Effect of highland barley treated with heat-moisture on interactions between gluten and starch granules in dough.

This study aimed to investigate the effect of heat-moisture treatment (HMT)-modified highland barley (HB) on interactions between gluten and starch granules in dough. The results demonstrated that HB addition increased the water absorption, weakened the extensibility, increased the storage modulus (G') and loss modulus (G″), decreased tan δ (G"/G') of dough. The textural and stress relaxation results showed that HB increased the hardness and elastic modulus (E2) of the dough, requiring more stress to compress the dough. Also, the increase in sulfhydryl and surface hydrophobicity all confirmed the addition of HB induced the deterioration of gluten network structure. Furthermore, HMT-HB improved farinograph quality number of flour, decreased tan δ of dough compared with HB. The E2, coefficient of viscosity (η) and hardness increased, while the relaxation time (τ) decreased with increasing HMT strength of HB, suggesting the formation of a tighter dough structure. The secondary structure and microstructure analyses revealed that the HMT could reduce the damage of HB to dough quality. These results indicated that HMT had the potential to enhance the interaction between starch and protein, leading to a denser dough matrix. This study facilitates the basic theory for the comprehensive utilization of HB in the food industry.

Pyrvinium Pamoate Induces Cell Apoptosis and Autophagy in Colorectal Cancer.

BACKGROUND/AIM: In earlier research, we demonstrated that pyrvinium pamoate (PP) can effectively inhibit the proliferation and migration of colorectal cancer (CRC) cells. In the current study, we further explore the possibility of PP, as a potential therapeutic drug in the treatment of CRC. MATERIALS AND METHODS: Hoechst 33258 staining, immunofluorescence, and western blotting were used to further investigate the connection between PP and CRC cell apoptosis and autophagy. RESULTS: We found that PP promoted apoptosis and autophagy of CRC cells. At the protein level, the expression of proteins related to the PI3K/mTOR signaling pathway exhibited a negative correlation with the dosage of PP. PP may therefore induce apoptosis and autophagy by inhibiting the PI3K/mTOR signaling pathway. CONCLUSION: Our in vitro experiments demonstrated that PP could inhibit the progression of colorectal cancer cells by inducing apoptosis and autophagy. The detailed mechanism needs further investigation.

A WGCNA-based cancer-associated fibroblast risk signature in colorectal cancer for prognosis and immunotherapy response.

Background: Cancer-associated fibroblasts (CAFs) are notably involved in colorectal cancer (CRC) tumorigenesis, progression, and treatment failure. In this article, we report the in silico development of a CAF-related prognostic signature for CRC. Methods: We separately downloaded CRC transcription data from The Cancer Genome Atlas and the Gene Expression Omnibus database. Deconvolution algorithms, including Estimating the Proportions of Immune and Cancer Cells and the Microenvironment Cell Population-counter, were used to calculate CAF abundance, while the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression algorithm was used to calculate the stromal score. Weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator algorithm were used to identify CAF-related genes and prognostic signatures. Results: We identified a three-gene, prognostic, CAF-related signature and defined risk groups based on the Riskscores. Multidimensional validations were applied to evaluate the robustness of the signature and its correlation with clinical parameters. We utilized Tumor Immune Dysfunction and Exclusion (TIDE) and oncoPredict algorithms to predict therapy responses and found that patients in low-risk groups are more sensitive to immunotherapy and chemotherapy drugs such as 5-fluorouracil and oxaliplatin. Finally, we used the Cancer Cell Line Encyclopedia and Human Protein Atlas databases to evaluate the mRNA and protein levels encoded by the signature genes. Conclusions: This novel CAF-related three-gene signature is expected to become a potential prognostic biomarker in CRC and predict chemotherapy and immunotherapy responses. It may be of considerable value for studying the tumor microenvironment in CRC.

Alcohol increases treatment failure for Helicobacter pylori eradication in Asian populations.

BACKGROUND AND AIM: Whether alcohol intake is associated with Helicobacter pylori (H. pylori) eradication failure remains controversial, and this meta-analysis was aimed at investigating the effect of alcohol on the risk of H. pylori eradication failure. METHODS: Relevant studies were systematically screened for and retrieved from PubMed and Web of Science (updated to January 2022), and relevant references were manually reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup, publication bias, and sensitivity analyses were also conducted. RESULTS: A total of 40 studies were included in the meta-analysis. No significant association was found between alcohol consumption and the risk of H. pylori eradication failure (OR = 1.09, 95% CI, 0.94-1.26). However, in subgroup analyses stratified by region, a positive association was found in Asian patients (OR = 1.23, 95% CI, 1.03-1.47). In Asian patients, alcohol consumption was associated with the risk of H. pylori eradication failure when the duration of therapy was > 7 days (OR = 1.17, 95% CI, 1.10-1.25), when the treatment regimen included nitroimidazoles (OR = 1.16, 95% CI, 1.09-1.24), and when patients were treated with bismuth-containing quadruple therapy (OR = 1.17, 95% CI, 1.10-1.25). Alcohol intake > 40 g/day was associated with H. pylori eradication failure (OR = 3.17, 95% CI, 1.56-6.41). Moreover, in Asian patients who were administered a vonoprazan (VPZ)-based therapy regimen, alcohol consumption had no effect on H. pylori eradication rates (OR = 1.73, 95% CI, 0.98-3.05). CONCLUSION: Our meta-analysis clearly showed that a higher daily alcohol intake was associated with a higher risk of H. pylori eradication failure in Asian populations. Moreover, a VPZ-based treatment regimen can prevent this effect.

Safety and effectiveness of vonoprazan-based rescue therapy for Helicobacter pylori infection.

BACKGROUND: Vonoprazan (VPZ)-based regimens are an effective first-line therapy for Helicobacter pylori (H. pylori) infection. However, their value as a rescue therapy needs to be explored. AIM: To assess a VPZ-based regimen as H. pylori rescue therapy. METHODS: This prospective, single-center, clinical trial was conducted between January and August 2022. Patients with a history of H. pylori treatment failure were administered 20 mg VPZ twice daily, 750 mg amoxicillin 3 times daily, and 250 mg Saccharomyces boulardii (S. boulardii) twice daily for 14 d (14-d VAS regimen). VPZ and S. boulardii were taken before meals, while amoxicillin was taken after meals. Within 3 d after the end of eradication therapy, all patients were asked to fill in a questionnaire to assess any adverse events they may have experienced. At least 4-6 wk after the end of eradication therapy, eradication success was assessed using a 13C-urea breath test, and factors associated with eradication success were explored. RESULTS: Herein, 103 patients were assessed, and 68 patients were finally included. All included patients had 1-3 previous eradication failures. The overall eradication rates calculated using intention-to-treat and per-protocol analyses were 92.6% (63/68) and 92.3% (60/65), respectively. The eradication rate did not differ with the number of treatment failures (P = 0.433). The rates of clarithromycin, metronidazole, and levofloxacin resistance were 91.3% (21/23), 100.0% (23/23), and 60.9% (14/23), respectively. There were no cases of resistance to tetracycline, amoxicillin, or furazolidone. In 60.9% (14/23) patients, the H. pylori isolate was resistant to all 3 antibiotics (clarithromycin, metronidazole, and levofloxacin); however, eradication was achieved in 92.9% (13/14) patients. All patients showed metronidazole resistance, and had an eradication rate of 91.3% (21/23). The eradication rate was higher among patients without anxiety (96.8%) than among patients with anxiety (60.0%, P = 0.025). No severe adverse events occurred; most adverse events were mild and disappeared without intervention. Good compliance was seen in 95.6% (65/68) patients. Serological examination showed no significant changes in liver and kidney function. CONCLUSION: VAS is a safe and effective rescue therapy, with an acceptable eradication rate (> 90%), regardless of the number of prior treatment failures. Anxiety may be associated with eradication failure.

BMAL1 promotes colorectal cancer cell migration and invasion through ERK- and JNK-dependent c-Myc expression.

BACKGROUND: Cancer metastasis is still a life threat to patients with colorectal cancer (CRC). Brain and muscle ARNT-like protein 1 (BMAL1) is an important biological proteins that can regulate the behavior of cancer cells and their response to chemotherapy. However, the role of BMAL1 in the tumorigenic phenotype of CRC remains unclear. Here, we aim to investigate the functional role and mechanisms of BMAL1 in CRC. METHODS: The mRNA expression of BMAL1 was studied using the Cancer Genome Atlas (TCGA) databases. The protein level in clinical tissues was confirmed by immunohistochemistry (IHC). The effects of BMAL1 on the epithelial-to-mesenchymal transition (EMT) and proliferation of CRC cell lines (including BMAL1 overexpressed or silencing cells) were studied by Transwell, wound healing, CCK-8 and colony formation experiments. A series of experiments were conducted to demonstrate the mechanisms of BMAL1 regulating EMT and cancer proliferation in vitro and in vivo. RESULTS: We found that BMAL1 expression was closely related to the poor prognosis of CRC. BMAL1 overexpression promoted cell proliferation and migration. Mechanistically, we found that BMAL1 may activate the epithelial-to-mesenchymal transition (EMT) pathway and induce the ß-catenin release further promotes the expression of oncogene c-Myc and the migration of colorectal cells by activating MAPK pathway. However, BMAL1 silencing achieved the opposite effect. In addition, blocking MAPK-signaling pathway with specific inhibitors of ERK1/2 and JNK can also downregulate the expressions of c-Myc in vitro. Taken together, these results suggested that the BMAL1/ c-Myc-signaling pathway may regulate the metastasis of CRC through the JNK/ERK1/2 MAPK-dependent pathway. CONCLUSIONS: Our study showed that BMAL1 promotes CRC metastasis through MAPK-c-Myc pathway. These results deepen our understanding of the relationship between BMAL1 and tumorigenic phenotypes, which may become a promising therapeutic target for BMAL1 overexpressing CRC.

Effect of Heat-Moisture Treatment on the Physicochemical Properties, Structure, Morphology, and Starch Digestibility of Highland Barley (Hordeum vulgare L. var. nudum Hook. f) Flour.

This study modified native highland barley (HB) flour by heat-moisture treatment (HMT) at different temperatures (90, 110, and 130 °C) and moisture contents (15%, 25%, and 35%). The effects of the treatment on the pasting, thermal, rheological, structural, and morphological properties of the native and HMT HB flour were evaluated. The results showed that HMT at 90 °C and 25% moisture content induced the highest pasting viscosity (3626-5147 cPa) and final viscosity (3734-5384 cPa). In all conditions HMT increased gelatinization temperature (To, 55.77-73.72 °C; Tp, 60.47-80.69 °C; Tc, 66.16-91.71 °C) but decreased gelatinization enthalpy (6.41-0.43 J/g) in the HMT HB flour compared with that in the native HB flour. The HB flour treated at 15% moisture content had a higher storage modulus and loss modulus than native HB flour, indicating that HMT (moisture content, 15%, 25%, and 35%) favored the strengthening of the HB flour gels. X-ray diffraction and Fourier-transform infrared spectroscopy results showed that HMT HB flour retained the characteristics of an A-type crystal structure with an increased orderly structure of starch, while the relative crystallinity could be increased from 28.52% to 41.32%. The aggregation of starch granules and the denaturation of proteins were observed after HMT, with additional breakage of the starch granule surface as the moisture content increased. HMT could increase the resistant starch content from 24.77% to 33.40%, but it also led to an increase in the rapidly digestible starch content to 85.30% with the increase in moisture content and heating temperature. These results might promote the application of HMT technology in modifying HB flour.

Integrative Proteomic Analysis of Multiple Posttranslational Modifications in Inflammatory Response.

Posttranslational modifications (PTMs) of proteins, particularly acetylation, phosphorylation, and ubiquitination, play critical roles in the host innate immune response. PTMs' dynamic changes and the crosstalk among them are complicated. To build a comprehensive dynamic network of inflammation-related proteins, we integrated data from the whole-cell proteome (WCP), acetylome, phosphoproteome, and ubiquitinome of human and mouse macrophages. Our datasets of acetylation, phosphorylation, and ubiquitination sites helped identify PTM crosstalk within and across proteins involved in the inflammatory response. Stimulation of macrophages by lipopolysaccharide (LPS) resulted in both degradative and non-degradative ubiquitination. Moreover, this study contributes to the interpretation of the roles of known inflammatory molecules and the discovery of novel inflammatory proteins.

Impact of smoking on the eradication of Helicobacter pylori.

BACKGROUND AND AIM: Although the association between the eradication of Helicobacter pylori (H. pylori) and smoking has been confirmed through a meta-analysis, many new studies have reported inconsistent conclusions. An up-to-date meta-analysis based on published relevant studies was conducted in this study to address this issue. METHODS: Eligible studies up to January 2021 were screened and retrieved using PubMed and Web of Science as well as by performing a manual review of references. We calculated the pooled odd ratios (OR) with the 95% confidence interval (CI). Subgroup and sensitivity analyses were also performed. Begg's test was used to determine the publication bias. RESULTS: In total, 39 studies were included in the meta-analysis. The results showed that smoking increases the failure rate of H. pylori eradication treatment (OR = 1.70, 95%CI, 1.49-1.93). The risk of failure also increases with an increase in the smoking dose (>5 cigarettes per day) (OR = 2.59, 95%CI, 1.28-5.24) and the current smoking status (continued to smoke during treatment) (OR = 2.49, 95%CI, 1.52-4.06). Studies with a large proportion of patients with peptic ulcer (OR = 2.14, 95%CI, 1.51-3.02) revealed a higher failure rate among smokers than those with a low proportion of patients with peptic ulcer (OR = 1.57, 95%CI, 1.36-1.81). When vonoprazan (VPZ) was used to treat H. pylori infection, smoking did not affect the eradication rate (OR = 0.94, 95%CI, 0.51-1.75). CONCLUSION: Smoking increases the failure rate of H. pylori eradication treatment. The risk of H. pylori eradication failure in smokers increases with a current smoking status and a high smoking dose. However, when VPZ is used to treat the H. pylori infection, smoking has no effect on the eradication rate.

The changes in pyroptosis-related inflammatory factors in the peripheral blood of patients with Henoch-Schonlein purpura.

BACKGROUND: Henoch-Schonlein purpura (HSP) is a common capillary allergic bleeding disease. To explore the variation of pyroptosis-related inflammatory factors level in the peripheral blood of patients with HSP. METHODS: A total of 87 HSP patients treated in our hospital from June 2020 to March 2021 were selected and divided into the renal impairment group (n=29) and the non-renal impairment group (n=58) according to the presence of hematuria and proteinuria. A total of 50 healthy individuals from the hospital were selected as the control group. The renal impairment and non-renal impairment groups were treated with a regular regimen of compound glycyrrhizin tablets and glucocorticoids, respectively. Serum interleukin (IL)-18, IL-1ß, and peripheral caspase-1-positive cells were compared pre- and post-treatment among the three groups. RESULTS: The pre-treatment serum IL-1ß levels in the renal impairment and non-renal impairment groups were significantly higher than that in the control group (P<0.01). After treatment, the IL-1ß level in the non-renal impairment group was not significantly different from that in the control group (P>0.05). However, the IL-1ß level in the renal impairment group post-treatment was significantly higher than that in the other two groups (P<0.01). The positive rate of caspase-1 expression in peripheral blood before treatment in the renal impairment group and non-renal impairment group was significantly higher than that in the control group (P<0.01). After treatment, the positive rate of caspase-1 expression in the non-renal impairment group was comparable to that in the control group (P>0.05), whereas the rate in the renal impairment group was significantly higher than that in the other two groups (P<0.01). After treatment, the serum IL-1ß levels and caspase-1 positive rate in HSP patients who were responsive to treatment (as assessed by hematuria or proteinuria levels after treatment) were lower than that in patients who were unresponsive to treatment P<0.001), but not significantly different to the control group (P>0.05). CONCLUSIONS: The levels of serum IL-1ß and caspase-1 changed in response to alterations in the disease condition and treatment response in HSP patients, which suggested that pyroptosis-related inflammatory factors may have potential application value in predicting disease progression and efficacy of hormone therapy.

Therapeutic effects of dihydroartemisinin in multiple stages of colitis-associated colorectal cancer.

Colitis-associated colorectal cancer (CAC) develops from chronic intestinal inflammation. Dihydroartemisinin (DHA) is an antimalarial drug exhibiting anti-inflammatory and anti-tumor effects. Nonetheless, the therapeutic effects of DHA on CAC remain unestablished. Methods: Mice were challenged with azoxymethane (AOM) and dextran sulfate sodium (DSS) to establish CAC models. DHA was administered via oral gavage in different stages of CAC models. Colon and tumor tissues were obtained from the AOM/DSS models to investigate inflammatory responses and tumor development. Inflammatory cytokines in the murine models were detected through qRT-PCR and ELISA. Toll-like receptor 4 (TLR4) signaling-related proteins were detected by western blot. Macrophage infiltration was measured using immunostaining analysis, and apoptosis in the colon cancer cells was detected by flow cytometry and western blot. Results: DHA inhibited inflammatory responses in the early stage of the AOM/DSS model and subsequent tumor formation. In the early stage, DHA reversed macrophage infiltration in colon mucosa and decreased the expression of pro-inflammatory cytokines. DHA inhibited the activation of macrophage by suppressing the TLR4 signal pathway. In the late stage of CAC, DHA inhibited tumor growth by enhancing cell cycle arrest and apoptosis in tumor cells. Administration of DHA during the whole period of the AOM/DSS model generated an addictive effect based on the inhibition of inflammation and tumor growth, thereby improving the therapeutic effect of DHA on CAC. Conclusion: Our study indicated that DHA could be a potent agent in managing the initiation and development of CAC without obvious side effects, warranting further clinical translation of DHA for CAC treatment.

A ceRNA-associated risk model predicts the poor prognosis for head and neck squamous cell carcinoma patients.

Head and neck squamous cell carcinoma (HNSCC) is one of the most malignant cancers with poor prognosis worldwide. Emerging evidence indicates that competing endogenous RNAs (ceRNAs) are involved in various diseases, however, the regulatory mechanisms of ceRNAs underlying HNSCC remain unclear. In this study, we retrieved differentially expressed long non-coding RNAs (DElncRNAs), messenger RNAs (DEmRNAs) and microRANs (DEmiRNAs) from The Cancer Genome Atlas database and constructed a ceRNA-based risk model in HNSCC by integrated bioinformatics approaches. Functional enrichment analyses showed that DEmRNAs might be involved in extracellular matrix related biological processes, and protein-protein interaction network further selected out prognostic genes, including MYL1 and ACTN2. Importantly, co-expressed RNAs identified by weighted co-expression gene network analysis constructed the ceRNA networks. Moreover, AC114730.3, AC136375.3, LAT and RYR3 were highly correlated to overall survival of HNSCC by Kaplan-Meier method and univariate Cox regression analysis, which were subsequently implemented multivariate Cox regression analysis to build the risk model. Our study provides a deeper understanding of ceRNAs on the regulatory mechanisms, which will facilitate the expansion of the roles on the ceRNAs in the tumorigenesis, development and treatment of HNSCC.

Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer.

The use of the anthelmintic drug pyrvinium pamoate (PP) in cancer therapy has been extensively investigated in the last decade. PP has been shown to have an inhibitory effect in colorectal cancer (CRC), but the underlying mechanism remains elusive. We aimed to investigate the antitumor activity and mechanisms of PP in CRC. In the present study, we used CCK-8 assays, colony formation assays, and western blotting to reveal that PP effectively suppressed CRC cell proliferation and the AKT-dependent signaling pathway in a concentration-dependent and time-dependent manner. Flow cytometric analysis and fluorescence microscopy demonstrated that PP increased intracellular reactive oxygen species (ROS) accumulation. We found that the inhibitory effect of PP on cell proliferation and AKT protein expression induced by PP could be partially reversed by N-acetyl-L-cysteine (NAC), an ROS scavenger. In addition, the results also demonstrated that PP inhibited cell migration by modulating epithelial-to-mesenchymal transition (EMT)-related proteins, including E-cadherin and vimentin. In conclusion, our data suggested that PP effectively inhibited cell proliferation through the ROS-mediated AKT-dependent signaling pathway in CRC, further providing evidence for the use of PP as an antitumor agent.

Joint Associations of Maternal-Fetal APOL1 Genotypes and Maternal Country of Origin With Preeclampsia Risk.

RATIONALE & OBJECTIVES: Preeclampsia, which disproportionately affects Black women, is a leading cause of preterm delivery and risk for future hypertension and chronic kidney disease (CKD). Apolipoprotein L1 (APOL1) kidney risk alleles, common among Black individuals, contribute substantially to CKD disparities. Given the strong link between preeclampsia and CKD, we investigated whether maternal and fetal APOL1 risk alleles can jointly influence preeclampsia risk, and explored potential modifiers of the association between APOL1 and preeclampsia. STUDY DESIGN: Nested case-control study. SETTING & PARTICIPANTS: 426 Black mother-infant pairs (275 African Americans and 151 Haitians) from the Boston Birth Cohort. EXPOSURE: Maternal and fetal APOL1 risk alleles. OUTCOMES: Preeclampsia. ANALYTICAL APPROACH: Logistic regression models with adjustment for demographic characteristics were applied to analyze associations between fetal and maternal APOL1 risk alleles and risk of preeclampsia and to investigate the effects of modification by maternal country of origin. RESULTS: Fetal APOL1 risk alleles tended to be associated with an increased risk of preeclampsia, which was not statistically significant in the total genotyped population. However, this association was modified by maternal country of origin (P<0.05 for interaction tests): fetal APOL1 risk alleles were significantly associated with an increased risk of preeclampsia among African Americans under recessive (odds ratio [OR], 3.6 [95% CI, 1.3-9.7]; P=0.01) and additive (OR, 1.7 [95% CI, 1.1-2.6]; P=0.01) genetic models but not in Haitian Americans. Also, maternal-fetal genotype discordance at the APOL1 locus was associated with a 2.6-fold higher risk of preeclampsia (P<0.001) in African Americans. LIMITATIONS: Limited sample size in stratified analyses; self-reported maternal country of origin; pre-pregnancy estimated glomerular filtration rate (eGFR) and proteinuria data in mothers were not collected; unmeasured confounding social and/or environmental factors; no replication study. CONCLUSIONS: This study supports the hypothesis that fetal APOL1 kidney risk alleles are associated with increased risk for preeclampsia in a recessive mode of inheritance in African Americans and suggests that maternal-fetal genotype discordance is also associated with this risk. These conclusions underscore the need to better understand maternal-fetal interaction and their genetic and environmental factors as contributors to ethnic disparities in preeclampsia.

Small molecule 2,3-DCPE induces S phase arrest by activating the ATM/ATR-Chk1-Cdc25A signaling pathway in DLD-1 colon cancer cells.

In our previous study, it was reported that 2[[3-(2,3-dichlorophenoxy)propyl]amino]ethanol (2,3-DCPE) induces apoptosis and cell cycle arrest. The current study aimed to investigate the molecular mechanism involved in 2,3-DCPE-induced S phase arrest. The results demonstrated that 2,3-DCPE upregulated phosphorylated (p-)H2A histone family member X, a biomarker of DNA damage, in the DLD-1 colon cancer cell line. Western blotting revealed that 2,3-DCPE increased the checkpoint kinase (Chk)1 (Ser317 and Ser345) level and decreased the expression of M-phase inducer phosphatase 1 (Cdc25A) in a time-dependent manner. Subsequently, the results demonstrated that the ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) inhibitors wortmannin and caffeine had no effect on the cell cycle; however, the inhibitors partially abrogated 2,3-DCPE-induced S phase arrest. Flow cytometry assays revealed that caffeine (2 mM) reduced the proportion of S phase cells from 83 to 39.6% and that wortmannin (500 nM) reduced the proportion of S phase cells from 83 to 48.2%. Furthermore, wortmannin and caffeine inhibited the 2,3-DCPE-mediated phosphorylation of Chk1 and the degradation of Cdc25A. However, these ATM/ATR inhibitors had limited effect on 2,3-DCPE-induced apoptosis. Taken together, the data of the current study indicated that 2,3-DCPE caused DNA damage in colon cancer cells and that 2,3-DCPE-induced S phase arrest was associated with the activation of the ATM/ATR-Chk1-Cdc25A pathway.

Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis.

Clear cell renal cell carcinoma (ccRCC) is a major histological subtype of renal cell carcinoma and can be clinically divided into four stages according to the TNM criteria. Identifying clinical stage-related genes is beneficial for improving the early diagnosis and prognosis of ccRCC. By using bioinformatics analysis, we aim to identify clinical stage-relevant genes that are significantly associated with the development of ccRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided these data into five groups by staging information-normal tissue and ccRCC stages I, II, III, and IV-and eventually identified 500 differentially expressed genes (DEGs). To obtain precise stage-relevant genes, we subsequently applied weighted gene coexpression network analysis (WGCNA) to the GSE73731 dataset and KIRC data from The Cancer Genome Atlas (TCGA). Two modules from each dataset were identified to be related to the tumor TNM stage. Several genes with high inner connection inside the modules were considered hub genes. The intersection results between hub genes of key modules and 500 DEGs revealed UBE2C, BUB1B, RRM2, and TPX2 as highly associated with the stage of ccRCC. In addition, the candidate genes were validated at both the RNA expression level and the protein level. Survival analysis also showed that 4 genes were significantly correlated with overall survival. In conclusion, our study affords a deeper understanding of the molecular mechanisms associated with the development of ccRCC and provides potential biomarkers for early diagnosis and individualized treatment for patients at different stages of ccRCC.

Postoperative carcinoembryonic antigen (CEA) levels predict outcomes after resection of colorectal cancer in patients with normal preoperative CEA levels.

BACKGROUND: Carcinoembryonic antigen (CEA) is a cancer biomarker used in colorectal cancer (CRC) for tumor screening and outcome prediction. However it is still lack of sensitivity and specificity in general population. The present study aimed to investigate the clinical significance of CEA in patients with normal preoperative CEA levels. METHODS: Ninety-four patients were included who received surgery and developed an elevated CEA level postoperatively. They were divided into group A1 and A2 according to the peak CEA level (whether more than 10 ng/mL); group B1 and B2 according to CEA variation (whether reached a normal level at least once). The association between postoperative CEA and overall survival (OS), and disease-free survival (DFS) were analyzed using Kaplan-Meier method and Cox's proportional hazards regression model. RESULTS: The median follow-up time was 38 months. Patients in Group A2 and Group B2 had greater opportunities for recurrence and metastasis (P<0.05) compared to Group A1 and Group B1. Cox regression analysis revealed that high CEA levels and consistently elevated CEA levels were significantly associated with worse OS and DFS. Furthermore, patients with p-stage II in group A2 had worse OS than patients with p-stage III in group A1. The same result was detected when comparing group B2 and B1. CONCLUSIONS: Among patients with an initially normal CEA level, postoperative CEA level and variation could be effective markers for tumor progression assessment. TNM stage, combined with CEA level might be more accurate in prognostic prediction.

Tumor-suppressive function and mechanism of HOXB13 in right-sided colon cancer.

Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in their clinical and molecular features. An investigation of differentially expressed genes (DEGs) between RCC and LCC could contribute to targeted therapy for colon cancer, especially RCC, which has a poor prognosis. Here, we identified HOXB13, which was significantly less expressed in RCC than in LCC and associated with prognosis in RCC, by using 5 datasets from the Gene Expression Omnibus (GEO). Tissue sample analysis showed that HOXB13 was differentially expressed between normal and only RCC tumor tissues. HOXB13 inhibited colon cancer cell proliferation and induced apoptosis both in vitro and in vivo. Furthermore, we found that HOXB13 might be regulated by DNMT3B and suppress C-myc expression to exert antitumor effects via ß-catenin/TCF4 signals in RCC. In conclusion, the current study is the first to demonstrate that HOXB13 has a tumor-suppressive effect in RCC. High expression levels of HOXB13 are associated with prolonged overall survival in patients with RCC. The DNMT3B-HOXB13-C-myc signaling axis might be a molecular target for the treatment of RCC.

Weighted gene coexpression analysis indicates that PLAGL2 and POFUT1 are related to the differential features of proximal and distal colorectal cancer.

In the current era of precision medicine, there is a general consensus that the anatomical site is an important factor in the management of colorectal cancer (CRC). To investigate the underlying molecular mechanisms between proximal and distal CRC and to identify the responsible genes, we analyzed the gene expression patterns of colorectal tumors from two microarray datasets, GSE39582 and GSE14333, on the NCBI Gene Expression Omnibus and the RNA­seq data from TCGA. Weighted coexpression network analysis (WGCNA) was applied to construct a gene coexpression network. The red module in GSE39582 and the dark­gray module from the TCGA dataset were found to be highly correlated with the anatomical site of CRC. A total of 12 hub genes were found in two datasets, 2 of which PLAG1 like zinc finger 2 (PLAGL2) and protein O­fucosyltransferase 1 (POFUT1) were common and upregulated in tumor samples in CRC. The module with the highest correlation provided references that will help to characterize the difference between left­sided and right­sided CRC. The survival analysis of PLAGL2 and POFUT1 expression revealed differences between proximal and distal CRC. Gene set enrichment analysis based on those two genes provided similar results: GPI anchor biosynthesis and peroxisome and selenoamino acid metabolism. PLAGL2 and POFUT1, which have the highest correlation with tumor location, may serve as biomarkers and therapeutic targets for the precise diagnosis and treatment of CRC in the future.

Multidisciplinary evaluation of locally advanced leiomyosarcoma in the lower rectum: a case report and literature review.

Rectal leiomyosarcoma is a rare neoplasm, and no standard therapeutic strategy has been established, other than surgical resection. The prognosis of advanced leiomyosarcoma in the rectum is poor. We describe a case of a 47-year-old man with a locally advanced rectal leiomyosarcoma who presented with anal bleeding and lower abdominal pain. After discussions by a multidisciplinary team (MDT), the patient received preoperative pelvic short-course radiotherapy followed by laparoscopic-assisted abdominoperineal resection. Adjuvant chemotherapy with doxorubicin and ifosfamide was administered postoperatively. Local recurrence was detected 13 months after the resection. The patient received chemotherapy with gemcitabine and docetaxel followed by radioactive particle implantation. Thereafter, apatinib was administered to gain systemic control. The patient died 24 months after the diagnosis. This case report draws attention to treatment with multidisciplinary therapy, as discussed by MDT, for rare locally advanced rectal leiomyosarcoma.