eIF6 modulates skin wound healing by upregulating keratin 6B.

Eukaryotic translation initiation factor 6 (eIF6) plays a crucial role in 60S ribosome biogenesis and protein translation, as well as in hypertrophic scar formation, but its potential role in epithelialization is still poorly understood. Herein, we found that eIF6 negatively correlated with the wound healing process. Mice with genetically knockdown eIF6 (eIF6+/-) showed faster re-epithelization as shown by the longer tongue of the newly formed epidermis. Furthermore, eIF6 ablation accelerated the wound healing process by targeting basal keratinocytes in the eIF6 keratinocyte-conditional knockout (eIF6f/+; Krt5-Cre+) mice. Mechanistically, keratin 6B, an important wound-activated protein, was significantly upregulated in eIF6f/+; Krt5-Cre+ mice skin as proved by RNA-seq, western immunoblots, and immunofluorescence staining. Moreover, an elevated level of KRT6B and accelerated proliferative capacity were also observed in stable knockdown eIF6 HaCaT cells. Taken together, eIF6 downregulation could accelerate epithelialization by upregulating KRT6B expression and promoting keratinocyte proliferation. Our results for the first time indicate that eIF6 might be a novel target to regulate re-epithelialization.

Prognostic value and immunological role of Kruppel-like transcription factor 9 gene in pan-carcinoma.

OBJECTIVE: To investigate the correlation between the expression of Kruppel-like transcription factor 9 (KLF9) and the prognostic value of tumors as well as its relationship with tumor immune invasion. METHODS: A series of bioinformatics methods were used to analyze the relationship between KLF9 and tumor prognosis, tumor mutation burden, microsatellite instability (MSI), and immune cell infiltration in multiple carcinomas. RESULTS: In multiple tumor tissues, the expression of KLF9 was lower compared with paracancerous tissues. Therefore, KLF9 can serve as a protective factor to improve the prognosis of carcinoma patients with certain tumor types. KLF9 was closely related to the clinical staging of various carcinomas. The expression of KLF9 was not only associated with tumor mutation burden and MSI in some tumor types, but also positively correlated with immune and stromal cells in multiple tumors. Further studies have found that, the level of immune cell infiltration was significantly related to the expression of KLF9. CONCLUSION: KLF9 can affect the prognosis of pan-carcinoma, which is related to immune invasion. Therefore, KLF9 can be used as a potential biomarker for the prognosis of pan-carcinoma.

Genome-Wide Analysis Reveals Zinc Transporter ZIP9 Regulated by DNA Methylation Promotes Radiation-Induced Skin Fibrosis via the TGF-ß Signaling Pathway.

Radiation-induced skin fibrosis is a detrimental and chronic disorder that occurs after radiation exposure. DNA methylation has been characterized as an important regulatory mechanism of multiple pathological processes. In this study, we compared the genome-wide DNA methylation status in radiation-induced fibrotic skin and adjacent normal tissues of rats by methylated DNA immunoprecipitation sequencing. Radiation-induced fibrotic skin showed differentially methylated regions associated with 3,650 protein-coding genes, 72 microRNAs, 5,836 long noncoding RNAs and 3 piwi-interacting RNAs. By integrating the mRNA and methylation profiles, the zinc transporter SLC39A9/ZIP9 was investigated in greater detail. The protein level of ZIP9 was increased in irradiated skin tissues of humans, monkeys, and rats, especially in radiogenic fibrotic skin tissues. Radiation induced the demethylation of a CpG dinucleotide in exon 1 of ZIP9 that resulted in recruitment of the transcriptional factor Sp1 and increased ZIP9 expression. Overexpression of ZIP9 resulted in activation of the profibrotic transforming growth factor-ß signaling pathway through protein kinase B in human fibroblasts. In addition, radiation-induced skin fibrosis was associated with increased zinc accumulation. The zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)-1,2-ethylenediamine abrogated ZIP9-induced activation of the transforming growth factor-ß signaling pathway and attenuated radiation-induced skin fibrosis in a rat model. In summary, our findings illustrate epigenetic regulation of ZIP9 and its critical role in promoting radiation-induced skin fibrosis.

[Application of free-style perforator flap for soft tissue defect of knee].

OBJECTIVE: To investigate the effectiveness of free-style perforator flap in repairing the soft tissue defect of knee. METHODS: Between December 2011 and October 2017, 13 patients with the soft tissue defects of knees were repaired with the free-style perforator flaps. There were 9 males and 4 females, with an average age of 40 years (range, 14-65 years). The injuries were caused by traffic accident in 7 cases, crushing in 4 cases, and falling from height in 2 cases. The soft tissue defects in 9 cases formed after 2 weeks-2 months (mean, 1 month) of lower extremity fractures fixation. The other 4 cases were urgently admitted to the hospital after injury, and the time from injury to admission was 0.5-18.0 hours (mean, 8 hours). The size of soft tissue defect ranged from 3 cm×2 cm to 12 cm×8 cm after debridement. Nine propeller flaps, 6 rotating flaps, and 2 V-Y advanced flaps were used; and 9 cases were repaired by single flap and 4 cases were repaired by combined flaps. The size of flap ranged from 7.5 cm×2.5 cm to 20.0 cm×6.0 cm. The donor sites were sutured directly. RESULTS: The flaps survived smoothly and incisions healed by first intention in 12 cases. The congestion occurred in 1 case, which obtained delayed healing after symptomatic treatment. All incisions at donor sites healed by first intention. All patients were followed up 3-24 months with an average of 6 months. The shape and motions of knee were satisfactory. CONCLUSION: The free-style perforator flap can maximize the utilization of the donor area around the knee wound, with reliable blood supply, small trauma, and easy operation. It is an ideal flap for the soft tissue defect of knee.