The FASEB Journal最新文献

Parasites can induce changes in their hosts, favoring the success of the infection and its development at each stage of their life cycle. The host minimizes the effects of the parasite's presence through its defense system, balancing the parasite–host relationship. The intricate parasite–host relationship provides physiological, immunological, and molecular cues that suggest interaction and mutual regulation of the transcriptome and epigenome, promoting phenotypic plasticity and survival in a changing environment. There has been a growing interest in the epigenetic mechanisms of Schistosoma mansoni, a parasite with remarkable phenotypic plasticity in response to signals from the environment and its hosts. Several studies emphasize the epigenetic mechanisms behind the phenotypic plasticity of Schistosoma. Regarding the host's gene expression in the face of infection, however, there is little evidence of which pathways are altered by the passage of the parasite through the lungs and by the pathogenesis in the hepatic portal system. In this work, we characterized S. mansoni infection in parasitological and biochemical aspects of the murine model in comparison with the profile of the initial, acute, and chronic phases of infection (3, 7, and 20 wpi (weeks postinfection), respectively). The biochemical and morphological results of the infection at 3, 7, and 20 wpi show the phenotypic changes of schistosomiasis in the murine model. ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) at 7 wpi shows a chromatin with higher accessibility for infected individuals, and Western blotting at 7 wpi shows an increase in histone marks H3K9ac and H3K9me3, indicating a change in chromatin status after infection. RNA-seq (RNA sequencing) for 7 wpi results show a differential profile of lipid metabolism genes that are negatively modulated, while immune system genes are positively modulated. It is interesting to note that the negative modulation of mRNA expression of lipid pathway genes causes the rates of these metabolites to appear decreased in the blood, while the increased expression of immune system defense genes is in accordance with liver histology data, which shows an inflammatory profile.

Although extensive clinical and basic research has been conducted on diabetic cardiomyopathy (DbCM), the therapeutic efficacy for this condition remains significantly limited. Ubiquitin-specific peptidase 20 (USP20), a deubiquitinating enzyme, plays an essential role in regulating protein ubiquitination and modulating various cellular processes. In this study, we aimed to investigate the effect of USP20 on the pathogenesis of DbCM, which may provide a novel therapeutic target for its treatment. The cardiomyocyte-specific USP20 conditional knockout (USP20CKO) mice were employed in this study. The type 2 diabetes mouse model was established using db/db leptin receptor–deficient mice and high-fat diet/streptozotocin–induced mice. USP20 expression was downregulated in the myocardium of diabetic mice. Cardiomyocyte-specific USP20 deficiency aggravated cardiac remodeling and myocardial dysfunction in diabetic mice. LC–MS/MS analysis, along with Co-IP results, demonstrated the interaction between stimulator of interferon genes (STING) and USP20. In mechanism, USP20 directly binds to STING and promotes its degradation through the autophagy pathway by deubiquitinating p62 via its active site C154, thereby alleviating the myocardial inflammation and improving ventricular remodeling and heart failure induced by diabetes.

Sepsis is a heterogeneous syndrome characterized by a dysregulated host response to infection resulting in life-threatening organ dysfunction. It has emerged as one of the most critical causes of mortality worldwide, imposing not only substantial physical and economic burdens on patients and their families but also creating a significant strain on healthcare systems worldwide. Despite its severity, the absence of targeted effective therapeutics remains a disappointing and persistent challenge in clinical management. This underscores the urgent need to develop a more comprehensive understanding of sepsis and to elucidate its underlying pathophysiological mechanisms, which is essential for identifying novel therapeutic strategies. In this review, we synthesize recent advances in sepsis subphenotypes, diagnostic criteria, and associated complications, with particular emphasis on alterations in the host immune response. This includes an analysis of the functional states of key immune cells and the dynamic interplay between the host and gut microbiota. Furthermore, we discuss future directions and potential innovative treatments for sepsis. It is anticipated that this comprehensive overview may provide new perspectives and avenues for improving the prognosis and management of sepsis.

Nociceptive afferent neurons within the dorsal root ganglion (DRG) detect and relay painful peripheral stimuli, and the malfunctioning of this process leads to sustained pain states. Animal model studies have been invaluable for demonstrating the importance of the DRG nociceptor in pain sensation and the development of related analgesic targets. However, a human in vitro model of nociception is essential to confirming the relevance of preclinical findings for therapeutic drug development. We characterized the nociceptive properties of differentiated cells from the human DRG-derived immortalized cell line HD10.6 and developed their use into an in vitro model of human nociceptive signaling and therapy. Within differentiated HD10.6 cells, we confirmed the abundance and function of machinery linked with pain sensation, including key ion channels (TRPV1, NaV1.7) and afferent peptides (CGRP, Substance P), by immunofluorescence and calcium influx assays. Through whole-cell patch clamp, including current clamp and voltage clamp, we recorded the baseline electrophysiological parameters of differentiated HD10.6 cells. We further found that differentiated HD10.6 cells express the mu opioid receptor 1 protein, and that mu agonist DAMGO blocks depolarization-evoked calcium influx in a naloxone-reversible fashion. Importantly, excitation and peripheral sensitization were induced within HD10.6 cells in response to an inflammatory cocktail, mirroring nociceptors in a pain state during and after tissue damage or inflammation. HD10.6 cells were also cultured into dual-chambered microfluidic devices to mirror the physiological anatomy of the nociceptor. Within this system, genetic therapy adeno-associated-virus was successfully taken up by the peripheral terminals and transported to the soma.

Major congenital malformations are common, and most cases have no known etiology because of complex interactions between genetic and environmental factors and variable phenotypic outcomes. Congenital NAD Deficiency Disorder (CNDD), a cause of multiple congenital malformations and embryo loss, exemplifies this variability in phenotypic presentation, even between siblings with the same underlying genetic variants. Mouse models show that CNDD is caused by embryonic nicotinamide adenine dinucleotide (NAD) deficiency because of the embryos' genetic inability to synthesize NAD and/or insufficient maternal provision of NAD precursors to embryos. But it is unknown when during pregnancy embryos become susceptible to developing malformations and what drives the malformation variability. Here, we induced CNDD in wild-type mice via the maternal diet and longitudinally tracked affected and unaffected embryos in utero. We compared 3-day interval measurements of the maternal blood NAD metabolome with embryo phenotype using Fast Spin Echo Magnetic Resonance Imaging, mass spectrometry, and micro-computed tomography. Malformations varied between litters, but they correlated with different embryo growth dynamics. Mice with lower maternal NAD Salvage Pathway metabolite levels and minimal levels of derived excretion metabolites from embryonic day 6.5 onward had smaller embryos with more malformations. This showed that altered embryo growth and reduced maternal NAD precursor availability during organogenesis resulted in CNDD. Variability in the timing of maternal metabolic perturbation corresponded to variability in organ and tissue defect types between litters. As embryo phenotypes are directly linked to maternal NAD precursor availability prior to and during organogenesis, this suggests NAD-derived metabolites are potential biomarkers predicting CNDD.

C. Shi, L. Li, X. L. Sun, S. Liu, and Y. Zhou, “Polystyrene Microplastics Disrupt Vertical Transmission of the Breast Milk Microbiome, Impairing Early-Life Gut Colonization and Immune Development in Offspring,” The FASEB Journal 40, no. 1 (2026): e71448, https://doi.org/10.1096/fj.202503819R.

In the original article, the author name “Shen Liu” was misspelled in the author byline and the “Author Contributions.” The author's name should read “Sheng Liu.”

The correct author list is:

Chenxi Shi, Lianen Li, Xian Liang Sun, Sheng Liu, Yitong Zhou.

We apologize for this error.