Correction: Up-Regulation of 91H Promotes Tumor Metastasis and Predicts Poor Prognosis for Patients with Colorectal Cancer.

[This corrects the article DOI: 10.1371/journal.pone.0103022.].

A hypoxia-glycolysis-lactate-related gene signature for prognosis prediction in hepatocellular carcinoma.

BACKGROUND: Liver cancer ranks sixth in incidence and third in mortality globally and hepatocellular carcinoma (HCC) accounts for 90% of it. Hypoxia, glycolysis, and lactate metabolism have been found to regulate the progression of HCC separately. However, there is a lack of studies linking the above three to predict the prognosis of HCC. The present study aimed to identify a hypoxia-glycolysis-lactate-related gene signature for assessing the prognosis of HCC. METHODS: This study collected 510 hypoxia-glycolysis-lactate genes from Molecular Signatures Database (MSigDB) and then classified HCC patients from TCGA-LIHC by analyzing their hypoxia-glycolysis-lactate genes expression. Differentially expressed genes (DEGs) were screened out to construct a gene signature by LASSO-Cox analysis. Univariate and multivariate regression analyses were used to evaluate the independent prognostic value of the gene signature. Analyses of immune infiltration, somatic cell mutations, and correlation heatmap were conducted by "GSVA" R package. Single-cell analysis conducted by "SingleR", "celldex", "Seurat", and "CellCha" R packages revealed how signature genes participated in hypoxia/glycolysis/lactate metabolism and PPI network identified hub genes. RESULTS: We classified HCC patients from TCGA-LIHC into two clusters and screened out DEGs. An 18-genes prognostic signature including CDCA8, CBX2, PDE6A, MED8, DYNC1LI1, PSMD1, EIF5B, GNL2, SEPHS1, CCNJL, SOCS2, LDHA, G6PD, YBX1, RTN3, ADAMTS5, CLEC3B, and UCK2 was built to stratify the risk of HCC. The risk score of the hypoxia-glycolysis-lactate gene signature was further identified as a valuable independent factor for estimating the prognosis of HCC. Then we found that the features of clinical characteristics, immune infiltration, somatic cell mutations, and correlation analysis differed between the high-risk and low-risk groups. Furthermore, single-cell analysis indicated that the signature genes could interact with the ligand-receptors of hepatocytes/fibroblasts/plasma cells to participate in hypoxia/glycolysis/lactate metabolism and PPI network identified potential hub genes in this process: CDCA8, LDHA, YBX1. CONCLUSION: The hypoxia-glycolysis-lactate-related gene signature we built could provide prognostic value for HCC and suggest several hub genes for future HCC studies.

Effect of stability of PTEN on hepatocellular carcinoma.

BACKGROUND: As an antioncogene gene, phosphataseandtensinhomolog (PTEN) is closely related to tumorigenesis. However, after mutation, PTEN will lose its function and no longer exert a tumor suppression effect. Through this research, we explored the impact of PTEN mutation on hepatic carcinoma (HCC) and the mechanism of PTEN for regulating HCC. METHODS: First, bioinformatics was used to analyze the prognosis of PTEN in HCC. PTEN-related genes were then further analyzed by the LinkedOmics database, and GO and KEGG functional enrichment analysis were performed. Next, databases were utilized to predict the mutation and mutation frequency of PTEN. Eventually, CRISPR-Cas12a was applied to detect the R130Q mutation on PTEN in clinical samples of HCC. Finally, the fact that miR-92a-3p targets PTEN was identified by dual luciferase reporter gene assays, RT-qPCR, western blot, and rescue experiments. RESULTS: Bioinformatics analysis indicated the high mutation frequency of R130Q/G/L* site on the PTEN gene. Through CRISPR-Cas12a, R130Q mutation was detected on PTEN in 26 out of 40 clinical samples of HCC. CONCLUSIONS: On the one hand, our study revealed that CRISPR-Cas12a might play an important role in the screening and prognosis of HCC as a new clinical method to detect PTEN mutation.

Hsa_circ_0007990 promotes breast cancer growth via inhibiting YBX1 protein degradation to activate E2F1 transcription.

Breast cancer (BC) is the most commonly diagnosed malignant tumour in females worldwide. Although remarkable advances in early detection and treatment strategies have led to decreased mortality, recurrence and metastasis remain the major causes of cancer death in BC patients. Increasing evidence has demonstrated that circular RNAs (circRNAs) play critical roles in cancer progression. However, the detailed biological functions and molecular mechanisms of circRNAs in BC are unclear. The aim of this study was to investigate the possible role of circRNAs in the progression of BC. Differentially expressed circRNAs in BC were identified by integrating breast tumour-associated somatic CNV data and circRNA high-throughput sequencing. Aberrant hsa_circ_0007990 expression and host gene copy number were detected in BC cell lines via quantitative polymerase chain reaction (qPCR). The expression level of hsa_circ_0007990 in BC tissues was validated by in situ hybridization (ISH). Loss- and gain-of-function experiments were performed in vitro and in vivo, respectively, to explore the potential biological function of hsa_circ_0007990 in BC. The underlying mechanisms of hsa_circ_0007990 were investigated through MS2 RNA pull-down, RNA immunoprecipitation, RNA fluorescence in situ hybridization, immunofluorescence, chromatin immunoprecipitation and luciferase reporter assays. The levels of hsa_circ_0007990 were elevated in BC tissues and cell lines, an effect that was partly due to host gene copy number gains. Functional assays showed that hsa_circ_0007990 promoted BC cell growth. Mechanistically, hsa_circ_0007990 could bind to YBX1 and inhibit its degradation by preventing ubiquitin/proteasome-dependent degradation, thus enhancing the expression of the cell cycle-associated gene E2F1. Rescue experiments suggested that hsa_circ_0007990 promoted BC progression through YBX1. In general, our study demonstrated that hsa_circ_0007990 modulates the ubiquitination and degradation of YBX1 protein and further regulates E2F1 expression to promote BC progression. We explored the possible function and molecular mechanism of hsa_circ_0007990 in BC and identified a novel candidate target for the treatment of BC.

Amphibian-derived peptide RL-RF10 ameliorates paraquat-induced pulmonary fibrosis injury.

Pulmonary fibrosis is the result of dysfunctional repair after lung tissue injury, characterized by fibroblast proliferation and massive extracellular matrix aggregation. Once fibrotic lesions develop, effective treatment is difficult, with few drugs currently available. Here, we identified a short cyclic decapeptide RL-RF10 derived from frog skin secretions as a potential novel lead molecule for the amelioration of pulmonary fibrosis. In vivo experiments indicated that RL-RF10 treatment ameliorated lung histopathological damage and fibrogenesis after paraquat (PQ) induction in a concentration-dependent manner. On day 7, bronchoalveolar lavage fluid assays performed on mice showed that RL-RF10 exerted anti-inflammatory effects by decreasing the expression of inflammation-related factors, including transforming growth factor-ß1 (TGF-ß1) and tumor necrosis factor-α, in lung tissue. In addition, RL-RF10 down-regulated the levels of collagen I, collagen III, and vimentin, while increasing the expression of E-cadherin to inhibit epithelial-mesenchymal transition. Further research demonstrated that the SMAD2/3 signaling pathway, which is strongly linked to TGF-ß1, played a critical function in enhancing the pulmonary fibrosis relief achieved by RL-RF10. Both in vivo and in vitro assays showed that RL-RF10 treatment led to a significant reduction in the phosphorylation levels of SMAD2 and SMAD3 following PQ induction. Overall, we investigated the protective effects and underlying mechanisms of the RL-RF10 peptide against pulmonary fibrosis and demonstrated its potential as a novel therapeutic drug candidate for the treatment of pulmonary fibrotic diseases.

Phenotype and genotype analysis for Helicobacter pylori antibiotic resistance in outpatients: a retrospective study.

To investigate the antibiotic resistance of Helicobacter pylori (H. pylori) in outpatients and to explore the consistency between genotype and phenotype of H. pylori antibiotic resistance. A retrospective study on outpatients screened with urea breath test for H. pylori infection in Nanjing First Hospital from April 2018 to January 2022. Patients who tested positive underwent a consented upper endoscopy, and the H. pylori infection was confirmed by rapid urease test (RUT) and H. pylori culture. For antibiotic resistance phenotype analysis, the H. pylori strains isolated from gastric biopsy were tested for antibiotic resistance phenotype by the Kirby-Bauer disk diffusion test. In addition, the antibiotic resistance genotype of isolated H. pylori was tested with a real-time polymerase chain reaction. A total of 4,399 patients underwent H. pylori infection screening, and 3,306 H. pylori strains were isolated. The antibiotic resistance phenotype test revealed that the resistance rates of metronidazole (MTZ), clarithromycin (CLR), levofloxacin (LEV), amoxicillin (AMX), furazolidone (FR), and tetracycline (TE) were 74.58%, 48.61%, 34.83%, 0.76%, 0.27%, and 0.09%, respectively. Additionally, the antibiotic resistance genotype test revealed that rdxA gene mutation A610G (92.96%), A91G (92.95%), C92A (93.00%), and G392A (95.07%) were predominant in H. pylori with MTZ resistance; 23S rRNA gene mutation A2143G (86.47%) occurred in most H. pylori with CLR resistance; and gyrA gene mutation 87Ile/Lys/Tyr/Arg (97.32%) and 91Asn/Gly/Tyr (90.61%) were the most popular mutations in strains with LEV resistance. The phenotypic resistance and genotypic resistance to CLR (kappa value = 0.824) and LEV (kappa value = 0.895) were in good agreement. The history of eradication with MTZ, CLR, LEV, and AMX was correlated with H. pylori resistance. In short, this study demonstrated that drug resistance of H. pylori was mainly to MTZ, CLR, and LEV in local outpatients. Three drugs can be selected for increased MICs (Minimum Inhibitory Concentration) via single chromosomal mutations. In addition, the genotype could be used to predict the phenotypic H. pylori resistance to CLR and LEV. IMPORTANCE Helicobacter pylori is a key bacterium that causes stomach diseases. There was a high prevalence of H. pylori in the Chinese population. We analyzed the resistance phenotype and genotype characteristics of H. pylori in 4,399 outpatients at the First Hospital of Nanjing, China. We found a higher resistance rate to metronidazole (MTZ) , clarithromycin (CLR), and levofloxacin (LEV), and the genotype could be used to predict the phenotypic H. pylori resistance to CLR and LEV. This study provides information on H. pylori infection and also provides guidance for clinical doctors' drug treatment.

ANGPTL2+cancer-associated fibroblasts and SPP1+macrophages are metastasis accelerators of colorectal cancer.

Background: Liver metastasis (LM) is a leading cause of cancer-related deaths in CRC patients, whereas the associated mechanisms have not yet been fully elucidated. Therefore, it is urgently needed to deeply explore novel metastasis accelerators and therapeutic targets of LM-CRC. Methods: The bulk RNA sequencing data and clinicopathological information of CRC patients were enrolled from the TCGA and GEO databases. The single-cell RNA sequencing (scRNA-seq) datasets of CRC were collected from and analyzed in the Tumor Immune Single-cell Hub (TISCH) database. The infiltration levels of cancer-associated fibroblasts (CAFs) and macrophages in CRC tissues were estimated by multiple immune deconvolution algorithms. The prognostic values of genes were identified by the Kaplan-Meier curve with a log-rank test. GSEA analysis was carried out to annotate the significantly enriched gene sets. The biological functions of cells were experimentally verified. Results: In the present study, hundreds of differentially expressed genes (DEGs) were selected in LM-CRC compared to primary CRC, and these DEGs were significantly associated with the regulation of endopeptidase activity, blood coagulation, and metabolic processes. Then, SPP1, CAV1, ANGPTL2, and COLEC11 were identified as the characteristic DEGs of LM-CRC, and higher expression levels of SPP1 and ANGPTL2 were significantly associated with worse clinical outcomes of CRC patients. In addition, ANGPTL2 and SPP1 mainly distributed in the tumor microenvironment (TME) of CRC tissues. Subsequent scRNA-seq analysis demonstrated that ANGPTL2 and SPP1 were markedly enriched in the CAFs and macrophages of CRC tissues, respectively. Moreover, we identified the significantly enriched gene sets in LM-CRC, especially those in the SPP1+macrophages and ANGPTL2+CAFs, such as the HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION and the HALLMARK_COMPLEMENT. Finally, our in vitro experiments proved that ANGPTL2+CAFs and SPP1+macrophages promote the metastasis of CRC cells. Conclusion: Our study selected four characteristic genes of LM-CRC and identified ANGPTL2+CAFs and SPP1+macrophages subtypes as metastasis accelerators of CRC which provided a potential therapeutic target for LM-CRC.

Peptide RL-QN15 promotes regeneration of epidermal nerve fibers and recovery of sensory function in diabetic skin wounds.

Epidermal nerve fiber regeneration and sensory function are severely impaired in skin wounds of diabetic patients. To date, however, research on post-traumatic nerve regeneration and sensory reconstruction remains scarce, and effective clinical therapeutics are lacking. In the current study, localized treatment with RL-QN15, considered as a drug candidate for intervention in skin wounds in our previous research, accelerated the healing of full-thickness dorsal skin wounds in diabetic mice and footpad skin wounds in diabetic rats. Interestingly, nerve density and axonal plasticity in the skin wounds of diabetic rats and mice, as well as plantar sensitivity in diabetic rats, were markedly enhanced by RL-QN15 treatment. Furthermore, RL-QN15 promoted the proliferation, migration, and axonal length of neuron-like PC12 cells, which was likely associated with activation of the phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway. The therapeutic effects of RL-QN15 were partially reduced by blocking the PI3K/Akt signaling pathway with the inhibitor LY294002. Thus, RL-QN15 showed positive therapeutic effects on the distribution of epidermal nerve fibers and stimulated the recovery of sensory function after cutaneous injury. This study lays a solid foundation for the development of RL-QN15 peptide-based therapeutics against diabetic skin wounds.

Circular RNA circ0104103 inhibits colorectal cancer progression through interactions with HuR and miR-373-5p.

Emerging evidence has suggested that circular RNAs (circRNAs) have vital functions during the initiation and progression of various diseases. However, circRNA potential mechanisms in colorectal cancer (CRC) are largely unknown. Here, we sought to investigate the role and underlying regulatory mechanism of circ0104103 in CRC. circ0104103 was validated by quantitative RT-PCR (qRT-PCR) and Sanger sequencing. Gain- and loss-of-function assays in cell lines and mouse xenograft models were utilized to investigate the effects of circ0104103 in CRC. RNA pull-down assays, RNA immunoprecipitation assays, bioinformatics analyses, RNA FISH, and luciferase reporter assays were used to elucidate the potential mechanism of circ0104103 in CRC. We identified circ0104103, which is strongly downregulated in CRC tissues and cell lines. Functional studies revealed that circ0104103 inhibited CRC cell growth, migration, and invasion both in vitro and in vivo. Mechanistically, circ0104103 binds to HuR, a functional RNA-binding protein commonly expressed in CRC. HuR binds to the 3'UTR of LACTB mRNA to facilitate stabilization and increase its expression. Moreover, circ0104103 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR-373-5p to increase LACTB expression, resulting in inhibiting the occurrence and progression of CRC. Taken together, our study revealed that circ0104103 acts as a tumor suppressor and may be a novel biomarker and therapeutic target in CRC.

Specificity of DNA Vaccines against the Genogroup J and U Infectious Hematopoietic Necrosis Virus Strains Prevalent in China.

Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In addition to the common genogroup J IHNV, genogroup U has been newly discovered in China. However, there is no effective DNA vaccine to fight against this emerging genogroup U IHNV in China. In this study, DNA vaccines encoding the IHNV viral glycoprotein (G) gene of the GS2014 (genogroup J) and BjLL (genogroup U) strains isolated from northern China were successfully developed, which were identified by restriction analysis and IFA. The expression of the Mx-1 gene and G gene in the spleens and muscles of the injection site as well as the titers of the serum antibodies were measured to evaluate the vaccine efficacy by RT-qPCR and ELISA. We found that DNA vaccine immunization could activate Mx1 gene expression and upregulate G gene expression, and the mRNA levels of the Mx1 gene in the muscles were significantly higher than those in the spleens. Notably, DNA vaccine immunization might not promote the serum antibody in fish at the early stage of immunization. Furthermore, the efficacy of the constructed vaccines was tested in intra- and cross-genogroup challenges by a viral challenge in vivo. It seemed that the DNA vaccines were able to provide great immune protection against IHNV infection. In addition, the genogroup J IHNV-G DNA vaccine showed better immune efficacy than the genogroup U IHNV-G or divalent vaccine, which could provide cross-immune protection against the genogroup U IHNV challenge. Therefore, this is the first study to construct an IHNV DNA vaccine using the G gene from an emerging genogroup U IHNV strain in China. The results provide great insight into the advances of new prophylactic strategies to fight both the genogroup J and U IHNV in China.

The Impacts of Iron Overload and Ferroptosis on Intestinal Mucosal Homeostasis and Inflammation.

Intestinal homeostasis is maintained through the interplay of the intestinal mucosa, local and systemic immune factors, and the microbial content of the gut. Iron is a trace mineral in most organisms, including humans, which is essential for growth, systemic metabolism and immune response. Paradoxically, excessive iron intake and/or high iron status can be detrimental to iron metabolism in the intestine and lead to iron overload and ferroptosis-programmed cell death mediated by iron-dependent lipid peroxidation within cell membranes, which contributes to several intestinal diseases. In this review, we comprehensively review recent findings on the impacts of iron overload and ferroptosis on intestinal mucosal homeostasis and inflammation and then present the progress of iron overload and ferroptosis-targeting therapy in intestinal diseases. Understanding the involved mechanisms can provide a new understanding of intestinal disease pathogenesis and facilitate advanced preventive and therapeutic strategies for intestinal dysfunction and diseases.

Reclassifying TNM stage I/II colorectal cancer into two subgroups with different overall survival, tumor microenvironment, and response to immune checkpoint blockade treatment.

Background: The traditional TNM staging system is often insufficient to differentiate the survival discrepancies of colorectal cancer (CRC) patients at TNM stage I/II. Our study aimed to reclassify stage I/II CRC patients into several subgroups with different prognoses and explore their suitable therapeutic methods. Methods: Single-cell RNA (scRNA) sequencing data, bulk RNA sequencing data, and clinicopathological information of CRC patients were enrolled from the TCGA and GEO databases. The tumor microenvironment of CRC tissues was accessed by the ESTIMATE algorithm. The prognostic genes were identified by Cox regression analysis. GO and KEGG analyses were conducted in the DAVID database. GSEA analysis was performed for annotation of the correlated gene sets. Results: We successfully reclassified stage I/II CRC patients into two subgroups and discovered that patients in cluster-2 underwent worse overall survival than those in cluster-1. GSEA analysis showed that immune-associated gene sets were positively enriched in cluster-2. Besides, the differentially expressed genes (DEGs) between cluster-1 and cluster-2 patients also participated in immune-related biological processes and signaling pathways. Moreover, we found that more immune cells infiltrated the microenvironment of cluster-2 patients compared to that of cluster-1 patients, such as Tregs and tumor-associated macrophages. ScRNA sequencing analysis uncovered that most of the enriched immune-associated signaling in cluster-2 patients was mainly attributed to these upregulated immune cells whose infiltration levels were also high in CRC tissues rather than in normal tissues. In addition, we demonstrated that the expression of immune checkpoint genes was significantly higher in cluster-2 patients compared to cluster-1 patients. ScRNA sequencing analysis revealed that the infiltrated CD8+T cells in CRC were naïve T cells and can be activated into effector T cells after immune checkpoint blockade (ICB) treatment. Conclusion: TNM stage I/II CRC patients can be divided into two subgroups, which have different overall survival rates, tumor microenvironment, and response to ICB therapy.

LncRNA SNHG16 promotes colorectal cancer proliferation by regulating ABCB1 expression through sponging miR-214-3p.

Mounting evidence indicates that long non-coding RNAs (lncRNAs) have critical roles in colorectal cancer (CRC) progression, providing many potential diagnostic biomarkers, prognostic biomarkers, and treatment targets. Here, we sought to investigate the role and underlying regulatory mechanism of lncRNA small nucleolar RNA host gene 16 ( SNHG16) in CRC. The expressions of SNHG16 in CRC were identified by RNA-sequencing and quantitative reverse transcription PCR. The functions of SNHG16 were explored by a series of in vitro and in vivo assays (colony formation assay, flow cytometry assay, and xenograft model). Bioinformatics analysis, RNA fluorescence in situ hybridization and luciferase reporter assay were used to investigate the regulatory mechanism of effects of SNHG16. SNHG16 was found to be significantly elevated in human CRC tissues and cell lines. Functional studies suggested that SNHG16 promoted CRC cell growth both in vitro and in vivo. Mechanistically, we identified that SNHG16 is expressed predominantly in the cytoplasm. SNHG16 could interact with miR-214-3p and up-regulated its target ABCB1. This study indicated that SNHG16 plays an oncogenic role in CRC, suggesting it could be a novel biomarker and therapeutic target in CRC.

Amphibian-derived peptide homodimer OA-GL17d promotes skin wound regeneration through the miR-663a/TGF-ß1/Smad axis.

Background: Amphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds. MicroRNAs (miRNAs) are also considered promising targets for the development of effective therapies against skin wounds. However, further research in this field is anticipated. This study aims to identify and provide a new peptide drug candidate, as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing. Methods: A combination of Edman degradation, mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide that was fractionated from the secretion of Odorrana andersonii frog skin using gel-filtration and reversed-phase high-performance liquid chromatography. The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide (PI) double staining against human keratinocytes (HaCaT cells), hemolytic activity against mice blood cells and acute toxicity against mice. The stability of the peptide in plasma was also evaluated. The prohealing potency of the peptide was determined by MTS, scratch healing and a Transwell experiment against HaCaT cells, full-thickness injury wounds and scald wounds in the dorsal skin of mice. miRNA transcriptome sequencing analysis, enzyme-linked immunosorbent assay, real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms. Results: A novel peptide homodimer (named OA-GL17d) that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence 'GLFKWHPRCGEEQSMWT' was identified. Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity, but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice. Mechanistically, OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-ß1 (TGF-ß1) and activate the subsequent TGF-ß1/Smad signaling pathway, thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation. Conclusions: Our results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair. This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.

Susceptibility of Genetic Variations in Methylation Pathway to Gastric Cancer.

Background: DNA methylation in the CpG island is associated with gastric cancer, genetic variations residue in genes involved in methylation pathway could contribute to the occurrence of gastric cancer. Here, we investigated the association between DNMTs (DNMT1/DNMT3A/DNMT3B), MTHFR genetic variations and gastric cancer risk and patients' survival. Patients and Methods: We recruited 490 gastric cancer patients and 488 age- and sex-matched healthy controls. The genotypes of the genetic variations were detected by a Mass-array platform. A commercial Helicobacter pylori (H. pylori) immunogold testing kit was used to determine the H. pylori infection. Results: We found that carriers of DNMT1 rs2228612C allele was associated with decreased gastric cancer risk (CT vs. TT: adjusted OR = 0.70, 95% CI = 0.53-0.94, P = 0.02; CT/CC vs.TT: adjusted OR = 0.73, 95% CI = 0.56-0.96, P = 0.02). Further stratified analysis showed that DNMT1 rs2228612 CT/CC were associated with a decreased gastric cancer risk in the subgroups of age ≤64 years old (adjusted OR = 0.61, 95% CI = 0.41-0.90, P = 0.01), male (adjusted OR = 0.72, 95% CI = 0.53-0.98, P = 0.03), negative H. pylori infection (adjusted OR = 0.67, 95% CI = 0.45-0.98, P = 0.04), tumor stage T3-T4 (adjusted OR = 0.69, 95% CI = 0.51-0.92, P = 0.01), and non-gastric cardiac adenocarcinoma (NGCA) (adjusted OR = 0.72, 95% CI = 0.54-0.97, P = 0.03). However, none of the genetic variations of this study was associated with overall survival. Conclusion: We concluded that the DNMT1 rs2228612C genotype is a protective factor for gastric cancer in Han Chinese population.

Short Hexapeptide Optimized from Rice-Derived Peptide 1 Shows Promising Anti-hyperuricemia Activities.

Plant-derived peptides are a treasure trove for new-generation anti-hyperuricemia drugs. In the current study, we optimized a short hexapeptide rice-derived peptide 1 (RDP1)-M3 (AAAAGA) according to the anti-hyperuricemia RDP1 peptide identified from rice in our previous research. Results showed that RDP1-M3 exerted better hyperuricemia-alleviating and xanthine oxidase (XOD)-inhibiting potency in mice than RDP1. The biodistribution of RDP1-M3 was also analyzed. RDP1-M3 directly decreased XOD and uric acid levels in vivo and in vitro. In addition, RDP1-M3 reduced the expression of urate transporter 1 and glucose transporter 9, increased the level of organic anion transporter 1, reduced the expression of NOD-like receptor superfamily pyrin 3 inflammasomes, and reduced the levels of interleukin-1ß and tumor necrosis factor-α of hyperuricemic mice. Thus, our results indicated that the optimized short hexapeptide RDP1-M3 may be a candidate drug for anti-hyperuricemia.

Retraction Notice to: YTHDF1 Facilitates the Progression of Hepatocellular Carcinoma by Promoting FZD5 mRNA Translation in an m6A-Dependent Manner.

[This retracts the article DOI: 10.1016/j.omtn.2020.09.036.].

A new peptide originated from amphibian skin alleviates the ultraviolet B-induced skin photodamage.

Although amphibian-derived bioactive peptides have attracted increasing attention for their potential use in the treatment of photodamage, research is still in its infancy. In this study, we obtained a new antioxidant peptide, named OA-GI13 (GIWAPWPPRAGLC), from the skin of the odorous frog Odorrana andersonii and determined its effects on ultraviolet B (UVB)-induced skin photodamage as well as its possible molecular mechanisms. Results showed that OA-GI13 directly scavenged free radicals, maintained the viability of hydrogen peroxide-challenged keratinocytes, promoted the release of superoxide dismutase, catalase, and glutathione, and reduced the level of lactate dehydrogenase. Furthermore, topical application of OA-GI13 in mice alleviated dorsal skin erythema and edema and protected the skin against UVB irradiation by increasing antioxidant levels and decreasing peroxide, malondialdehyde, and 8-hydroxydeoxyguanosine levels. OA-GI13 also alleviated oxidative stress injury in vivo and in vitro, possibly by inhibiting p38 protein phosphorylation. Our study confirmed the anti-photodamage effects of this novel amphibian-derived peptide, thus providing a new molecule for the development of drugs and topical agents for the treatment of skin photodamage.