Multifunctional polypeptide-based hydrogel bio-adhesives with pro-healing activities and their working principles.

Wound healing is a complex physiological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Therefore, there is an urgent need for suitable wound dressings for effective and systematical wound management. Polypeptide-based hydrogel bio-adhesives offer unique advantages and are ideal candidates. However, comprehensive reviews on polypeptide-based hydrogel bio-adhesives for wound healing are still lacking. In this review, the physiological mechanisms and evaluation parameters of wound healing were first described in detail. Then, the working principles of hydrogel bio-adhesives were summarized. Recent advances made in multifunctional polypeptide-based hydrogel bio-adhesives involving gelatin, silk fibroin, fibrin, keratin, poly-γ-glutamic acid, ɛ-poly-lysine, serum albumin, and elastin with pro-healing activities in wound healing and tissue repair were reviewed. Finally, the current status, challenges, developments, and future trends of polypeptide-based hydrogel bio-adhesives were discussed, hoping that further developments would be stimulated to meet the growing needs of their clinical applications.

Uterine Tissue Metabonomics Combined with 16S rRNA Gene Sequencing To Analyze the Changes of Gut Microbiota in Mice with Endometritis and the Intervention Effect of Tau Interferon.

Endometritis is a common cow disease characterized by inflammation of endometrium, which leads to infertility or low fertility of cows and brings huge economic losses to the dairy industry. Tau interferon (IFN-τ) has many important biological functions, including an anti-inflammatory effect. The present study aimed to survey the effects of IFN-τ administration on gut microflora and body metabolism in mice with endometritis and to explore the potential relationship. The results indicated that IFN-τ obviously alleviated the damage and ultrastructural changes of mouse endometrium induced by Escherichia coli and enhanced tight junction protein's expression level. Through analysis by 16S rRNA gene sequencing, we found that IFN-τ, especially at 12 h, could regulate the composition of gut microbiota associated with Pediococcus, Staphylococcus, and Enterorhabdus in E. coli-induced mouse endometritis. Through histometabonomics, it was found that endometritis was related to 11 different metabolites and 4 potential metabolic pathways. These metabolites and metabolic pathways were major participants in metabolic pathways, cysteine and methionine metabolism, arachidonic acid metabolism, and pyrimidine metabolism. Correlation analysis of gut microbiota with uterine tissue metabolomics showed that changes in metabolic pathways might be affected by gut microbiota, such as Enterorhabdus in mouse endometritis. The above results indicated that the anti-inflammatory mechanism of IFN-τ might be reduction of the abundance of Enterorhabdus in the gut microbiota, affecting the expression level of important metabolites in uterine tissue and thus playing an anti-inflammatory role. IMPORTANCE The change in intestinal flora has been the focus of many disease studies in recent years, but the pathogenetic effect of interferon on endometritis is still unclear. The results of this study showed that IFN-τ alleviated the damage in mouse endometritis induced by E. coli and improved the endometrial tissue barrier. Its functional mechanism may be reduction of the abundance of Enterorhabdus in the intestinal microbiota, affecting the expression level of important metabolites in uterine tissue and thus playing an anti-inflammatory role.

Interaction between the intestinal flora and the severity of diversion colitis after low anterior resection of rectal cancer.

Background: Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. The colonscopic score is a good tool for differentiating the severity of patients with DC. At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. Methods: Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. Results: In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. Conclusion: After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma.

Circulating lncRNA EGFR-AS1 as a diagnostic biomarker of colorectal cancer and an indicator of tumor burden.

Background: Colorectal cancer (CRC) is one of the most common malignancies. Although CRC treatment has been significantly improved, patient survival remains low because most patients already have advanced disease at diagnosis. Early screening and diagnosis of tumors is critical; however, the current tissue biopsy and radiological evaluation methods have very limited effectiveness. Therefore, establishing new convenient and non-invasive biomarkers is urgently needed for timely detection, therapeutic assessment, and prognostic prediction. At present, non-coding RNAs (ncRNAs) have attracted research attention owing to their potential oncological applications. Methods: The long ncRNA epidermal growth factor receptor antisense RNA 1 (EGFR-AS1) is overexpressed in multiple malignancies including CRC. The present study examined the circulating EGFR-AS1 level in CRC, and the results showed that EGFR-AS1 could be considered an indicator of tumor burden. Results: Elevated circulating EGFR-AS1 levels were detected in CRC cases (n=128) compared with control cases comprising endoscopy confirmed CRC-free individuals [n=64, median expression normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 1.578 vs. 0.780, P<0.001]. Individuals with larger tumors (≥5 cm) had elevated circulating EGFR-AS1 levels compared to those with smaller tumors (<5 cm, 1.739 vs. 1.290, P<0.001). The expression of serum EGFR-AS1 in stage III/IV CRC was higher than that in stage I/II CRC (1.691 vs. 1.412, P<0.05). Plasma EGFR-AS1 levels were markedly reduced following surgical resection of colorectal lesions in a subset of patients [n=32, 1.192 (pre-surgery) vs. 0.692, P<0.001]. Furthermore, the expression of EGFR-AS1 in resected CRC tissues was significantly higher than that in paracancerous tissues (n=32, 1.336 vs. 0.487, P<0.001). Conclusions: These results highlight the potential of EGFR-AS1 as a diagnostic biomarker in CRC.

Sanguinarine Enhances the Integrity of the Blood-Milk Barrier and Inhibits Oxidative Stress in Lipopolysaccharide-Stimulated Mastitis.

Mastitis is a common clinical disease which threatens the welfare and health of dairy cows and causes huge economic losses. Sanguinarine (SG) is a plant-derived alkaloid which has many biological functions, including antibacterial and antioxidant properties. The present study attempted to evaluate the effect of SG on lipopolysaccharide (LPS)-induced oxidative stress reactions and explore its potential mechanisms. The expression profile of SG was analyzed by network pharmacology, and it was found that differentially expressed genes were mainly involved in the Wnt signaling pathway and oxidative stress through GO and KEGG enrichment. In in vitro experiments, the dosage of SG was non-toxic to mouse mammary epithelial cells (mMECs) (p > 0.05). SG not only inhibited the increase in ROS induced by LPS, but also enhanced the activity of antioxidant enzymes (p < 0.05). Moreover, the results of the in vivo experiments showed that SG alleviated LPS-induced inflammatory damage of mouse mammary glands and enhanced the integrity of the blood-milk barrier (p < 0.05). Further studies suggested that SG promoted Nrf2 expression and suppressed the activation of the Wnt signaling pathway (p < 0.05). Conclusively, this study clarified the protective effect of SG on mastitis and provided evidence for new potential mechanisms. SG exerted its antioxidant function through activating Nrf2 and inhibiting the Wnt/ß-catenin pathway, repairing the blood-milk barrier.

Blocking long noncoding RNA MALAT1 restrained the development of laryngeal and hypopharyngeal carcinoma.

PURPOSE: The long non-coding RNA MALAT1 is a predictive marker in several solid tumors with highly conserved sequences. However, the role of non-coding RNA in development of laryngeal or hypopharyngeal cancer remains unclear. METHODS: Tumor tissues and adjacent non-cancer tissues of 24 patients were collected. We detected the expression of MALAT1 in laryngeal cancer tissues and hypopharyngeal cancer tissues. Moreover, we developed a MALAT1 silencing model in human laryngeal tumor cells by transfecting MALAT1 small interfering RNA into human laryngeal carcinoma cell line Hep-2 and pharyngeal carcinoma cell line FaDu with Lipofectamine 2000 system. Cell cycle analysis, Cell Counting Kit-8 assay, Transwell assay, quantitative reverse transcription PCR, and wound-healing assays were performed to evaluate the impact of MALAT1 depletion on laryngeal or hypopharyngeal cancer cell's growth, proliferation, apoptosis, invasion and migration. RESULTS: MALAT1 was significantly up-regulated in laryngeal and hypopharyngeal carcinoma cells. MALAT1 down-regulation induced the increased apoptosis of both cell lines and suppressed cells' proliferation. Cells were arrested in G1/G2 phase and cells of S phase were significantly decreased. Down-regulation of MALAT1 expression can also inhibit the migration and invasion of laryngeal squamous cell carcinoma cell (Hep-2) and hypopharyngeal cancer cell (FaDu). CONCLUSION: In summary, our deactivation model of MALAT1 disentangled the active function of it as a regulator of gene expression governing the hallmarks of laryngeal and hypopharyngeal cancer. Blocking this long non-coding RNA may restrain the development of laryngeal cancer.