生物学最新文献

The ability of tumor cells to migrate and invade adjacent tissue is a key property underlying the metastatic process. To ensure greater deformability and to facilitate movement, migratory cells undergo multiple changes in biophysical parameters, including those of stiffness and membrane viscosity. However, reports on correlations between cell motility and stiffness, or between cell motility and membrane microviscosity are rather limited and conflicting. Here, using atomic force microscopy (AFM) and fluorescence lifetime imaging (FLIM), we have investigated alterations in the mechanical properties of cancer cells and in the microviscosity of their plasma membranes that are associated with the migration process. It was found that upon activation of migration either through a "wound healing" test or by inducing epithelial-mesenchymal transition, human colorectal cancer cells undergo profound biomechanical remodeling characterized by simultaneous decreases in cell stiffness and in plasma membrane microviscosity. Our findings, therefore, support the results of previous studies that have shown cell softening and membrane fluidization to be critical adaptive responses enabling cell movement and that these can be regarded as potential biomarkers of tumor cell motility, offering scope for identifying new therapeutic targets.

Autophagy and cellular senescence are fundamental determinants of tumor cell fate. p16^INK4a has emerged as a key regulator at the intersection of these processes, yet its mechanistic role in the autophagy - senescence axis remains incompletely defined. Understanding this interaction is essential for identifying novel therapeutic opportunities in oncology. A systematic literature search was conducted across PubMed, Web of Science, and Scopus for studies published between January 2000 and April 2025, yielding 10 eligible studies after the application of predefined criteria. Evidence shows a dual role of autophagy in tumor biology. In some models, autophagy increased p16^INK4a and senescence-associated β-gal activity, leading to stable growth arrest. Under stress conditions, however, it supported tumor cell survival despite senescence signals. Mechanistically, p16^INK4a acted both upstream, modulating autophagic flux, and downstream, as an effector of autophagy-induced senescence. Study heterogeneity limited direct comparisons. Autophagy and p16^INK4a interact bidirectionally to regulate senescence, representing a critical axis that can shift tumor cells between suppression and survival. Future research should prioritize standardized protocols, longitudinal models, and therapeutic evaluations to clarify whether targeting this pathway can be translated into effective cancer interventions.

Cellular phenotypes are shaped not only by current molecular states but by transient transcriptional programs that encode prior experiences and influence future behavior. Conventional transcriptomic approaches, including bulk and single-cell RNA sequencing, provide high-resolution snapshots of gene expression but are intrinsically destructive, precluding direct linkage between past transcriptional states and downstream cellular fate. In this context, "TimeVault" introduces a fundamentally new paradigm by enabling intracellular storage of endogenous transcriptomes within living cells. By repurposing vault ribonucleoprotein particles to sequester and stabilize polyadenylated mRNA, TimeVault preserves unbiased, transcriptome-wide records of transcriptional states over timescales far exceeding native mRNA half-lives. This capability allows retrospective reconstruction of molecular histories that would otherwise be lost, bridging a critical gap between transient gene expression and long-term phenotypic outcomes. Application of TimeVault to canonical stress responses demonstrates precise temporal gating and durable transcript preservation, while its use in cancer models reveals preexisting transcriptional programs that predict drug-tolerant persister cell formation prior to therapy. These findings highlight the power of molecular memory devices to uncover causal relationships that remain invisible to conventional endpoint analyses. TimeVault establishes intracellular transcriptome archiving as a versatile tool with broad implications for developmental biology, stress adaptation, and therapeutic resistance.

The aim of this investigation was to identify the hub genes associated with ferroptosis in keloid. We analyzed the correlation between differentially expressed genes Yin Yang-1 (YY1) and glutathione peroxidase-4 (GPX4) with keloid by quantitative Real‑Time PCR and Western blot. Molecular biological experiments were conducted to identify the role of YY1 and GPX4 in human keloid fibroblasts (HKFs). glutathione and oxidized glutathione kit, Malondialdehyde Assay Kit and C11-BODIPY (581/591) fluorescence probe were applied to monitor ferroptosis. Gain-of-function and loss-of-function assay demonstrated that YY1 regulated proliferation, migration, fibrosis of HKFs in vitro. YY1 bind to the promoter sequence of target gene GPX4. YY1-induced HKFs ferroptosis was dependent on GPX4 pathway. Furthermore, we discovered that the UCSC Genome Browser Database included an enrichment of H3K27ac signals at the YY1 promoter region. The inhibition of proliferation, migration, fibrosis, and the activation of ferroptosis in knockdown of YY1 HKFs was reversed by EP300 overexpression.

Influenza viruses infect host cells by binding to specific sialic acid receptors present on the surface of target cells, and this receptor binding exhibits specificity depending on cell type and host species. Avian influenza A (H5N1) viruses typically bind preferentially to α2,3-linked sialic acid receptors, although some strains have been reported to acquire binding affinity for the human-type α2,6-linked sialic acid receptors, highlighting the need for ongoing receptor binding analyses of highly pathogenic avian influenza (HPAI) viruses. Notably, in July 2023, two distinct cases of fatal cluster infections in felines caused by HPAI H5N1 viruses were reported for the first time in South Korea (Gwanak and Yongsan). Characterization of the isolated strains revealed high pathogenicity and efficient contact transmission in mammals. In this study, we investigated the receptor binding specificity of the H5N1 viruses associated with these feline outbreaks to assess their potential threat to human health. Our findings demonstrated that both felines-derived and avian-derived H5N1 isolates retained strong binding affinity to avian-type α2,3-linked sialic acid receptors, while showing no detectable binding to human-type α2,6-linked sialic acid receptors. These results provide experimental evidence that the feline H5N1 isolates retain avian-type receptor specificity, indicating a low potential for efficient human-to-human transmission.

Objectives: Chronic kidney disease (CKD) is a global public health concern, characterized by a gradual decline in kidney function, with death of renal tubular epithelial cells (RTECs) as a key pathological mechanism. This study investigated the protective effect of ligustroflavone in CKD and its potential molecular mechanisms.

Methods: In vivo, the unilateral ureteral obstruction (UUO) and folic acid-induced nephropathy (FAN) mouse models were employed to assess the effects of ligustroflavone. In vitro, RTECs were treated with erastin. Western blotting, qRT-PCR, immunofluorescence (IF), and immunohistochemistry (IHC) were performed to detect renal tubular injury both in vivo and in vitro.

Results: In vivo, ligustroflavone treatment significantly improved renal tubular damage and interstitial fibrosis in mice. Furthermore, our results demonstrated that ligustroflavone alleviated ferroptosis of RTECs by inhibiting GSK3β activity and reducing lipid peroxidation in mice. In vitro, ligustroflavone treatment inhibited erastin-induced ferroptosis in RTECs. In addition, ligustroflavone inhibited activation of myofibroblasts induced by ferroptosis of RTECs. Mechanistically, ligustroflavone exerted it's protect effects through the GSK3β/NRF2 pathway by inhibiting GSK3β and activating NRF2, thereby promoting GPX4 expression and suppressing ferroptosis.

Conclusions: In summary, ligustroflavone inhibits ferroptosis in RTECs and confers protection in CKD. These findings suggest that ligustroflavone holds promise as a potential therapeutic agent for CKD.

Since its initial discovery in Swedish pigs in 2009, porcine bocavirus (PBoV) has been detected across Asia, Europe, Africa, and North America. However, the pathogenic potential of PBoV has remained uncertain due to the lack of suitable cell culture systems for viral propagation. In this study, we report the first successful isolation of a Chinese PBoV strain (BK19) from diarrheic piglets in Hunan Province using trypsin-supplemented LLC-PK1 cells. The isolate was characterized through immunofluorescence assay, electron microscopy, plaque formation, and growth kinetics. Whole genome sequencing revealed 43.4-95.7% nucleotide identity with known PBoV strains, with phylogenetic analysis classifying BK19 within the G3 genogroup. Experimental infection of 5-8, 17-19, and 31-33 days old piglets demonstrated age-dependent pathogenicity, with all groups developing characteristic clinical signs including fever, respiratory distress, and diarrhea lasting 3-4 days. Viral shedding peaked in rectal swabs at 4 days post-infection (dpi), with persistent detection through 14 dpi in 5-8 and 17-19 days old groups. Postmortem examination revealed broad tissue tropism in 5-8 and 17-19 days old piglets and age-dependent pathological lesions in intestinal, pulmonary, lymphoid and renal tissues. Immunohistochemical analyses confirmed viral antigen presence in these tissues in 5-8 days old piglets, which correlated with enhanced proliferation of infected cells. These findings provide definitive evidence that PBoV is a primary pathogen in swine, with particular clinical significance for young piglets. This study establishes crucial tools for further research into PBoV biology and control strategies.

In memoriam of Pawel P. Liberski, an enthusiastic scientist of rare intelligence, a loyal and generous friend, and a truly vivid personality.

LeuO, initially identified as a leucine regulator in Escherichia coli, has since been identified as a global regulator required for bacterial pathogenicity in a broad range of bacteria, including Salmonella, Shigella, and Vibrio. This study aimed to determine the regulatory role of LeuO in Salmonella pathogenicity island (SPI)-2, essential for the intracellular proliferation of Salmonella enterica serovar Typhimurium (S. Typhimurium). Overexpression of LeuO repressed the transcription of SPI-2 genes and accordingly decreased its protein levels. Chromatin immunoprecipitation sequencing revealed the genome-wide binding sites of LeuO in S. Typhimurium 14,028 and identified a distinctive 23-nucleotide motif with high similarity to that previously discovered in E. coli. Notably, multiple LeuO-binding sites were predicted within SPI-2, primarily adjacent to the ssrA and ssrB loci. In vitro binding assays verified the high binding affinity between LeuO and three specific motifs located at positions -35 to -12 (ssrA₁),+231 to + 254 (ssrA₂) near ssrA, and at positions -622 to -599 (ssrB₃) near ssrB, relative to their transcription start sites. Furthermore, LeuO overexpression abolished the transcription of lacZ fused to the ssrA promoter containing ssrA₁ and ssrA₂, suggesting the direct repression of ssrA via LeuO-binding. The absence of LeuO increased the intracellular survival of S. Typhimurium within macrophages, whereas its overexpression attenuated bacterial replication, which was presumably associated with the downregulation of SPI-2 by LeuO. This study reveals the versatile regulatory mechanisms of LeuO and underscores its pivotal role in modulating SPI-2 expression, thereby providing key insights into the fine-tuning of virulence by Salmonella during systemic infection.

Tumorigenesis is commonly driven by genetic mutations and disruptions in cellular signalling pathways. Here we show that the oncogenic overexpression of the RNase L inhibitor ABCE1, a component of interferon signalling, leads to distinct and extensive deviations in cancer transcriptomes. RNase L is a cellular endonuclease that cleaves RNA molecules at specific UU and UA dinucleotide sites. Typically, it is activated by viral infections and interferon signalling leading to targeting and destruction of UU/UA-rich viral and cellular mRNA. RNase L has also homoeostatic and tumour suppressive roles. Relying on patient transcriptomic data, we show that ABCE1 is extensively overexpressed in colorectal cancer (CRC) and to a lesser extent in lung cancer. This upregulation was strongly associated with the co-upregulation of almost all UU/UA rich transcripts and downregulation of those that are UU/UA-poor. Many of upregulated mRNAs code for proteins involved in cell cycle regulation and mitosis. Accordingly, the knockdown of ABCE1 in the CRC cell line HT29 led to reduced proliferation. Surprisingly, the very high ABCE1 levels were associated with improved patient survival in CRC. This observation might be related to an anti-ABCE1-specific immune response due to the induction of tumour-reactive cytotoxic T lymphocytes by ABCE1 as previously reported. In lung cancer ABCE1 overexpression is milder and is associated with poor survival. We report a measurable, specific, and extensive modulation of cancer transcriptomes by the oncogenic overexpression of a component of interferon signalling with unexpected outcomes on patient survival.