinct morphological alterations in the lymphoid organs accompanied the enhanced IgG responses. Mesenteric lymph nodes from GK rats exhibited a morphology similar to that of WT rats. The thymus exhibited features of involution, including septal thickening, reduced corticomedullary distinction, diminished cortical cellularity, cortical thinning, and medullary expansion. The spleen showed white pulp remodeling, characterized by enlargement of germinal centers and periarteriolar lymphoid sheaths, along with a reduction in the marginal zone. We described herein the remodeling of the primary and secondary lymphoid organs in non-obese diabetic GK rats, which may play a role in the antibody response to an immune challenge.

Thyroid hormones (THs) are endocrine factors that play an important role in brain development by modulating several neurodevelopmental processes, including neuronal migration, synaptogenesis, and myelination. Therefore, adequate regulation of these hormones is important for the structure and function of the brain. Recently, a close association between THs deficiency or dysfunction has been found with several neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). These results imply that thyroid hormones play an important role in the occurrence of neurodevelopmental disorders. In this review, we thoroughly investigate the biosynthetic pathways and regulatory mechanisms involved in thyroid hormones production. We also assess the importance of thyroid hormones during different periods of brain development, as well as the underlying molecular processes. Finally, we extend our discussion to explore the relationship between thyroid hormones and neurodevelopmental disorders. The objective is to provide mechanistic and clinical insights and to identify promising research avenues that could facilitate earlier diagnosis and intervention for these conditions.

The global incidence of metabolic disorders has shown a significant upward trend, with growing evidence suggesting a strong association between their development and maternal environmental factors during gestation, including dietary patterns. This study investigated the effects of maternal fructose consumption during pregnancy on hepatic glucose metabolism in male mouse offspring. The results revealed that downregulation of glucokinase expression was closely associated with impaired glucose metabolism in the liver tissue of the offspring. Furthermore, DNA Methyltransferase 3 beta (DNMT3B)-mediated hypermethylation of the glucokinase (GCK, protein: GK) promoter region was responsible for this transcriptional repression. This study established that maternal fructose intake during pregnancy led to reduced GK expression through DNMT3B-dependent epigenetic modifications, resulting in abnormal glucose metabolism. Importantly, pharmacological intervention with a GK activator effectively ameliorated these metabolic abnormalities. Besides, the expression of DNMT3B was regulated by CCAAT Enhancer Binding Protein Beta (C/EBPβ) at the transcriptional level. In brief, this study demonstrated that maternal fructose intake has a negative effect on glucose metabolism in the liver of offspring and highlights the importance of dietary guidance during pregnancy and diabetes prevention.

The acute effects of exercise on brain energy metabolism are poorly understood. We used dynamic proton magnetic resonance spectroscopy (¹H-MRS) to quantify responses of total creatine (tCr), glutamate/glutamine (Glx), and lactate across brain regions following a single bout of strenuous exercise. Sixteen healthy adults (nine female, age: 25 ± 3 years) completed ~15 min of cycling, reaching ~85% of predicted heart rate maximum. Single-voxel ¹H-MRS was acquired at 3 Tesla from frontal and visual cortices before (PRE), 15- (POST15), and 30-min (POST30) following exercise. Multivoxel ¹H-MRSI was acquired from frontal and parietal regions PRE and 25-min following exercise (POST25). tCr concentrations decreased by 5.9% in the frontal cortex between PRE and POST15 (6.87 vs. 6.47 mmol·L⁻¹; p < 0.001) and remained significantly lower than PRE at POST30 (6.87 vs. 6.66 mmol·L⁻¹; p = 0.030). Glx concentrations increased by 28.9% in the frontal cortex between PRE and POST15 (6.82 vs. 8.79 mmol·L⁻¹; p = 0.002), returning to baseline by POST30 (p = 0.890). In exploratory analyses (n = 5 after quality control), lactate concentrations increased by 76% in the frontal cortex between PRE and POST15 (0.45 vs. 0.79 mmol·L⁻¹) and remained elevated by 46% at POST30 compared to PRE (0.45 vs. 0.65 mmol·L⁻¹). tCr resonance signals were 5.1% lower across the MRSI grid at POST25 compared with PRE (792.4 vs. 835.4 a.u.; p = 0.001), whereas Glx signals were 11.4% higher at POST25 (1349.8 vs. 1211.4 a.u.; p = 0.003), although region-specific responses were shown. These findings suggest that creatine (Cr) and lactate may serve as alternative energy substrates in response to vigorous exercise, and support Glx as an indicator of excitatory neurotransmission that responds to exercise.

G. Tosini, A.J. Davidson, C. Fukuhara, M. Kasamatsu, and O. Castanon-Cervantes, “Localization of a circadian clock in mammalian photoreceptors,” The FASEB Journal 21 (2007): 3866–3871, https://doi.org/10.1096/fj.07-8371.com.

In Figure 1A and Figure 1B, the representative laser capture microdissection (LCM) micrographs of rat retina were reused and relabeled from LCM of rat retina in Figure 2A and Figure 2B of the author's previous work published in Cell Tissue Res. in 2004 (https://doi.org/10.1007/s00441-003-0822-1). The authors acknowledge that duplicate publication is against The FASEB Journal author guidelines. Due to the age of the paper, the authors were unable to obtain original data but confirm that the representative images used do not affect the conclusions of the paper.

The authors apologize for this error.

Aging is a complex process marked by the gradual functional decline of an organism. It involves imbalances in cellular homeostasis and decreased organ regenerative capacity, causing a significant increase in chronic diseases and mortality. Aging involves a cascade of molecular events such as genomic instability, epigenetic remodeling, and metabolic dysfunction. Targeting key molecular nodes can effectively delay aging and age-related disease progression. Nur77, an NR4A nuclear receptor, is key to stress response, energy sensing, and inflammation regulation. This molecule assists in maintaining stem cell homeostasis, repairing mitochondrial dysfunction, and regulating autophagy and protein quality control, which are core aging events. However, a systematic analysis of the regulatory roles and synergistic effects of Nur77 within the aging network remains lacking. This review comprehensively describes the structure and function of Nur77, explores its role in age-related mechanisms and diseases, and discusses its potential as a diagnostic and therapeutic target. These insights support the development of novel anti-aging strategies based on the Nur77 signaling pathway.