Laser hemorrhoidoplasty vs. rubber band ligation: a randomized trial comparing 2 mini-invasive treatment for grade II hemorrhoids.

PURPOSE: As a minimally invasive procedure, laser hemorrhoidoplasty (LHP) can not only relieve the symptoms of hemorrhoids, but also protect the anal cushion structure. This study aimed to investigate the clinical efficacy of LHP in the treatment of grade II hemorrhoids. METHODS: A total of 70 patients with grade II hemorrhoids were randomly assigned to receive LHP or Rubber Band Ligation (RBL) (n = 35 per group) in 2019 from a single center. The postoperative pain, bleeding, feeling of anal distension(local falling, swelling, foreign body sensation, stool) and postoperative recurrence rate were compared between the two groups. RESULTS: The postoperative pain, bleeding, and feeling of anal distension in the LHP group were improved significantly as compared with the RBL group within 2 weeks after surgery (P < 0.01). Both methods can relieve the symptoms of grade II hemorrhoids. There was no difference in the recurrence rate between the two groups at 1 year after surgery (P > 0.05). The patients in LHP group took less time to return to normal activities (P < 0.001). CONCLUSIONS: As a minimally invasive treatment, LHP is easy and not traumatic and results in mild postoperative pain and few complications. It is an ideal choice for grade II hemorrhoids.

Diagnosis and classification of intestinal diseases with urine by surface-enhanced Raman spectroscopy.

Intestinal Disease (ID) is often characterized by clinical symptoms such as malabsorption, intestinal dysfunction, and injury. If treatment is not timely, it will increase the risk of cancer. Early diagnosis of ID is the key to cure it. There are certain limitations of the conventional diagnostic methods, such as low sensitivity and specificity. Therefore, development of a highly sensitive, non-invasive diagnostic method for ID is extremely important. Urine samples are easier to collect and more sensitive to changes in biomolecules than other pathological diagnostic samples such as tissue and blood. In this paper, a diagnostic method of ID with urine by surface-enhanced Raman spectroscopy (SERS) is proposed. A classification model between ID patients and healthy controls (HC) and a classification model between different pathological types of ID (i.e., benign intestinal disease (BID) and colorectal cancer (CRC)) are established. Here, 830 urine samples, including 100 HC, 443 BID, and 287 CRC, were investigated by SERS. The ID/HC classification model was developed by analyzing the SERS spectra of 150 ID and 100 HC, while BID/CRC classification model was built with 300 BID and 150 CRC patients by principal component analysis (PCA)-support vector machines (SVM). The two established models were internally verified by leave-one-out-cross-validation (LOOCV). Finally, the BID/CRC classification model was further evaluated by 143 BID and 137 CRC patients as an external test set. It shows that the accuracy of the classification model validated by the LOOCV for ID/HC and BID/CRC is 86.4% and 85.56%, respectively. And the accuracy of the BID/CRC classification model with external test set is 82.14%. It shows that high accuracy can be achieved with these two established classification models. It indicates that ID patients in the general population can be identified and BID and CRC patients can be further classified with measuring urine by SERS. It shows that the proposed diagnostic method and established classification models provide valuable information for clinicians to early diagnose ID patients and analyze different stages of ID.

Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1.

BACKGROUND: The current study aimed to investigate the molecular mechanism of long non-coding RNA (lncRNA) MEG3 in the development of breast cancer. METHODS: The regulating relationships among lncRNA MEG3, miRNA-330 and CNN1 were predicted by bioinformatics analysis of breast cancer samples in the Cancer Genome Atlas database. The differential expression of lncRNA MEG3, miRNA-330 and CNN1 was first validated in breast cancer tissues and cells. The effects of lncRNA MEG3 on breast cancer malignant properties were evaluated by manipulating its expression in MCF-7 and BT-474 cells. Rescue experiments, dual-luciferase assays, and RNA immunoprecipitation (RIP) experiments were further used to validate the relationships among lncRNA MEG3, miRNA-330 and CNN1. RESULTS: Bioinformatics analysis showed that lncRNA MEGs and CNN1 were significantly downregulated in breast cancer tissues, while miR-330 was upregulated. These differential expressions were further validated in our cohort of breast cancer samples. High expression levels of lncRNA MEG3 and CNN1 as well as low expression of miR-330 were significantly associated with favorable overall survival. Overexpression of lncRNA MEG3 significantly inhibited cell viability, migration and invasion, decreased cells in S stage and promoted cell apoptosis. Dual-luciferase reporter gene assay and RIP experiments showed that lncRNA MEG3 could directly bind to miR-330. Moreover, miR-330 mimics on the basis of lncRNA MEG3 overexpression ameliorated the tumor-suppressing effects of lncRNA MEG3 in breast cancer malignant properties by decreasing CNN1 expression. CONCLUSION: Our study indicated lncRNA MEG3 is a breast cancer suppressor by regulating miR-330/CNN1 axis.

Predictive Role of a Novel Ferroptosis-Related lncRNA Pairs Model in the Prognosis of Papillary Thyroid Carcinoma.

This study aimed to evaluate the potential prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid carcinoma (PTC). Based on The TCGA database, lncRNAs and ferroptosis-related genes with differential expression levels in PTC tumors vs. normal tissues were screened. After the co-expression network construction, ferroptosis-related lncRNAs (FRLs) were screened. Kaplan-Meier analysis was conducted to compare the survival performance of patients with PTC in the high- and low-risk groups. Furthermore, a nomogram was created to enhance PTC prognosis. CIBERSORT was used to investigate the infiltration of various immune cells in high- and low-risk groups. In total, 10 lncRNA pairs with differential expression levels were obtained. There were significant differences in the histological subtype and pathological stage between the high- and low-risk groups, and age (P = 7.39E-13) and FRLM model status (P = 1.09E-04) were identified as independent prognostic factors. Subsequently, the nomogram survival model showed that the predicted one-, three-, and five-year survival rates were similar to the actual one- (c-index = 0.8475), three- (c-index = 0.7964), and five-year (c-index = 0.7555) survival rates. Subjects in the low-risk group had significantly more CD4 + memory T cells and resting myeloid dendritic cells, and subjects in the high-risk group had more plasma B cells and monocytes. The risk assessment model constructed using FRLs showed good predictive value for the prognosis of patients with PTC.

Cancer-associated fibroblasts undergoing neoadjuvant chemotherapy suppress rectal cancer revealed by single-cell and spatial transcriptomics.

Neoadjuvant chemotherapy (NAC) for rectal cancer (RC) shows promising clinical response. The modulation of the tumor microenvironment (TME) by NAC and its association with therapeutic response remain unclear. Here, we use single-cell RNA sequencing and spatial transcriptome sequencing to examine the cell dynamics in 29 patients with RC, who are sampled pairwise before and after treatment. We construct a high-resolution cellular dynamic landscape remodeled by NAC and their associations with therapeutic response. NAC markedly reshapes the populations of cancer-associated fibroblasts (CAFs), which is strongly associated with therapeutic response. The remodeled CAF subsets regulate the TME through spatial recruitment and crosstalk to activate immunity and suppress tumor progression through multiple cytokines, including CXCL12, SLIT2, and DCN. In contrast, the epithelial-mesenchymal transition of malignant cells is upregulated by CAF_FAP through MIR4435-2HG induction, resulting in worse outcomes. Our study demonstrates that NAC inhibits tumor progression and modulates the TME by remodeling CAFs.

Clinical factors of PICC-RVT in cancer patients: a meta-analysis.

PURPOSE: There is a lack of studies that systematically evaluate the clinical factors of PICC-RVT such as treatment, tumor stage, metastasis, and chemotherapy drugs in cancer patients. This study, therefore, aims to evaluate the clinical factors of catheter-related venous thrombosis in cancer patients with indwelling PICC to provide a basis for the clinical prevention and reduction of thrombosis. METHODS: Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Data, and China Biology Medicine disc (CMB)) and searched from their earliest available dates until July 2022. If two or more studies had the same outcome, a meta-analysis using RevMan 5.4.1 was performed. This systematic review was registered at PROSPERO (number CRD42022358426). RESULTS: A total of 19 articles involving 19,824 patients were included for quantitative analysis. Meta-analysis of these studies indicated that a history of chemotherapy, tumor type, tumor stage, presence or absence of metastasis, and use of fluorouracil, etoposide, platinum drugs, and taxane were all risk factors for PICC catheter thrombosis in cancer patients. CONCLUSION: In clinical PICC catheter thrombosis prevention, patients with the above characteristics should be watched more closely than other patients, as they have a higher risk for PICC catheter thrombosis. Based on the present evidence at hand, radiotherapy cannot be considered to be related to the formation of PICC-RVT in cancer patients.

Photo-crosslinking hydrogel for wound healing in a pilonidal sinus patient after open surgery.

Pilonidal sinus is a chronic infectious disease with large incision and high risk of relapse after surgical management. Therefore, effective intervention strategies are urgently needed to reduce the relapse and shorten the wound healing time. Hydrogels have been widely used in regenerative medicine for its great biocompatibility, however, it remains challenging to integrate the material with wound tissues. Here, we reported a case of pilonidal sinus patient using a novel tissue integration material, Photo-crosslinking hydrogel after open surgery. A 38-year-old man with a pilonidal sinus for ˃5 years underwent open surgery. When the surgery was finished, the wound was injected with hydrogel that was irradiated with a ultraviolet light source until covered and solidified completely. Hydrogel needed to be changed 1-2 times per week. We evaluated the healing time as primary outcome and then followed up for ˃1 year to observe the relapse. The wound healed completely in 46 days after open surgery, which was shorter than that reported in other studies. Meanwhile, no recurrence was detected during follow-up. Photo-crosslinking hydrogel effectively promoted wound healing and has the potential to be easily applied in Pilonidal sinus patients after open surgery.

Putative C2H2 Transcription Factor AflZKS3 Regulates Aflatoxin and Pathogenicity in Aspergillus flavus.

Aflatoxin is a carcinogenic secondary metabolite that poses a serious threat to human and animal health. Some C2H2 transcription factors are associated with fungal growth and secondary metabolic regulation. In this study, we characterized the role of AflZKS3, a putative C2H2 transcription factor based on genome annotation, in the growth and aflatoxin biosynthesis of A. flavus and explored its possible mechanisms of action. Surprisingly, the protein was found to be located in the cytoplasm, and gene deletion in A. flavus resulted in defective growth and conidia formation, as well as increased sensitivity to the fluorescent brightener Calcofluor white, Congo red, NaCl, and sorbitol stress. Notably, the biosynthesis of aflatoxin B1 was completely inhibited in the ΔAflZKS3 deletion strain, and its ability to infect peanut and corn seeds was also reduced. RNA sequencing showed that differentially expressed genes in the ΔAflZKS3 strain compared with the control and complementation strains were mainly associated with growth, aflatoxin biosynthesis, and oxidative stress. Thus, AflZKS3 likely contributes to growth, cell development, and aflatoxin synthesis in A. flavus. These findings lay the foundation for a deeper understanding of the roles of C2H2 transcription factors in A. flavus and provide a potential biocontrol target for preventing aflatoxin contamination.

Afper1 contributes to cell development and aflatoxin biosynthesis in Aspergillus flavus.

Aspergillus flavus contaminates crops and produces carcinogenic aflatoxins that pose severe threat to food safety and human health. To identify potential targets to control aflatoxin contamination, we characterized a novel Afper1 protein, which regulates cell development and secondary metabolite biosynthesis in A. flavus. Afper1 is localized in the nucleus and is required for hyphal growth, conidial and sclerotial production, and responses to osmotic stress and essential oils such as cinnamaldehyde and thymol. More importantly, aflatoxin production was impaired in the Afper1 deletion mutant. Proteomics analysis revealed that extracellular hydrolases and proteins involved in conidial development, endoplasmic reticulum (ER) homeostasis, and aflatoxin biosynthesis were differentially regulated in ΔAfper1. Unexpectedly, enzymes participated in reactive oxygen species (ROS) scavenging, including catalase (catA, catB) and superoxide dismutase (sodM) were significantly downregulated, and the ROS accumulation and sensitivity to hydrogen peroxide were confirmed experimentally. Additionally, Afper1 deletion significantly upregulated heterochromatin protein HepA and downregulated acetyltransferases involved in heterochromatin formation. Accompanying ROS accumulation and chromatin remodeling, proteins related to aflatoxins, ustiloxin B and gliotoxin were downregulated. These results implied that Afper1 deletion affected chromatin remodeling and disturbed ER homeostasis, leading to ROS accumulation, and ultimately resulting in defective growth and impaired secondary metabolite biosynthesis.

Lysine 2-hydroxyisobutyrylation orchestrates cell development and aflatoxin biosynthesis in Aspergillus flavus.

Lysine 2-hydroxyisobutyrylation (Khib ) is a recently identified post-translational modification (PTM) that regulates numerous cellular metabolic processes. In pathogenic microorganism, although glycolysis and fungal virulence are regulated by Khib , its potential roles in fungi remain to be elusive. Our preliminary results showed that levels of Khib fluctuate over time in Aspergillus flavus, which frequently contaminates crops and produces carcinogenic aflatoxins. However, the perception of Khib function in A. flavus is limited, especially in mycotoxin-producing strains. Here, we performed a comprehensive analysis of Khib in A. flavus, and 7156 Khib sites were identified in 1473 proteins. Notably, we demonstrated that Khib of AflM, a key enzyme in aflatoxin biosynthesis, affected conidia production and sclerotia formation. Furthermore, aflM deletion impaired aflatoxin biosynthesis, and more importantly, strains in which Khib was mimicked by K to T mutation at K49, K179 and K180 sites showed reduced aflatoxin production compared with wild type and ΔaflM complementation strains. These results indicate that Khib at these sites of AflM negatively regulates aflatoxin biosynthesis in A. flavus. In summary, our study revealed the potential roles of Khib in A. flavus, and particularly shed light on a new way to regulate aflatoxin production via Khib .

Quyu Shengxin Decoction Alleviates DSS-Induced Ulcerative Colitis in Mice by Suppressing RIP1/RIP3/NLRP3 Signalling.

PURPOSE: To study the therapeutic effect of Quyu (QY) Shengxin (SX) decoction (QYSXD) in mice with dextran sulfate sodium- (DSS-) induced ulcerative colitis and to investigate the effects of QYSXD on the regulation of the receptor-interacting protein kinase 1 (RIP1)/receptor-interacting protein kinase 3 (RIP3)/nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3 (NLRP3) signaling pathway. METHOD: Thirty-six mice were randomly divided into the following 6 groups: the experimental group (QYSX group), the model group (DSS group), the positive control group (5-aminosalicylic acid (5-ASA) group), the control group, the first component group (QY group), and the second component group (SX group). Each group included 6 mice. Ulcerative colitis (UC) was induced in the mice by providing 3.5% DSS in drinking water. The mice were weighed every day to evaluate the disease activity index (DAI). After 7 days, the mice were sacrificed, and colonic tissues were obtained for colon length measurement. The morphological changes in the colon and the pathological scores of the mice in each group were observed by hematoxylin-eosin (HE) staining. The messenger ribonucleic acid (mRNA) and protein expression levels of RIP1, RIP3, dynamin-related protein 1 (Drp1), NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1), interleukin (IL)-1ß, and IL-18 in the colon tissues of the mice in each group were detected and compared by real-time quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). The levels of RIP1, RIP3, NLRP3, IL-1ß, and IL-8 in the colonic mucosa were detected by ELISA. Western blotting was used to compare the protein expression of Drp1, caspase-1, mitochondrial fission protein 1 (FIS1), and mitophagy-associated protein light chain 3a/b (LC3a/b) among groups. The levels of reactive oxygen species (ROS) in the colonic mucosal cells were compared by immunofluorescence. RESULTS: Compared with those in the DSS group, the mice with DSS-induced colitis in the QYSX group exhibited clearly higher body weights (P < 0.05) and DAI scores (P < 0.05). The colon lengths of the mice in the QYSX group were longer than those in the DSS group (P < 0.05), and the pathological score of the QYSX group was lower than that of the DSS group (P < 0.05). The RIP1, RIP3, Drp1, IL-1ß, IL-18, and caspase-1 mRNA levels in the QYSX, 5-ASA, SX, and QY groups were significantly lower than those in the DSS group (P < 0.05), but there were no differences between the QYSX group and the 5-ASA group. The levels of RIP1, RIP3, NLRP3, IL-1ß, and IL-18 in the QYSX group were lower than those in the DSS group (P < 0.01). The levels of Drp1, caspase-1, FIS1, and LC3a/b in the QYSX group and the 5-ASA group were lower than those in the DSS group (P < 0.05). The levels of ROS in the colonic mucosal cells in the QYSX, 5-ASA, and QY groups were lower than those in the DSS group (P < 0.05). CONCLUSION: QYSXD has certain therapeutic effects on DSS-induced colitis in mice and may be as effective as 5-ASA. QY and SX decoctions also have certain effects on colitis; however, these decoctions are not as beneficial as QYSXD. QYSXD may ameliorate colitis by inhibiting the expression of RIP1/RIP3/NLRP3 pathway-related proteins and reversing mitochondrial dysfunction to control inflammation.

Discovery and synthesis of rocaglaol derivatives inducing apoptosis in HCT116 cells via suppression of MAPK signaling pathway.

Six rocaglaol derivatives were isolated from Dysoxylum gotadhora, and those compounds showed good cytotoxic activity with IC50 values ranging from 10 to 350 ng/mL against five different cancer cells. Obviously, further total synthesis of rocaglaol derivatives for medical chemistry study is of great significance. Then, twenty six rocaglaol derivatives including 25 new compounds were designed, synthesized, and evaluated for their cytotoxic activities against three human cancer cell lines: human colon cancer cells (HCT116), colorectal cancer stem cells (P6C), and human red leukocyte leukemia cells (HEL), using MTT assay. Most of derivatives showed good cytotoxic activities, with the lowest IC50 being 3.2 nM for HEL cells, which was 169 times stronger than that of the positive control (doxorubicin). Further mechanism study indicated that 11k could significantly suppress MAPK pathway in HCT116 cells, which may responsible for induction of apoptosis and cell cycle arrest.

Efficacy of modified rubber band ligation in the treatment of grade III internal hemorrhoids.

BACKGROUND: Traditional rubber band ligation can improve the symptoms of hemorrhoids, the techniques used vary among centers and the degree of hemorrhoids may also affect the therapeutic efficacy and postoperative outcome, especially for patients with grade III hemorrhoids (hemorrhoid prolapses). This study aimed to investigate the clinical efficacy of modified rubber band ligation (MRBL) in the treatment of grade III internal hemorrhoids. METHODS: A total of 120 patients with grade III internal hemorrhoids were randomly assigned to receive MRBL or Milligan-Morgan haemorrhoidectomy (MMH) (n=60 per group). The post-operative pain, bleeding, urine retention and feeling of anal distension were recorded, and the resting anal pressure (RAP) and post-operative recurrence rate were compared between two groups. RESULTS: The post-operative pain, bleeding and urine retention in the MRBL group were improved significantly as compared with the MMH group (P<0.05), but the feeling of anal distension was similar between them (P>0.05). The RAP remained unchanged after MRBL, but the RAP at 1 month after surgery in the MMH group increased markedly (P<0.01) as compared with that before surgery and was significantly higher than that in the MRBL group (P<0.01). The post-operative recurrence rate was comparable between two groups (P>0.05). CONCLUSIONS: As compared with traditional MMH, MRBL is effective to attenuate the post-operative pain and other discomforts and stabilize the RA. Thus, MRBL is an ideal choice for the treatment of grade III internal hemorrhoids.

Relationship between metformin therapy and risk of colorectal cancer in patients with diabetes mellitus: a meta-analysis.

OBJECTIVE: At present, there are many studies on metformin and the risk of colorectal cancer in patients with diabetes, but the conclusions are contradictory. Our aim is to comprehensively collect the published literature and systematically evaluate the relationship between metformin and the risk of colorectal cancer in patients with diabetes. METHODS: We systematically searched the MEDLINE, EMBASE, and CENTRAL databases up to March 2020. We adopted adjusted estimates and their 95% confidence intervals (CI) to calculate summary effect estimates using either a fixed-effects or a random-effects model. RESULTS: A total of 17 articles were included in this study, with a total of 1,092,074 patients with diabetes. Meta-analysis of observational studies showed that metformin treatment could significantly reduce the incidence of colorectal cancer in diabetic patients (adjusted RR = 0.884, 95%CI = 0.829-0.943), and there was heterogeneity between studies (p = 0.013, I2 = 47.9%). Subgroup analysis showed that metformin treatment was significantly associated with a significantly reduced risk of colorectal cancer in diabetics in America and Europe (adjusted RR = 0.852, 95%CI = 0.786-0.924; adjusted RR = 0.900, 95%CI = 0.845-0.958). Patients with diabetes treated with metformin had a significantly lower risk of colorectal cancer compared with patients who had never been treated with metformin or sulfonamide monotherapy (adjusted RR = 0.863, 95%CI = 0.776-0.960; adjusted RR = 0.911, 95%CI = 0.882-0.941). CONCLUSIONS: Metformin therapy is associated with a significantly reduced risk of colorectal disease in patients with diabetes, and it is necessary to conduct larger, more standardized clinical studies to verify this conclusion.

A novel prognostic model based on multi-omics features predicts the prognosis of colon cancer patients.

BACKGROUND: As a common malignant tumor in the colon, colon cancer (CC) has high incidence and recurrence rates. This study is designed to build a prognostic model for CC. METHODS: The gene expression dataset, microRNA-seq dataset, copy number variation (CNV) dataset, DNA methylation dataset, and transcription factor (TF) dataset of CC were downloaded from UCSC Xena database. Using limma package, the differentially methylated genes (DMGs), and differentially expressed genes (DEGs) and miRNAs (DEMs) were identified. Based on random forest method, prognostic model for each omics dataset were constructed. After the omics features related to prognosis were selected using logrank test, the prognostic model based on multi-omics features was built. Finally, the clinical phenotypes correlated with prognosis were screened using Kaplan-Meier survival analysis, and the nomogram model was established. RESULTS: There were 1625 DEGs, 268 DEMs, and 386 DMGs between the tumor and normal samples. A total of 105, 29, 159, five, and six genes/sites significantly correlated with prognosis were identified in the gene expression dataset (GABRD), miRNA-seq dataset (miR-1271), CNV dataset (RN7SKP247), DNA methylation dataset (cg09170112 methylation site [located in SFSWAP]), and TF dataset (SIX5), respectively. The prognostic model based on multi-omics features was more effective than those based on single omics dataset. The number of lymph nodes, pathologic_M stage, and pathologic_T stage were the clinical phenotypes correlated with prognosis, based on which the nomogram model was constructed. CONCLUSION: The prognostic model based on multi-omics features and the nomogram model might be valuable for the prognostic prediction of CC.

Tanshinone â ¡A inhibits VSMC inflammation and proliferation in vivo and in vitro by downregulating miR-712-5p expression.

The inflammation and proliferation of vascular smooth muscle cells (VSMCs) are the basic pathological feature of proliferative vascular diseases. Tanshinone ⅡA (Tan ⅡA), which is the most abundant fat-soluble element extracted from Salvia miltiorrhiza, has potent protective effects on the cardiovascular system. However, the underlying mechanism is still not fully understood. Here, we show that Tan ⅡA significantly inhibits neointimal formation and decreases VSMC inflammation by upregulating the expression of KLF4 and inhibiting the activation of NFκB signaling. Using a microRNA array analysis, we found that miR-712-5p expression is significantly upregulated in tumor necrosis factor alpha (TNF-α)-treated VSMCs. Loss- and gain-of-function experiments revealed that transfection of miR-712-5p mimic promotes, whereas depletion of miR-712-5p suppresses TNF-α-induced VSMC inflammation, leading to amelioration of intimal hyperplasia induced by carotid artery ligation. Moreover, depletion of miR-712-5p by its antagomir largely abrogates TNF-α-induced VSMC proliferation. Our findings suggest that miR-712-5p mediates the stimulatory effect of TNF-α on VSMC inflammation, and that Tan ⅡA inhibits VSMC inflammation and proliferation in vivo and in vitro by suppression of miR-712-5p expression. Targeting miR-712-5p may be a novel therapeutic strategy to prevent proliferative vascular diseases.

Immune-Related Prognostic Model in Colon Cancer: A Gene Expression-Based Study.

Mounting evidence supports that the malignant phenotypes of cancers are defined not only by the intrinsic activity of tumor cells but also by immune cells that are recruited and activated in tumor-related microenvironment. Here, we developed a diagnostic and prognostic model for colon cancer, based on expression profiles of immune-related genes and immune cell component. As a result, we found that B cell infiltration ratio, CD4+ T cells, as well as immune-related genes of TRIB3, CHGA, CASP7, LGALS4, LEP, NOX4, IL17A, and HSPD1 may be highly relevant with clinical outcome of colon cancer.

A 6 lncRNA-Based Risk Score System for Predicting the Recurrence of Colon Adenocarcinoma Patients.

Colon adenocarcinoma (COAD) is a common type of colon cancer, and post-operative recurrence and metastasis may occur in COAD patients. This study is designed to build a risk score system for COAD patients. The Cancer Genome Atlas (TCGA) dataset of COAD (the training set) was downloaded, and GSE17538 and GSE39582 (the validation sets) from Gene Expression Omnibus database were obtained. The differentially expressed RNAs (DERs) were analyzed by limma package. Using survival package, the independent prognosis-associated long non-coding RNAs (lncRNAs) were selected for constructing risk score system. After the independent clinical prognostic factors were screened out using survival package, a nomogram survival model was constructed using rms package. Furthermore, competitive endogenous RNA (ceRNA) regulatory network and enrichment analyses separately were performed using Cytoscape software and DAVID tool. Totally 404 DERs between recurrence and non-recurrence groups were identified. Based on the six independent prognosis-associated lncRNAs (including H19, KCNJ2-AS1, LINC00899, LINC01503, PRKAG2-AS1, and SRRM2-AS1), the risk score system was constructed. After the independent clinical prognostic factors (Pathologic M, pathologic T, and RS model status) were identified, the nomogram survival model was built. In the ceRNA regulatory network, there were three lncRNAs, four miRNAs, and 77 mRNAs. Additionally, PPAR signaling pathway and hedgehog signaling pathway were enriched for the mRNAs in the ceRNA regulatory network. The risk score system and the nomogram survival model might be used for predicting COAD recurrence. Besides, PPAR signaling pathway and hedgehog signaling pathway might affect the recurrence of COAD patients.

Exogenous pyruvate facilitates ultraviolet B-induced DNA damage repair by promoting H3K9 acetylation in keratinocytes and melanocytes.

Ultraviolet radiation (UVR) is the major cause of numerous skin diseases, including sunburn, skin aging, and skin cancers. Pyruvate is a key intermediate in cellular metabolic pathways, which has shown protective effects against oxidative stress and apoptosis, but its role in UV protection remains unclear. Here we established human and mice in vivo model and found that pyruvate protects both human and mouse skin from UVB-induced DNA damage. Moreover, assays in primary keratinocytes and melanocytes further supported the protective role of exogenous pyruvate against UVB-induced DNA damage. Mechanically, pyruvate stimulates the activation of Histone H3 Lysine 9 (H3K9) acetylation, which is an essential step for nucleotide excision repair (NER) pathway. In conclusion, our results suggest that treatment of pyruvate might be an effective strategy to prevent UVB-induced skin diseases.

Association of a novel seven-gene expression signature with the disease prognosis in colon cancer patients.

Older patients who are diagnosed with colon cancer face unique challenges, specifically regarding to cancer treatment. The aim of this study was to identify prognostic signatures to predicting prognosis in colon cancer patients through a detailed transcriptomic analysis. RNA-seq expression profile, miRNA expression profile, and clinical phenotype information of all the samples of TCGA colon adenocarcinoma were downloaded and differentially expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEMis) were identified. A competing endogenous RNA (ceRNA) network was constructed further and DEMs related with prognosis in the ceRNA network was screened using Cox regression analysis. Risk score models for predicting the prognosis of colon cancer patients were built using these DEMs. A total of 1476 DEMs, 9 DELs, and 243 DEMis between the tumor and normal samples were identified and functional enrichment analyses showed that the DEMs were significantly enriched in the nervous system development, ribosome biogenesis pathways in eukaryotes, and drug metabolism cytochrome P450. Twelve DEMs related with prognosis were screened from the ceRNA network. Thereafter, the risk score models of prognostic DEMs were obtained, involving seven DEMs (SGCG, CLDN23, SLC4A4, CCDC78, SLC17A7, OTOP3, and SMPDL3A). Additionally, cancer stage was identified as a prognostic clinical factor. This prognostic signature was further validated in two independent datasets. Our study developed a seven-mRNA and one-clinical factor signature that are associated with prognosis in colon cancer patients, which may serve as possible biomarkers and therapeutic targets in the future.