生物学最新文献

Purpose: Neutral cholesterol ester hydrolase 1 (NCEH1), a key enzyme in cellular lipid metabolism, is associated with cancer progression. Its molecular functions in breast cancer remain poorly understood.

Methods: This study evaluated the expression of NCEH1 in breast cancer patients using multiple databases. Functionally, the effects of NCEH1 silencing or overexpression on breast cancer cell growth and motility were investigated. RNA-seq was employed to identify downstream target genes and signalling pathways.

Results: The expression of NCEH1 in breast cancer tissues and cells was significantly higher than that in normal tissues and cells. Silencing NCEH1 suppressed breast cancer cell proliferation and migration. Mechanistically, NCEH1 regulated Neuropilin-1 (NRP1) expression, and both promoted malignant phenotypes in breast cancer by activating the TNF-α/NF-κB signalling pathway.

Conclusion: Our findings demonstrate that NCEH1 accelerates breast cancer progression by modulating NRP1 and activating the TNF-α/NF-κB signalling pathway. Collectively, NCEH1 represents a potential novel biomarker and therapeutic target for breast cancer.

Background: Mitochondria and lysosomes are pivotal in dictating cell survival or death outcomes. While mitochondrial damage and ROS production are key events in mitochondrial cell death, lysosome membrane permeabilization and cathepsin B release mark lysosomal cell death. We aimed to generate a live-cell approach to concurrently monitor mitochondrial redox alterations and lysosomal permeabilization. This would provide mechanistic insight into their dynamic interplay during cell death and enable the discovery of organelle-specific death inducers.

Methods: A dual cell sensor, stably expressing tdTomato-CathepsinB and mitochondria-targeted redox GFP (mt-roGFP), was successfully engineered, and simultaneous imaging of both events by real-time confocal imaging was carried out with selected drugs.

Results: This platform faithfully reported the chronological sequence of organelle-specific events with the progression of cell death, with good temporal and spatial resolution at the single-cell level. Moreover, we have identified and categorised potential lead compounds that predominantly induce lysosomal cell death or mitochondrial cell death, as well as a subset that elicit both events concomitantly.

Conclusion: The study provided evidence that both organelles contribute to cell death in a context-dependent manner, and the temporal analysis of both events is critical in understanding unique organelle-centred cell death.

The emergence and global spread of antimicrobial resistant (AMR) pathogens represent a critical challenge to global public health security. The ESKAPE pathogens refer to a group of highly troublesome multidrug-resistant bacteria responsible for hospital-acquired infections. Of particular concern are Gram-negative ESKAPE pathogens, which pose a significant threat to patient health and healthcare systems worldwide. Systematic investigation into antimicrobial resistance mechanisms and pathogenicity regulation is therefore imperative for developing effective infection control strategies. Emerging evidence highlights small regulatory RNAs (sRNAs) as pivotal post-transcriptional modulators in bacterial physiology, particularly in governing virulence determinant expression and host-pathogen interactions during infection. This review summarizes recent advances in sRNA-mediated regulatory mechanisms in Gram-negative ESKAPE pathogens, with emphasis on Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. We discuss the classification of sRNAs, their regulatory mechanisms, their roles in modulating virulence factors and pathogenicity, as well as the challenges and opportunities in targeting sRNAs for antimicrobial therapy. Evidence accumulated across the studies reviewed indicates that sRNAs exert their function through base pairing with target mRNAs or other sRNA, through interactions with proteins, or as dual-function sRNA. sRNAs have emerged as essential regulators of virulence in the ESKAPE pathogens, influencing capsular polysaccharide production, iron acquisition, biofilm formation, regulation of catabolic pathway genes, cell adhesion and invasion, as well as host immune responses during infection. This review provides a framework for understanding bacterial adaptive evolution through sRNA-mediated regulation and identifies novel intervention targets against multidrug-resistant pathogens.

Gut microbiota has been considered as a key bridge between phytochemicals and host immunity. Prevotella copri (P. copri) showed a close correlation with inflammation, and protocatechuic acid (PCA) has potential protective effects in our previous studies. To understand the underlying mechanism, a total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly assigned into 3 groups, with 6 replicates and 6 piglets per replicate. The piglets were fed a basal diet, a basal diet containing 1.0 × 10⁸ CFU/kg P. copri or 1.0 × 10⁸ CFU/kg P. copri +400 mg/kg PCA for 28 d. Results showed that P. copri decreased the final body weight and average daily gain (ADG), while increased the feed-to-gain ratio (F/G), with increased serum levels of interleukin (IL)-2 and IL-8 in piglets (p < 0.05), and reduced the expression of intestinal tight junction protein (p < 0.05). Dietary supplementation of PCA increased the ADG by suppressing inflammation and enhancing intestinal integrity. In vitro experiments demonstrated that argininosuccinic acid, indole-3-aldehyde, and N-acetylputrescine are critical metabolites produced by P. copri, which initiated inflammatory responses by upregulating pro-inflammatory cytokines and downregulating tight junction proteins in MODE-K cells. PCA was found to effectively attenuate these effects in a dose-dependent manner. In conclusion, PCA can improve the growth performance in weaned piglets by attenuating inflammation caused by P. copri and its metabolites.

The receptor for advanced glycation end products (RAGE) and its ligands are critical drivers of adipose tissue inflammation. While RAGE expression increases in ageing cells and pathological conditions, its specific role in high-fat diet (HFD)-induced adipose tissue senescence remains to be fully elucidated. In this study, we investigated the function of RAGE in the development of adipose tissue senescence associated with obesity. We observed that HFD-fed RAGE-deficient (RAGE^-/-) mice exhibited significantly reduced body weight and adipocyte hypertrophy compared to wild-type (WT) controls. At the molecular level, RAGE^-/- mice displayed lower mRNA expression of cell cycle regulators and markers of the senescence-associated secretory phenotype. This anti-senescent phenotype was accompanied by decreased reactive oxygen species (ROS) production and elevated expression of anti-oxidant genes. Mechanistically, the lack of RAGE resulted in the upregulation of silent information regulator type 1 (SIRT1) in adipose tissues. Notably, the inhibition of SIRT1 reversed these anti-senescent effects and attenuated anti-oxidant gene expression in RAGE-deficient mice. Furthermore, while antioxidant treatment with N-acetylcysteine (NAC) reduced p53 in WT mice, it failed to fully suppress p16 and p21, whereas NAC treatment in RAGE^-/- mice significantly downregulated all senescence markers, suggesting a synergistic protective effect. In conclusion, our results demonstrated that RAGE deficiency improved anti-oxidant properties and prevents adipocyte senescence via the SIRT1 signalling pathway, highlighting a potential therapeutic target for obesity-associated tissue dysfunction.

Novel goose parvovirus (NGPV) infection in ducklings induces short beak and dwarfism syndrome (SBDS), leading to significant economic losses. Since NGPV predominantly infects ducklings, whether reshaping the intestinal flora of ducklings through fecal microbiota transplantation from adult ducks (FMT-A) can alleviate SBDS is an interesting question. This study aimed to investigate the impact of FMT-A on the susceptibility of ducklings to NGPV infection, to elucidate the potential relationship between gut microbiota and viral pathogenicity. The results showed that ducklings were more susceptible to NGPV than adults, and that adult ducks exhibited higher fecal microbiota richness and diversity. FMT-A treatment attenuated NGPV-induced reductions in body weight, beak and tibia length, and muscle mass. Furthermore, FMT-A alleviated gut dysbiosis and intestinal tissue damage, increased glycogen in the intestinal mucosa, upregulated ZO-1 expression, expanded the epiphyseal region, and reduced osteoclast numbers in the tibia of ducklings. Moreover, FMT-A suppressed the expression of the Th17 cell-specific transcription factor retinoic acid receptor-related orphan receptor γt in the ileum and bone, and decreased the expression levels of pro-inflammatory cytokines in the ileum, bone, and serum. These findings indicate that ducklings are more susceptible to NGPV than adult ducks, with significantly lower diversity and abundance of fecal microbiota. FMT-A can stabilize intestinal flora, mitigate intestinal barrier damage, inhibit Th17 cell differentiation, thereby reducing abnormal bone development, and ultimately alleviate SBDS in ducklings. These findings provide a theoretical basis for developing novel strategies targeting gut microbiota modulation to prevent and control SBDS in ducklings.

Recent large-scale outbreaks of diarrhea in pigs in China have been attributed to viral pathogens. To investigate the primary viral causes of diarrhea, we collected 1343 fecal samples from 84 pig farms across 20 provinces. PEDV showed the highest positivity rate at 50.90%, with a positive farm rate of 66.67%. PoRVA had a positive rate of 33.80% and a positive farm rate of 40.48%. TGEV and PDCoV exhibited lower positivity rates of 3.10% and 6.00%, respectively, with positive farm rates of 14.29% and 16.67%. Co-infections, primarily involving PEDV and PoRVA, accounted for 19.05% of cases. Additionally, an analysis of the spatiotemporal distribution of viruses from 2022 to 2024 was conducted. This study also included phylogenetic and amino acid analyses focusing on PEDV and PoRVA. Among them, PEDV predominantly belongs to GIIa and GIIc, while PoRVA predominantly belongs to G4, G5 and G9. We analyzed neutralizing epitopes and functional sites of the PEDV S protein, revealing that the SS2 and SS6 epitopes are relatively conserved, while various mutations were observed in other functional sites. Additionally, significant variability in the VP7 protein of PoRVA was noted among different genotypes, with several conserved amino acid sequences identified, primarily located in the loop regions of the VP7 protein. The study helps identify high-risk areas and peak periods, thereby providing guidance for epidemic early warning and resource allocation. Additionally, the study conducted a further analysis of the antigenic epitopes of PEDV and PoRVA, providing important information for vaccine design and the formulation of immunization strategies.

Uterine fibroids are benign tumors with high incidence and recurrence rates that still pose significant treatment challenges. Traditionally, it has been believed that estrogen and progesterone primarily drive the development and progression of uterine fibroids. Recent studies have revealed that hormonal imbalance can affect reactive oxygen species production and trigger a significant oxidative stress (OS) state. The OS status in uterine fibroids can further amplify the pathological effects caused by hormonal imbalance. This suggests that estrogen, progesterone, and OS may interact to form an estrogen-progesterone-oxidative stress (E-P-OS) network, collectively promoting the progression of uterine fibroids. This network model provides a theoretical basis for the high recurrence rates following hormone monotherapy or surgery. Therefore, we reviewed the molecular mechanisms underlying hormone-OS interactions within the E-P-OS network and elucidated its pathological effects in promoting uterine fibroid progression. The integrated perspective lays the theoretical foundation for developing novel therapies that simultaneously block hormone signaling and counteract oxidative damage. Additionally, we summarized current clinical strategies for hormone therapy and antioxidant treatment, identified potential combination therapy approaches, and explored key challenges in their clinical translation. This aims to provide new directions and evidence for advancing the precision treatment of uterine fibroids.

Staphylococcus aureus (S. aureus) bloodstream infections pose a significant clinical threat, exacerbated by increasing antibiotic resistance and high mortality. While the gut microbiota is recognized as a key modulator of systemic immunity, the mechanisms underlying its protective role against invasive bacterial infections remain incompletely understood. Here, we investigated how gut microbiota influences hepatic immune responses during early S. aureus bloodstream infection using animal models. Our findings demonstrate that the gut microbiota exerts a protective effect against systemic S. aureus infection. Specifically, commensal microbiota-derived signals prime hepatic γδ T cells for rapid interleukin-17A (IL-17A) production upon bacterial challenge. This microbiota-dependent IL-17A response subsequently promotes neutrophil recruitment to the liver, facilitating bacterial clearance and limiting systemic dissemination. Disruption of the gut microbiota impaired hepatic γδ T cell IL-17A production, reduced neutrophil mobilization, and compromised host resistance to infection. Notably, we found that colonization with the commensal Limosilactobacillus reuteri (L. reuteri) activates this hepatic γδT17-neutrophil axis, enhancing host defense against S. aureus as a mechanism involving indole metabolites. This study reveals a novel gut-liver axis whereby intestinal microbiota orchestrates hepatic γδ T cell function to establish an early immunological barrier against invasive bacterial pathogens, offering potential therapeutic avenues for enhancing host defense against life-threatening S. aureus infections.

In recent years, the incidence of gestational diabetes mellitus (GDM) has been steadily increasing, posing risks to the long-term health of both mother and child. We aim to characterize blood glucose levels of pregnant women and predict the risk of GDM during early pregnancy through plasma cell-free mRNA and non-coding RNA (cfRNA). Here, we collected plasma samples from 108 pregnant women (54 with GDM and 54 controls) at around 16 weeks of gestation. Following high-throughput sequencing, we performed differentially abundant genes analysis and evaluated correlations between cfRNA profiles and blood glucose levels. Based on these findings, we developed a predictive model utilizing cf-mRNA and cf-lncRNA signatures. We found that ribosomal genes (RPL/RPS) are decreased in GDM, negatively correlated with 1hGlu and 2hGlu, and enriched in protein synthesis metabolic pathways. Additionally, placental-derived cfRNA contributed less to plasma in GDM, with placental-specific gene IGF2 significantly negatively correlated with blood glucose. Furthermore, 35 blood glucose correlated-cfRNA genes accurately predict GDM, with area under the curve of 0.84 in internal testing and 0.73 in external validation cohort. Our study reveals significant alterations in protein metabolic pathways and placenta-derived RNAs in plasma cfRNA prior to GDM diagnosis.