Biological characterization and complete genome analysis of the newly isolated Serratia liquefaciens phage vB_SlqS_ZDD2.

A novel lytic phage named vB_SlqS_ZDD2 was isolated from hospital sewage using the double-layer agar method with Serratia liquefaciens ATCC 27592 as the host. BLASTn analysis showed that the genome sequence of phage vB_SlqS_ZDD2 did not resemble any other phages in the NCBI database. Phenotype and phylogeny analysis indicated that this phage might be a new member of the class Caudoviricetes. Phage vB_SlqS_ZDD2 has a dsDNA genome of 49,178 bp with 55% GC content and has 73 open reading frames. This phage exhibited strong lytic activity and a wide range of pH (3-12) and temperature tolerance (below 70℃).

Interleukin-1ß-Induced Senescence Promotes Osteoblastic Transition of Vascular Smooth Muscle Cells.

INTRODUCTION: Interleukin (IL)-1ß, as a key biomarker and mediator of vascular calcification in patients with end-stage renal disease (ESRD), may be involved in the process of premature senescence of vascular smooth muscle cells (VSMCs). This work sought to investigate whether IL-1ß-induced premature senescence contributes to the process of osteoblastic transition and vascular calcification in VSMCs. METHODS: Eighty-eight patients with ESRD (aged 25-81 years), 11 healthy individuals, and 15 cases of lesion-free distal radial arteries from dialysis ESRD patients with angiostomy were collected in this study. Immunohistochemical analysis was performed to detect expression of IL-1ß, p21, and bone morphogenetic protein-2 (BMP2) in the distal radial arteries. Primary human VSMCs from healthy neonatal umbilical cords were incubated with test agents for 1-3 days. Intracellular levels of reactive oxygen species (ROS) and senescence-associated-ß-galactosidase (SA-ß-gal) staining were used to detect senescent cells. Alizarin red staining and the calcium content of the cell layer were used to detect mineral deposition in VSMCs. RESULTS: Coincident with positive staining of IL-1ß, p21, and BMP2 in the lesion-free distal radial arteries, 66.67% patients showed mineral deposition. Serum IL-1ß was 0.24 ± 0.57, 1.20 ± 2.95, and 9.41 ± 40.52 pg/mL in 11 healthy individuals, 20 patients without calcification, and 53 patients with calcification, respectively. Analysis of the cross-table chi-square test showed cardiovascular calcification is not correlated with levels of serum IL-1ß in patients with ESRD (p = 0.533). In response to IL-1ß, VSMCs showed a senescence-like phenotype, such as flat and enlarged morphology, increased expression of p21, an increased activity of SA-ß-gal, and increased levels of ROS. IL-1ß-induced senescence of VSMCs was required for the activation of IL-1ß/NF-κB/p53/p21 signaling pathway. IL-1ß-induced senescent VSMCs underwent calcification due to osteoblastic transition mainly depending upon the upregulation of BMP2. Resveratrol, an activator of sirtuin-1, postponed the IL-1ß-induced senescence through blocking the NF-κB/p53/p21 pathway and attenuated the osteoblastic transition and calcification in VSMCs. CONCLUSIONS: High levels of IL-1ß in medial smooth muscles of arteries may play roles in inducing senescence-associated calcification. IL-1ß-induced senescence depending on the activation of the NF-κB/p53/p21 signaling pathway and contributing to osteoblastic transition of VSMCs.

Microbial dysbiosis in oral squamous cell carcinoma: A systematic review and meta-analysis.

Objective: The aim of this study was to summarize previously published data and assess the alterations in the composition of the oral microbiome in OSCC using a systematic review and meta-analysis. Design: Electronic databases were systematically searched for studies on the oral microbiome in OSCC published before December 2021. Qualitative assessments of compositional variations at the phylum level were performed. The meta-analysis on abundance changes of bacteria genera was performed via a random-effects model. Results: A total of 18 studies involving 1056 participants were included. They consisted of two categories of studies: 1) case-control studies (n = 9); 2) nine studies that compared the oral microbiome between cancerous tissues and paired paracancerous tissues. At the phylum level, enrichment of Fusobacteria but depletion in Actinobacteria and Firmicutes in the oral microbiome was demonstrated in both categories of studies. At the genus level, Fusobacterium showed an increased abundance in OSCC patients (SMD = 0.65, 95% CI: 0.43-0.87, Z = 5.809, P = 0.000) and in cancerous tissues (SMD = 0.54, 95% CI: 0.36-0.72, Z = 5.785, P = 0.000). The abundance of Streptococcus was decreased in OSCC (SMD = -0.46, 95% CI: -0.88-0.04, Z = -2.146, P = 0.032) and in cancerous tissues (SMD = -0.45, 95% CI: -0.78-0.13, Z = -2.726, P = 0.006). Conclusions: Disturbances in the interactions between enriched Fusobacterium and depleted Streptococcus may participate in or prompt the occurrence and development of OSCC and could be potential biomarkers for detection of OSCC.

A negative feedback loop involving NF-κB/TIR8 regulates IL-1ß-induced epithelial- myofibroblast transdifferentiation in human tubular cells.

Renal tubular epithelial-myofibroblast transdifferentiation (EMT) plays a central role in the development of renal interstitial fibrosis (RIF). The profibrotic cytokine interleukin (IL)-1 and the IL-1 receptor (IL-1R) also participate in RIF development, and Toll/IL-1R 8 (TIR8), a member of the Toll-like receptor superfamily, has been identified as a negative regulator of IL-1R signaling. However, the functions of TIR8 in IL-1-induced RIF remain unknown. Here, human embryonic kidney epithelial cells (HKC) and unilateral ureteric obstruction (UUO)-induced RIF models on SD rats were used to investigate the functions of TIR8 involving IL-1ß-induced EMT. We showed that IL-1ß primarily triggers TIR8 expression by activating nuclear factor-κB (NF-κB) in HKC cells. Conversely, high levels of TIR8 in HKC cells repress IL-1ß-induced NF-κB activation and inhibit IL-1ß-induced EMT. Moreover, in vitro and in vivo findings revealed that TIR8 downregulation facilitated IL-1ß-induced NF-κB activation and contributed to TGF-ß1-mediated EMT in renal tubular epithelial cells. These results suggested that TIR8 exerts a protective role in IL-1ß-mediated EMT and potentially represents a new target for RIF treatment.

The synergistic action of phosphate and interleukin-6 enhances senescence-associated calcification in vascular smooth muscle cells depending on p53.

Cardiovascular calcification is associated with cardiovascular morbidity and mortality of patients with end-stage renal diseases (ESRD). Hyperphosphatemia and many of the inflammatory markers and mediators, including interleukin-6 (IL-6), are considered as the major risk factors of cardiovascular calcification. Although cellular senescence may be involved in cardiovascular calcification caused by phosphate overload and (or) IL-6 in patients with ESRD, less is known about the underlying mechanisms for phosphate- and IL-6-induced senescence-associated calcification of vascular smooth muscle cells (VSMCs). In the present study, we investigated the correlation between cellular senescence and vascular calcification induced by loading phosphate and (or) IL-6 in VSMCs. Our findings show that p53 plays a major role in senescence-associated vascular calcification induced by phosphate overload. IL-6 induces senescence-associated calcification in VSMCs depending upon activation of the IL-6/soluble IL-6 receptor (sIL-6R)/signal transducer and activator of transcription 3 (STAT3)/p53/p21 pathway. We demonstrate that the synergistic action of phosphate overload and IL-6 enhances senescence-associated calcification in a p53-dependent manner and is inhibited by an anti-aging agent (resveratrol) in a dose-dependent manner.