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Abstract Purpose To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients. Materials and methods The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data. Results All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration. Conclusion RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.

ABSTRACTRectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as – the PI3K/AKT pathway, Wnt/β-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.

Abstract Background While previous studies have indicated variability in distant metastatic potential among different mismatch repair (MMR) states in colorectal cancer (CRC), their findings remain inconclusive, especially considering potential differences across various ethnic backgrounds. Furthermore, the gene regulatory networks and the underlying mechanisms responsible for these variances in metastatic potential across MMR states have yet to be elucidated. Methods We collected 2058 consecutive primary CRC samples from the South West of China and assessed the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemistry. To explore the inconsistencies between different MMR statuses and recurrence, we performed a meta‐analysis. To delve deeper, we employed Weighted Gene Co‐expression Network Analysis (WGCNA), ClueGo, and iRegulon, pinpointing gene expression networks and key regulatory molecules linked to metastasis and recurrence in CRC. Lastly, both univariate and multivariate Cox regression analyses were applied to determine the impact of core regulatory molecules on metastasis. Results Of the samples, 8.2% displayed deficient MMR (dMMR), with losses of MLH1 and PSM2 observed in 40.8% and 63.9%, respectively. A unique 24.3% isolated loss of PMS2 without concurrent metastasis was identified, a result that diverges from established literature. Additionally, our meta‐analysis further solidifies the reduced recurrence likelihood in dMMR CRC samples compared to proficient MMR (pMMR). Two gene expression networks tied to distant metastasis and recurrence were identified, with a majority of metastasis‐related genes located on chromosomes 8 and 18. An IRF1 positive feedback loop was discerned in the metastasis‐related network, and IRF1 was identified as a predictive marker for both recurrence‐free and distant metastasis‐free survival across multiple datasets. Conclusion Geographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis.

Abstract Background Cancer biomarkers play a pivotal role in the diagnosis, prognosis, and treatment response prediction of the disease. In this study, we analyzed the expression levels of RhoB and DNp73 proteins in rectal cancer, as captured in immunohistochemical images, to predict the 5‐year survival time of two patient groups: one with preoperative radiotherapy and one without. Methods The utilization of deep convolutional neural networks in medical research, particularly in clinical cancer studies, has been gaining substantial attention. This success primarily stems from their ability to extract intricate image features that prove invaluable in machine learning. Another innovative method for extracting features at multiple levels is the wavelet‐scattering network. Our study combines the strengths of these two convolution‐based approaches to robustly extract image features related to protein expression. Results The efficacy of our approach was evaluated across various tissue types, including tumor, biopsy, metastasis, and adjacent normal tissue. Statistical assessments demonstrated exceptional performance across a range of metrics, including prediction accuracy, classification accuracy, precision, and the area under the receiver operating characteristic curve. Conclusion These results underscore the potential of dual convolutional learning to assist clinical researchers in the timely validation and discovery of cancer biomarkers.

Biomass-based alternatives for the manufacturing of bioplastic materials are important aspects of a more sustainable future; their physicochemical properties need to be able to compete with the existing market to establish them as a viable alternative [...]

Abstract The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.

Aim: The process of biomarker discovery is being accelerated with the application of artificial intelligence (AI), including machine learning. Biomarkers of diseases are useful because they are indicators of pathogenesis or measures of responses to therapeutic treatments, and therefore, play a key role in new drug development. Proteins are among the candidates for biomarkers of rectal cancer, which need to be explored using state-of-the-art AI to be utilized for prediction, prognosis, and therapeutic treatment. This paper aims to investigate the predictive power of Ras homolog family member B (RhoB) protein in rectal cancer. Methods: This study introduces the integration of pretrained convolutional neural networks and support vector machines (SVMs) for classifying biopsy samples of immunohistochemical expression of protein RhoB in rectal-cancer patients to validate its biologic measure in biopsy. Features of the immunohistochemical expression images were extracted by the pretrained networks and used for binary classification by the SVMs into two groups of less and more than 5-year survival rates. Results: The fusion of neural search architecture network (NASNet)-Large for deep-layer feature extraction and classifier using SVMs provided the best average classification performance with a total accuracy = 85%, prediction of survival rate of more than 5 years = 90%, and prediction of survival rate of less than 5 years = 75%. Conclusions: The finding obtained from the use of AI reported in this study suggest that RhoB expression on rectal-cancer biopsy can be potentially used as a biomarker for predicting survival outcomes in rectal-cancer patients, which can be informative for clinical decision making if the patient would be recommended for preoperative therapy.

Background: Over a decade, tissues dissected adjacent to primary tumors have been considered “normal” or healthy samples (NATs). However, NATs have recently been discovered to be distinct from both tumorous and normal tissues. The ability to predict the survival rate of cancer patients using NATs can open a new door to selecting optimal treatments for cancer and discovering biomarkers. Methods: This paper introduces an artificial intelligence (AI) approach that uses NATs for predicting the 5-year survival of pre-operative radiotherapy patients with rectal cancer. The new approach combines pre-trained deep learning, nonlinear dynamics, and long short-term memory to classify immunohistochemical images of RhoB protein expression on NATs. Results: Ten-fold cross-validation results show 88% accuracy of prediction obtained from the new approach, which is also higher than those provided from baseline methods. Conclusion: Preliminary results not only add objective evidence to recent findings of NATs’ molecular characteristics using state-of-the-art AI methods, but also contribute to the discovery of RhoB expression on NATs in rectal-cancer patients. Clinical impact: The ability to predict the survival rate of cancer patients is extremely important for clinical decision-making. The proposed AI tool is promising for assisting oncologists in their treatments of rectal cancer patients.

Abstract Background The association between body composition and survival in rectal cancer patients is still unclear. Therefore, we aimed to evaluate the impact of computed tomography (CT)-measured body composition on survival in rectal cancer patients, stratifying our analyses by sex, tumour location, tumour stage and radiotherapy. Methods This retrospective cohort study included 173 patients with rectal adenocarcinoma. CT colonography scans at the time of diagnosis were used to assess the skeletal muscle index (SMI) and the visceral adipose tissue area (VAT). The patients were divided into a low or high SMI group and a low or high VAT group according to previously defined cutoff values. Endpoints included cancer-specific survival (CSS) and overall survival (OS). Results In all patients, low SMI was associated with worse CSS (HR, 2.63; 95% CI, 1.35–5.12; P = 0.004) and OS (HR, 3.57; 95% CI, 2.01–6.34; P < 0.001) compared to high SMI. The differences remained significant after adjusting for potential confounders (CSS: adjusted HR, 2.28; 95% CI, 1.13–4.58; P = 0.021; OS: adjusted HR, 3.17; 95% CI, 1.73–5.82; P < 0.001). Low SMI was still related to a poor prognosis after stratifying by sex, tumour location, stage and radiotherapy (P < 0.05). High VAT was associated with better CSS (HR, 0.31; 95% CI, 0.11–0.84; P = 0.022) and OS (HR, 0.40; 95% CI, 0.17–0.97; P = 0.044) compared to low VAT among men with rectal cancer ≤ 10 cm from the anal verge. High VAT was associated with worse CSS (HR, 4.15; 95% CI, 1.10–15.66; P = 0.036) in women with rectal cancer ≤ 10 cm from the anal verge. Conclusions Low SMI was associated with worse survival. High VAT predicted better survival in men but worse survival in women. The results suggest that CT-measured body composition is a useful tool for evaluating the prognosis of rectal cancer patients and demonstrate the need to include the sex and the tumour location in the analyses.

Due to the heterogeneity of colon cancer, surgery, chemotherapy, and radiation are ineffective in all cases. The genomic profile and biomarkers associated with the process are considered in personalized medicine, along with the patient's personal history. It is based on the response of the targeted therapies to specific genetic variations. The patient's genetic transcriptomic and epigenetic features are evaluated, and the best therapeutic approach and diagnostic testing are identified through personalized medicine. This review aims to summarize all the necessary, updated information on colon cancer related to personalized medicine. Personalized medicine is gaining prominence as generalized treatments are finding it challenging to contain colon cancer cases which currently rank fourth among global cancer incidence while being the fifth largest in total death cases worldwide. In personalized therapy, patients are grouped into specific categories, and the best therapeutic approach is chosen based on evaluating their molecular features. Various personalized strategies are currently being explored in the treatment of colon cancer involving immunotherapy, phytochemicals, and other biomarker-specific targeted therapies. However, significant challenges must be overcome to integrate personalized medicine into healthcare systems completely. We look at the various signaling pathways and genetic and epigenetic alterations associated with colon cancer to understand and identify biomarkers useful in targeted therapy. The current personalized therapies available in colon cancer treatment and the strategies being explored to improve the existing methods are discussed. This review highlights the advantages and limitations of personalized medicine in colon cancer therapy. The current scenario of personalized medicine in developed countries and the challenges faced in middle- and low-income countries are also summarized. Finally, we discuss the future perspectives of personalized medicine in colon cancer and how it could be integrated into the healthcare systems.

Introduction: Accumulating evidence has implicated a pivotal role for FOXO3, FOXM1 and SIRT6 in cancer progression. The majority of researches focused on the functions of these proteins in drug resistance, but their relationships with radiotherapy (RT) response remain unclear. In this study, we examined protein expression of FOXO3, FOXM1 and SIRT6 and their clinical significance in a Swedish rectal cancer trial of preoperative RT. Methods: Expression of FOXO3, FOXM1 and SIRT6 protein was examined by immunohistochemistry in patient samples. Genetic analysis of FOXO3, FOXM1 and SIRT6 were performed by cBioportal and MEXPRESS database. Gene-gene network analysis was conducted using GeneMANIA. Functional enrichment analysis was performed based on LinkedOmics and Metascape online software. Results: FOXO3 and FOXM1were mainly expressed in the cytoplasm in both normal and tumour tissues, and SIRT6 in both the cytoplasm and nucleus in normal and tumour tissues. FOXO3 and FOXM1 expression increased from normal mucosa to primary cancer (P 0.05). Genetic analysis indicated that DNA methylation status contributed to FOXO3 overexpression. Functional enrichment analysis demonstrated that FOXO3 was closely related to metabolism-related signalling pathway which in turn associated with cancer radioresistance. Moreover, there were strong gene–gene interactions between FOXO3 and metabolism-related signalling. Conclusions: Our findings suggest that FOXO3 may be a prognostic factor in rectal cancer patients with RT.

To ascertain the possibility of cultivating maize using biological nitrogen fixation (BNF) by leguminous green manure crops in maize/leguminous green manure intercropping systems, BNF and nitrogen (N) transfer were studied in Xining and Wuwei, two typical northwestern Chinese cities. The experimental treatments included monocultured maize, monocultured green manures (hairy vetch and common vetch), and their intercropping systems. The proportions of N derived from the atmosphere (%Ndfa) in intercropping systems were not significantly different from that in monocultured green manure systems at either experimental site, except for that in hairy vetch (HV) in Xining. The amount of N derived from the atmosphere (Ndfa) of common vetch (CV) significantly decreased from 1.16 and 1.10 g/pot in monoculture to 0.77 and 0.55 g/pot when intercropped with maize, in Xining and Wuwei, respectively, and the Ndfa of HV when intercropped significantly decreased from 1.02 to 0.48 g/pot in Xining. In the intercropping systems in Xining and Wuwei, the amounts of N transferred (Ntransfer) from CV to maize were 21.54 and 26.81 mg/pot, accounting for 32.9 and 5.9% respectively of the N accumulation in maize, and the values of Ntransfer from HV to maize were 39.61 and 46.22 mg/pot, accounting for 37.0 and 23.3%, respectively, of the N accumulation in maize. Path analysis showed that soil nutrient and green manure biomass were mainly related to Ndfa, and that δ15N had a primary relationship with Ntransfer. We found that 5.9–37.0% of N accumulation in maize was transferred from green manures, and that the N transfer ability to maize of HV was higher than that of CV. In conclusion, intercropping with leguminous green manures provided a feasible way for maize to effectively utilize biologically fixed N.

IntroductionThe value of adjuvant chemotherapy for rectal cancer patients is debated and varies in different subgroups. One such subgroup is mucinous adenocarcinoma (MAC), which is more treatment resistant compared to non-mucinous adenocarcinoma (NMAC). To date, mucinous histology is not taken into account when deciding on adjuvant treatment strategy. This is the first study to exclusively include patients with rectal cancer, then separate MAC and NMAC and compare the survival in patients that had or did not have adjuvant chemotherapy.Material and methodsThe study included retrospective register data from 365 Swedish patients with stage II-IV rectal adenocarcinoma, 56 patients with MAC and 309 patients with NMAC. All patients were considered curative, had surgery with total mesorectal excision in 2004-2013, and were followed up until death or 2021.ResultsPatients with MAC that had adjuvant chemotherapy had better overall survival (OS, HR 0.42; CI 95%: 0.19-0.93; p = 0.032) and a trend towards better cancer-specific survival (CSS, HR 0.41 CI 95%: 0.17-1.03; p = 0.057) compared to patients without chemotherapy (HR 0.42; CI 95%: 0.19-0.93; p = 0.032). The difference in OS was still significant even after adjusting for sex, age, stage, differentiation, neoadjuvant chemotherapy and preoperative radiotherapy (HR 0.40; CI 95%: 0.17-0.92; p = 0.031). There was no such difference in the NMAC patients except in the stage-by-stage subgroup analyses where patients in stage IV had better survival after adjuvant chemotherapy.ConclusionsThere may be a difference in treatment response to adjuvant chemotherapy between MAC and NMAC patients. Patients with MAC could possibly benefit from adjuvant chemotherapy in stages II-IV. Further studies are however needed to confirm these results.

AIM:To evaluate the effect of Yangxue Runmu formula combined with sodium hyaluronate on dry eye after cataract surgery by ocular surface analyzer.METHODS: Totally 80 patients with dry eye after cataract surgery in our hospital from June 2019 to December 2020 were selected and divided into control group and observation group by random number table method, 40 cases in each group. The control group was treated with sodium hyaluronate eye drops, and the observation group was treated with Yangxue Runmu formula combined with sodium hyaluronate eye drops. The index levels of ocular surface analyzer and fluorescein staining(FL)score were compared between the two groups.RESULTS: After treatment, the wet length of tear film, first non-invasive tear break-up time(NIBUTf), average non-invasive tear break-up time(NIBUTav)and tear meniscus height(LTMH)in the two groups were markedly higher than those before treatment(all P

Statins are an essential medication class in the treatment of lipid diseases because they inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. They reduce cholesterol levels and reduce the risk of cardiovascular disease in both primary and secondary prevention. In addition to their powerful pharmacologic suppression of cholesterol production, statins appear to have pleitropic effects in a wide variety of other diseases by modulating signaling pathways. In recent years, statins have seen a large increase in interest due to their putative anticancer effects. Statins appear to cause upregulation or inhibition in key pathways involved in cancer such as inhibition of proliferation, angiogenesis, and metastasis as well as reducing cancer stemness. Further, statins have been found to induce oxidative stress, cell cycle arrest, autophagy, and apoptosis of cancer cells. Interestingly, clinical studies have shown that statin use is associated with a decreased risk of cancer formation, lower cancer grade at diagnosis, reduction in the risk of local reoccurrence, and increasing survival in patients. Therefore, our objective in the present review is to summarize the findings of the publications on the underlying mechanisms of statins’ anticancer effects and their clinical implications.

Abstract Purpose To develop new and effective biomarkers for the diagnosis of colorectal cancer (CRC). Experimental design The serum expression of ITGB4 (49 CRC and 367 HC) was detected by enzyme‐linked immunosorbent assay (ELISA), and its diagnostic value was analyzed using the receiver operating characteristic (ROC) curve. The sensitivity and specificity of ITGB4 in CRC diagnosis were calculated through statistical analysis. The optimal clinical cutoff value was calculated using the Youden index, and diagnostic efficacy was analyzed in a larger serum sample (98 CRC and 1631 non‐CRC). The expression of ITGB4 was measured by CyTOF (cell experimental technology) at the single‐cell level, and characteristics were analyzed using viSNE and SPADE TREE. Results Serum ITGB4 and CEA levels were significantly higher in CRC patients than in HC and non‐CRC patients. The use of serum ITGB4 levels for the diagnosis of CRC has a high sensitivity (79%) but not high specificity when the clinical cutoff value was 0.70 ng/mL. However, the optimal cutoff value was 1.6 ng/mL with 86.2% specificity and 52.0% sensitivity, and the diagnostic efficacy was greatly improved with high specificity (82.0%) and sensitivity (71.4%) when combined with CEA. ITGB4 expression characteristics were measured and related to the expression of EpCAM, Ck8/18, and perforin at the single‐cell level. Single‐cell analysis showed that cell clusters with low expression of CK8/18 and ITGB4 were more sensitive to 5FU and radiotherapy (RT). Conclusions ITGB4 is an effective diagnostic serum biomarker and a potential therapeutic target for CRC.

We recently reported that activation of Trop-2 through its cleavage at R87-T88 by ADAM10 underlies Trop-2–driven progression of colon cancer. However, the mechanism of action and pathological impact of Trop-2 in metastatic diffusion remain unexplored. Through searches for molecular determinants of cancer metastasis, we identified TROP2 as unique in its up-regulation across independent colon cancer metastasis models. Overexpression of wild-type Trop-2 in KM12SM human colon cancer cells increased liver metastasis rates in vivo in immunosuppressed mice. Metastatic growth was further enhanced by a tail-less, activated ΔcytoTrop-2 mutant, indicating the Trop-2 tail as a pivotal inhibitory signaling element. In primary tumors and metastases, transcriptome analysis showed no down-regulation of CDH1 by transcription factors for epithelial-to-mesenchymal transition, thus suggesting that the pro-metastatic activity of Trop-2 is through alternative mechanisms. Trop-2 can tightly interact with ADAM10. Here, Trop-2 bound E-cadherin and stimulated ADAM10-mediated proteolytic cleavage of E-cadherin intracellular domain. This induced detachment of E-cadherin from β-actin, and loss of cell-cell adhesion, acquisition of invasive capability, and membrane-driven activation of β-catenin signaling, which were further enhanced by the ΔcytoTrop-2 mutant. This Trop-2/E-cadherin/β-catenin program led to anti-apoptotic signaling, increased cell migration, and enhanced cancer-cell survival. In patients with colon cancer, activation of this Trop-2–centered program led to significantly reduced relapse-free and overall survival, indicating a major impact on progression to metastatic disease. Recently, the anti-Trop-2 mAb Sacituzumab govitecan-hziy was shown to be active against metastatic breast cancer. Our findings define the key relevance of Trop-2 as a target in metastatic colon cancer.

BackgroundPrevious studies suggested that unhealthy sleep patterns were closely associated with gastrointestinal diseases, but the impact of unhealthy sleep duration on chronic constipation has not been well studied until now. In this study, we aim to explore the association between sleep duration and constipation among males and females.MethodsWe utilized the US National Health and Nutrition Examination Surveys data from 2005 to 2010, and adults (≥20 years old) who completed the sleep and bowel health questionnaires were enrolled in this observational study. Sleep duration was categorized into four groups: very short sleep (

Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.

BackgroundPrevious studies supported that dietary factor was associated with constipation, but the relationship between dietary energy intake and constipation has not been well-studied. Therefore, we aimed to evaluate the prevalence and correlation between energy intake and constipation among men and women.MethodsThese observational analyses included 12,587 adults (≥20 years) from the 2005–2010 cycles of the National Health and Nutrition Examination Surveys (NHANES). Constipation was defined as Bristol Stool Scale Type 1 (separate hard lumps, like nuts) or Type 2 (sausage-like but lumpy). Total energy intake was obtained from the two 24-h dietary recalls and averaged. We used the logistic regression model in Generalized Linear Model (GLM) function, controlling demographic, lifestyle, and dietary factors, to estimate the association between energy intake and constipation among men and women.ResultsThe overall weighted incidence of constipation in this research was 7.4%, the incidence in women and men was 10.4 and 4.3%, respectively. After multivariable adjustment, middle energy consumption correlated with decreased risk of constipation in men (OR:0.5, 95% CI:0.29–0.84), and lower-middle energy intake increased the constipation risk in women (OR: 1.56, 95% CI: 1.15–2.13). High energy consumption was not associated with increased or decreased constipation risk.ConclusionsTo our knowledge, this is the first research to investigate the association between energy intake and constipation; the study demonstrates that appropriate energy consumption can help reduce the risk of constipation in men, and relatively low energy intake is associated with increased constipation risk in women.

Our previous study demonstrated that miR-124 was downregulated in colorectal cancer (CRC) compared with normal mucosa, and the downregulated expression of miR-124 was an independent prognostic factor in CRC patients. However, the function of miR-124 in CRC patients treated with chemotherapy is currently unclear. The aim of this study was to determine the miR-124 expression and its regulative role in oxaliplatin (L-OHP)-based chemotherapy of CRC patients. We observed that low miR-124 expression was correlated with worse overall survival (OS) in the 220 patients who received postoperative chemotherapy of 5-fluorouracil [5-FU]+leucovorin+L-OHP (FOLFOX) or capecitabine+L-OHP (XELOX). miR-124 overexpression promoted L-OHP-induced, but not 5-FU-induced, cytotoxicity and apoptosis in HT29 and SW480 cells. CAPN2 was a direct target of miR-124, and its protein expression was reduced by forced expression of miR-124. miR-124 inhibited tumorigenesis and promoted OS of mice bearing xenograft tumors, especially upon L-OHP treatment. miR-124 also promoted L-OHP-induced apoptosis and restrained CAPN2 protein expression in xenograft tumors. Our results suggest that miR-124 could be considered as both a predictor of L-OHP-based chemotherapy for personalized treatment and a therapeutic target for CRC.

(1) Background: CD163, a specific macrophage receptor, affects the progression of malignant tumors. Unfortunately, the regulation and expression of CD163 are poorly understood. In this study, we determined the expressions of CD163 in TMA samples from CRC patients and combined them with patient data from several Swedish hospitals. (2) Methods: The expressions of CD163 in tissue samples from CRC patients were examined. After combining 472 CRC patients’ gene expression and 438 CRC patients’ clinical data with the TCGA database, 964 cases from the GEO database, and experimental expression data from 1247 Swedish CRC patients, we selected four genes (PCNA, LOX, BCL2, and CD163) and analyzed the tumor-infiltrating immune cells (TICs) and CRC prognosis. (3) Results: Based on histopathological TMA analysis, CD163 was strongly expressed in the stroma of both normal and cancer tissues, and the expressions in normal and cancer cells varied from negative to strong. The results from public databases show decreased expression of CD163 in cancer tissue compared to normal mucosa (|log FC| > 1 and FDR < 0.01), and it is a negative prognostic factor for CRC patients (p-value < 0.05). Through tumor microenvironment (TME) analysis, we found a potential influence of CD163 on immune cell infiltration. Furthermore, the enrichment analysis indicated the possible interaction with other proteins and biological pathways. (4) Conclusions: CD163 is expressed differently in CRC tissue and is a negative prognostic factor. Its expression is associated with the TME and tumor purity of CRC. Considering all results, CD163 has the potential to be a predictive biomarker in the investigation of CRC.

The role of microRNA 122 (miR-122) in colorectal cancer (CRC) has not been widely investigated. In the current study, we aimed to identify the prominent gene and protein interactors of miR122 in CRC. Based on their binding affinity, these targets were chosen as candidate genes for the creation of miR122–mRNA duplexes. Following this, we examined the miRNA-mediated silencing mechanism using the gene-silencing complex protein Argonaute (AGO). Public databases, STRING, and GeneMANIA were utilized to identify major proteins and genes interacting with miR-122. DAVID, PANTHER, UniProt, FunRich, miRwalk, and KEGG were used for functional annotation, pathway enrichment, binding affinity analysis, and expression of genes in different stages of cancer. Three-dimensional duplexes of hub genes and miR-122 were created using the RNA composer, followed by molecular interaction analysis using molecular docking with the AGO protein. We analyzed, classified, and scrutinized 93 miR-122 interactors using various bioinformatic approaches. A total of 14 hub genes were categorized as major interactors of miR-122. The study confirmed the role of various experimentally documented miR-122 interactors such as MTDH (Q86UE4), AKT1 (P31749), PTPN1 (P18031), MYC (P01106), GSK3B (P49841), RHOA (P61586), and PIK3CG (P48736) and put forth several novel interactors, with AKT3 (Q9Y243), NCOR2 (Q9Y618), PIK3R2 (O00459), SMAD4 (P61586), and TGFBR1 (P36897). Double-stranded RNA duplexes of the strongest interactors were found to exhibit higher binding affinity with AGO. In conclusions, the study has explored the role of miR-122 in CRC and has identified a closely related group of genes influencing the prognosis of CRC in multiple ways. Further, these genes prove to be targets of gene silencing through RNA interference and might serve as effective therapeutic targets in understanding and treating CRC.

Purpose: Adenomyosis is a relatively common disease among women of childbearing age. A minimally invasive alternative technique with low risks, faster recovery and decreased side effects is desired. We hypothesized that percutaneous microwave ablation (PMWA) under laparoscopic guidance would substantially reduce the risk of collateral thermal damage to the intestinal tract and relieve the pelvic adhesions. This study aimed to evaluate the feasibility, safety and efficacy of transvaginal ultrasound- and laparoscopy-guided PMWA for the treatment of adenomyosis. Materials and methods: From May 2015 to October 2017, a total of 70 patients with symptomatic adenomyosis who underwent transvaginal ultrasound- and laparoscopy-guided PMWA were included in this study. The technical efficacy and complications of PMWA were assessed. Meanwhile, the uterine volume, lesion volume, symptom severity score (SSS) and visual analog scale (VAS) score before PMWA and at 1, 6 and 12 months after PMWA were recorded. Results: PMWA was successfully performed with transvaginal ultrasound guidance and laparoscope assistance in all patients. No major complication was found after PMWA in any patients. The uterine volume, lesion volume, SSS and VAS were all decreased significantly at follow-up (p

Herein, xylan-g-PMMA was synthesized by grafting poly(methyl methacrylate) (PMMA) onto xylan and characterized by FT-IR and HSQC NMR spectroscopies, and the xylan-g-PMMA/TiO2 solution was used to electrospun nanofibers at the voltage of 15 Kv, which was the first time employing xylan to electrospun nanofibers. Moreover, the electrospinning operating parameters were optimized by assessing the electrospinning process and the morphology of electrospun fibers, as follows: the mixed solvent of DMF and chloroform in a volume ratio of 5:1, an anhydroxylose unit (AXU)/MMA molar ratio lower than 1:2, the flow speed of 0.00565–0.02260 mL/min, and a receiving distance of 10–15 cm. Diameters of the electrospun fibers increased with increasing DMF content in the used solvent mixture, MMA dosage, and receiving distance. TiO2 nanoparticles were successfully dispersed in electrospun xylan-g-PMMA nanofibers and characterized by scanning electron microscopy, energy dispersive X-ray diffraction spectrum, and X-ray photoelectron spectroscopy, and their application for methylene blue (MB) degradation presented above 80% photocatalytic efficiency, showing the good potential in water treatment.

Background. The incidence of colorectal cancers has been constantly increasing. Although the mortality has slightly decreased, it is far from satisfaction. Precise early diagnosis for colorectal cancer has been a great challenge in order to improve patient survival. Patients and Methods. We started with searching for protein biomarkers based on our colorectal cancer biomarker database (CBD), finding differential expressed genes (GEGs) and non-DEGs from RNA sequencing (RNA-seq) data, and further predicted new biomarkers of protein–protein interaction (PPI) networks by machine learning (ML) methods. The best-selected biomarker was further verified by a receiver operating characteristic (ROC) test from microarray and RNA-seq data, biological network, and functional analysis, and immunohistochemistry in the tissue arrays from 198 specimens. Results. There were twelve proteins (MYO5A, CHGA, MAPK13, VDAC1, CCNA2, YWHAZ, CDK5, GNB3, CAMK2G, MAPK10, SDC2, and ADCY5) which were predicted by ML as colon cancer candidate diagnosis biomarkers. These predicted biomarkers showed close relationships with reported biomarkers of the PPI network and shared some pathways. An ROC test showed the CHGA protein with the best diagnostic accuracy (AUC = 0.9 in microarray data and 0.995 in RNA-seq data) among these candidate protein biomarkers. Furthermore, immunohistochemistry examination on our colon cancer tissue microarray samples further confirmed our bioinformatical prediction, indicating that CHGA may be used as a potential biomarker for early diagnosis of colon cancer patients. Conclusions. CHGA could be a potential candidate biomarker for diagnosing earlier colon cancer in the patients.

Objective To investigate the mechanism by which curcumin prevents lung injury in a rat model of limb ischaemia-reperfusion injury. Methods Rats were randomized into four groups ( n = 20): control group (sham group); ischaemia-reperfusion group (I/R group); curcumin group (I/R+Cur group); and inhibitor of agomir-21 group (I/R+Cur+antagomir-21 group). At 3 h after reperfusion, lung tissues were collected for histopathology and immunohistochemistry to determine the apoptosis index (AI). Lung injury score (LIS) and lung wet/dry (W/D) ratio were determined. Lung microRNA-21 (miR-21) mRNA levels were measured using reverse transcription–polymerase chain reaction. Toll-like receptor 4 (TLR4) and nuclear factor kappa-B p65 (NF-κB p65) protein levels were measured by Western blot analysis. Tumour necrosis factor (TNF)-α and interleukin (IL)-1β levels were determined by enzyme-linked immunosorbent assays. Results In the I/R group, the W/D, LIS, AI, miR-21 mRNA, TLR4, NF-κB p65, TNF-α and IL-1β were significantly increased and the PaO 2 was decreased compared with the sham group. Evidence of lung injury was observed in the I/R group and this was alleviated in the I/R+Cur group. An inhibitor of miR-21 (antagomir-21) reversed the protective effects of curcumin. Conclusion Curcumin post-treatment can alleviate the lung injuries induced by limb ischaemia-reperfusion via downregulating the levels of miR-21 mRNA.

Differential expressions and functions of various micoRNAs (miRNAs) have been intensively studied in both colon and rectal cancers. However, the importance of miRNAs on radiotherapy (RT) response and clinical outcome in rectal cancer patients remains unclear. In this study, we used real-time polymerase chain reaction to examine the expressions of miR-302a, miR-105, and miR-888 in normal mucosa and cancer tissue from rectal cancer patients with and without preoperative RT. The biological function of miR-302a, miR-105, and miR-888 expression was further analyzed and identified through the public databases: TCGA (The Cancer Genome Atlas) and GEPIA (Gene Expression Profiling Interactive Analysis). The results showed that the expression of miR-105 in rectal cancer was higher than that in normal mucosa in RT (P = 0.042) and non-RT patients (P = 0.003) and was associated with mucinous histological type (P = 0.004), COX-2 (P = 0.042), and p73 expression (P = 0.030). The expression of miR-302a was shown more frequently in cancers with necrosis (P = 0.033) and with WRAP53 expression (P = 0.015), whereas miR-888 expression occurred more frequently in tumors with protein the expression of survivin (P = 0.015), AEG-1 (astrocyte elevated gene-1) (P = 0.003), and SATB1 (special AT-rich sequence binding protein 1) (P = 0.036). Moreover, TargetScan also predicted AEG-1 and SATB1 as putative targets for miR-888. The miRNA–gene network analysis showed that ABI2 was associated with all the three miRNAs, with lower expression and good diagnostic value in rectal cancers. The TCGA database demonstrated the association of miR-105 expression with high carcinoembryonic antigen level (P = 0.048). RT reduced the expressions of miR-302a, miR-105, and miR-888. Prognostic analysis showed that miR-888 expression was independently associated with worse survival of patients without RT [overall survival, P = 0.001; disease-free survival, P = 0.009]. Analysis of biological function revealed that the protein serine/threonine kinase activity and PI3K-AKT signaling pathway were the most significantly enriched functions and pathways, respectively. Our findings suggest that miR-105 is involved in rectal cancer pathogenesis and miR-888 is associated with prognosis. MiR-302a, miR-105, and miR-888 have potential influence on the pathogenesis, RT, and prognosis of rectal cancer.

Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear.Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO.Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC.Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.

Background: Rectal cancer is a disease characterized with tumor heterogeneity. The combination of surgery, radiotherapy, and chemotherapy can reduce the risk of local recurrence. However, there is a significant difference in the response to radiotherapy among rectal cancer patients even they have the same tumor stage. Despite rapid advances in knowledge of cellular functions affecting radiosensitivity, there is still a lack of predictive factors for local recurrence and normal tissue damage. The tumor protein DNp73 is thought as a biomarker in colorectal cancer, but its clinical significance is still not sufficiently investigated, mainly due to the limitation of human-based pathology analysis. In this study, we investigated the predictive value of DNp73 in patients with rectal adenocarcinoma using image-based network analysis.Methods: The fuzzy weighted recurrence network of time series was extended to handle multi-channel image data, and applied to the analysis of immunohistochemistry images of DNp73 expression obtained from a cohort of 25 rectal cancer patients who underwent radiotherapy before surgery. Two mathematical weighted network properties, which are the clustering coefficient and characteristic path length, were computed for the image-based networks of the primary tumor (obtained after operation) and biopsy (obtained before operation) of each cancer patient.Results: The ratios of two weighted recurrence network properties of the primary tumors to biopsies reveal the correlation of DNp73 expression and long survival time, and discover the non-effective radiotherapy to a cohort of rectal cancer patients who had short survival time.Conclusion: Our work contributes to the elucidation of the predictive value of DNp73 expression in rectal cancer patients who were given preoperative radiotherapy. Mathematical properties of fuzzy weighted recurrence networks of immunohistochemistry images are not only able to show the predictive factor of DNp73 expression in the patients, but also reveal the identification of non-effective application of radiotherapy to those who had poor overall survival outcome.

This research was performed to estimate the potential effects of Di (2-ethylhexyl) phthalate (DEHP) on changes of ovarian miRNA expression profile during mouse primordial follicle assembly using miRNAs-seq analysis. The ovaries of newborn mice were collected and in vitro cultured with different concentration of DEHP for 72 h. Then they were prepared for miRNAs-seq analysis. The results indicated that DEHP exposure altered ovarian miRNA expression profile of newborn mice. Eighteen differentially expressed miRNAs were screened after 100 μM DEHP exposure. The target mRNAs of differentially expressed miRNAs were predicted and further analyzed through gene ontology (GO) enrichment analysis and pathway enrichment analysis. Our results showed that the differentially expressed miRNAs from DEHP exposure can regulate ovarian development by targeting mRNAs involved in MAPK, mTOR, FoxO signaling pathways. Three miRNAs of miR-32-5p, miR-19a-3p, and miR-141-3p were randomly selected from the differentially expressed miRNAs to quantify their expression level by miRNA qRT-PCR. The results of qRT-PCR and miRNA-seq were consistent. Considering one of its target gene PTEN of miR-19a-3p and the decreased level of pAKT and increased Bax/Bcl-2 under DEHP exposure, we speculated that the altered expression of miR-19a-3p by DEHP exposure affected mouse primordial follicle assembly via PI3K/AKT1/mTOR signaling pathway. Epigenetic changes are one of the most important targets of toxicant exposure. The effects of DEHP exposure on microRNA (one of the epigenetic regulators) expression profile were uncovered to enrich the research on relationship of epigenetics and toxicant exposure.

The present study was carried out to find the best treatments for enhancing the ration of insertion of a desired gene construct (pEGFP-N1) onto the sperm of buffalo as the first step for the production of transgenic buffalo using sperm mediated gene transfer (SMGT). The tested conditions were plasmid DNA concentration, sperm concentration, transfecting agent concentration: Dimethyle sulphoxide (DMSO) and time of transfection. The study proved that the best conditions for producing transgenic embryos were incubation sperm solution its concentration is 107/ml sperm with 3% DMSO: with 20 µg/ml from the linarized DNA, for 15 min at 4 °C are the best conditions to produce transgenic buffalo embryo using sperm mediated gene transfer.

Cellulose, hemicellulose, and lignin are three kinds of biopolymer in lignocellulosic biomass, and the utilization of the three biopolymers to synthesize hydrogel adsorbent could protect the environment and enhance the economic value of the biomass. A novel hydrogel adsorbent was prepared using cellulose, lignin, and hemicellulose of wheat straw by a one-pot method, and the adsorbent showed excellent adsorption performance for copper(II) ions. Scanning electron microscopy and Fourier transform infrared spectroscopy analysis showed that the prepared straw-biopolymer-based hydrogel had porous structure, and cellulose fibrils had crosslinked with lignin and hemicellulose by poly(acrylic acid) chains. The effects of contact time, initial concentration, and temperature on the copper(II) ion removal using the prepared hydrogels were investigated, and the obtained results indicated that the adsorption kinetics conformed to the pseudo-second-order and Elovich equation models and the adsorption isotherm was in accord with the Freundlich model. The adsorption thermodynamics study indicated that the adsorption process was spontaneous and accompanied by heat. X-ray photoelectron spectroscopy analysis revealed that the adsorption behavior resulted from ion exchange. The prepared hydrogel based on cellulose, hemicellulose, and lignin could be used for water treatment and soil remediation because of its high performances of excellent heavy metal ion removal and water retention.

Tumor breakthrough is driven by genetic or epigenetic variations which assist in initiation, migration, invasion and metastasis of tumors. Astrocyte elevated gene-1 (AEG-1) protein has risen recently as the crucial factor in malignancies and plays a potential role in diverse complex oncogenic signaling cascades. AEG-1 has multiple roles in tumor growth and development and is found to be involved in various signaling pathways of: (i) Ha-ras and PI3K/AKT; (ii) the NF-κB; (iii) the ERK or mitogen-activated protein kinase and Wnt or β-catenin and (iv) the Aurora-A kinase. Recent studies have confirmed that in all the hallmarks of cancers, AEG-1 plays a key functionality including progression, transformation, sustained angiogenesis, evading apoptosis, and invasion and metastasis. Clinical studies have supported that AEG-1 is actively intricated in tumor growth and progression which includes esophageal squamous cell, gastric, colorectal, hepatocellular, gallbladder, breast, prostate and non-small cell lung cancers, as well as renal cell carcinomas, melanoma, glioma, neuroblastoma and osteosarcoma. Existing studies have reported that AEG-1 expression has been induced by Ha-ras through intrication of PI3K/AKT signaling. Conversely, AEG-1 also activates PI3K/AKT pathway and modulates the defined subset of downstream target proteins via crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling cascade which further plays a crucial role in metastasis. Thus, AEG-1 may be employed as a biomarker to discern the patients of those who are likely to get aid from AEG-1-targeted medication. AEG-1 may play as an effective target to repress tumor development, occlude metastasis, and magnify the effectiveness of treatments. In this review, we focus on the molecular mechanism of AEG-1 in the process of carcinogenesis and its involvement in regulation of crosstalk between the PI3K/AKT/mTOR and Hedgehog signaling. We also highlight the multifaceted functions, expression, clinicopathological significance and molecular inhibitors of AEG-1 in various cancer types.

There is a need to personalize the treatment for rectal cancer patients. The aim of this study was to analyze therapy response and prognosis after preoperative radiotherapy in rectal cancer patients with mucinous adenocarcinoma compared to those with non-mucinous adenocarcinoma. The study included retrospectively collected data from 433 patients, diagnosed with rectal cancer in the South East health care region in Sweden between 2004 and 2012. Patients with non-mucinous adenocarcinoma that received short-course radiotherapy before surgery had better overall survival, cancer specific survival, and disease-free survival, as well as distant- and local-recurrence-free survival (p = 0.003, p = 0.001, p = 0.002, p = 0.002, and p = 0.033, respectively) compared to the patients that received long-course radiotherapy with concomitant capecitabine. The results were still significant after adjusting for sex, age, stage, differentiation, and chemotherapy in the neoadjuvant and/or adjuvant setting, except for local-recurrence-free survival that was trending towards significance (p = 0.070). In patients with mucinous adenocarcinoma, no difference in survival was seen when comparing patients that had short-course radiotherapy and patients that had long-course radiotherapy. However, none of 18 patients with mucinous adenocarcinoma treated with long-course radiotherapy had local tumor progression, compared to 7% of 67 patients with non-mucinous adenocarcinoma. The results indicate that mucinous adenocarcinoma and non-mucinous adenocarcinoma may respond differently to radiotherapy.

Background and Purpose: Radiation therapy has long been contemplated as an important mode in the treatment of rectal cancer. However, there are few ideal tools available for clinicians to make a radiotherapy decision at the time of diagnosis for rectal cancer. The purpose of this study was to assess whether biomarkers expressed in the biopsy could help to choose the suitable therapy and provide predictive and/or prognostic information. Experimental Design: In total, 30 biomarkers were analyzed in 219 biopsy samples before treatment to discover the possibility of using them as an indicator for radiotherapy selection, diagnosis, survival and recurrence. Results: Twenty-two biomarkers (COX2-RT, COX2-NonRT, etc.; 36.67%) had diagnostic value. For survival, four biomarkers (NFKBP65, p130, PINCH and PPAR) were significant in regulating gene promoter activity and overall survival, while four had a trend (AEG1, LOX, SATB1 and SIRT6). Three biomarkers (COX2, PINCH and WRAP53) correlated with disease-free survival, while eight had a trend (AEG1, COX2, Ki67, LOX, NFKBP65, PPAR and SATB1). Four biomarkers (COX2-RT, NFKBP65cyto-RT, P130cyto-NonRT and PPARcyto-RT) were independent prognostic factors for recurrence. NFKBP65 and SIRT6 were significantly correlated with lymph node metastasis regardless of radiation. Patients with high AEG1, LOX, NFKBP65, PPAR and SATB1 had or showed a positive trend for better survival after radiotherapy, while those with positive PINCH and WRAP53 expression would not benefit from radiotherapy. Conclusions: AEG1, LOX, NFKBP65cyto, PPAR and SATB1 could be used as indicators for choosing radiotherapy. COX2-RT, COX2-NonRT and some other biomarkers may provide additional help for diagnosis.

AIM: To investigate the angiogenesis effect and protective mechanism of cordycepin on rhesus macaque choroid-retinal endothelial(RF/6A)cell line cultured in high glucose condition. METHODS: Cultured RF/6A cells were divided into normal control group, high glucose group and high glucose(HG)+ different concentration cordycepin groups(HG+10μg/mL group, HG+50μg/mL group, HG+100μg/mL group). The cell proliferation was assessed using cholecystokinin octapeptide dye after treated for 48h. The cell migration was investigated by a Transwell assay. The tube formation was measured on Matrigel. Furthermore, the impact of cordycepin on high glucose-induced activation of VEGF and VEGF receptor 2(VEGFR-2)was tested by Western blot analysis. RESULTS: Compared with normal control group, cell viability markedly increased in high glucose group(PPPPPPvs normal control group, oppositely gradually decreased with the increase of cordycepin concentrations, and had a statistically significant difference vs high glucose group(PCONCLUSION: Cordycepin can suppress the proliferation, migration and tubu formation of RF/6A in high glucose condition, might via inhibiting expression of VEGF and VEGFR-2.

Refractory Glaucoma is a kind of intractable eye disease with strong destruction and high blindness rate, the failure rate of which is very high.The mainly reason is fibroblasts hyperplasia and scarring on filtration mouth that hindered the drainage and diffusion of aqueous. Combined trabeculectomy, glaucoma drainage device implantation, and cyclophotocoagulation are the common surgical procedures for refractory glaucoma. So far, glaucoma drainage device implantation is regarded as the first-line choice. The authors focus on the clinical efficacy and prospect of the surgery way for refractory glaucoma.

Colorectal cancer (CRC) is one of the major causes of cancer death worldwide. In general, early diagnosis for CRC and individual therapy have led to better survival for the cancer patients. Accumulating studies concerning biomarkers have provided positive evidence to improve cancer early diagnosis and better therapy. It is, however, still necessary to further investigate the precise biomarkers for cancer early diagnosis and precision therapy and predicting prognosis. In this study, AI-assisted systems with bioinformatics algorithm integrated with microarray and RNA sequencing (RNA-seq) gene expression (GE) data has been approached to predict microRNA (miRNA) biomarkers for early diagnosis of CRC based on the miRNA-messenger RNA (mRNA) interaction network. The relationships between the predicted miRNA biomarkers and other biological components were further analyzed on biological networks. Bayesian meta-analysis of diagnostic test was utilized to verify the diagnostic value of the miRNA candidate biomarkers and the combined multiple biomarkers. Biological function analysis was performed to detect the relationship of candidate miRNA biomarkers and identified biomarkers in pathways. Text mining was used to analyze the relationships of predicted miRNAs and their target genes with 5-fluorouracil (5-FU). Survival analyses were conducted to evaluate the prognostic values of these miRNAs in CRC. According to the number of miRNAs single regulated mRNAs (NSR) and the number of their regulated transcription factor gene percentage (TFP) on the miRNA-mRNA network, there were 12 promising miRNA biomarkers were selected. There were five potential candidate miRNAs (miRNA-186-5p, miRNA-10b-5, miRNA-30e-5p, miRNA-21 and miRNA-30e) were confirmed as CRC diagnostic biomarkers, and two of them (miRNA-21 and miRNA-30e) were previously reported. Furthermore, the combinations of the five candidate miRNAs biomarkers showed better prediction accuracy for CRC early diagnosis than the single miRNA biomarkers. miRNA-10b-5p and miRNA-30e-5p were associated with the 5-FU therapy resistance by targeting the related genes. These miRNAs biomarkers were not statistically associated with CRC prognosis.

Tafazzin (TAZ) protein has been upregulated in various types of human cancers, although the basis for elevation is uncertain, it has been made definite that the effect of mutation in the hippo pathway, particularly when it is switched off, considerably activates tafazzin transcriptionally and thus this results in tissue or tumor overgrowth. Recent perceptions into the activity of tafazzin, have ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in neural stem cells. Being a downstream molecule in Hippo signalling, phosphorylation or dephosphorylation of tafazzin gene regulates its transcriptional activity and the stemness of mesenchymal stem cells. Commonly, extracellular matrix controls the stem cell fate commitment and perhaps tafazzin controls stemness through altering the extra cellular matrix. Extracellular matrix is generally made up of prime proteoglycans and the fate stabilization of the resulting lineages is surveilled by engineering these glycans. Tafazzin degradation and addition of proteoglycans affect physical attributes of the extracellular matrix that drives cell differentiation into various lineages. Thus, tafazzin along with major glycans present in the extracellular matrix is involved in imparting stemness. However, there are incoherent molecular events, wherein both tafazzin and the extracellular matrix components, together either activate or inhibit differentiation of stem cells. This review discusses about the role of tafazzin oncoprotein as a stemness factor.

Colon cancer is one of the major causes of cancer death worldwide. The five-year survival rate for the early-stage patients is more than 90%, and only around 10% for the later stages. Moreover, half of the colon cancer patients have been clinically diagnosed at the later stages. It is; therefore, of importance to enhance the ability for the early diagnosis of colon cancer. Taking advantages from our previous studies, there are several potential biomarkers which have been associated with the early diagnosis of the colon cancer. In order to investigate these early diagnostic biomarkers for colon cancer, human chromogranin-A (CHGA) was further analyzed among the most powerful diagnostic biomarkers. In this study, we used a logistic regression-based meta-analysis to clarify associations of CHGA expression with colon cancer diagnosis. Both healthy populations and the normal mucosa from the colon cancer patients were selected as the double normal controls. The results showed decreased expression of CHGA in the early stages of colon cancer as compared to the normal controls. The decline of CHGA expression in the early stages of colon cancer is probably a new diagnostic biomarker for colon cancer diagnosis with high predicting possibility and verification performance. We have also compared the diagnostic powers of CHGA expression with the typical oncogene KRAS, classic tumor suppressor TP53, and well-known cellular proliferation index MKI67, and the CHGA showed stronger ability to predict early diagnosis for colon cancer than these other cancer biomarkers. In the protein−protein interaction (PPI) network, CHGA was revealed to share some common pathways with KRAS and TP53. CHGA might be considered as a novel, promising, and powerful biomarker for early diagnosis of colon cancer.

In order to find out the most valuable biomarkers and pathways for diagnosis, therapy and prognosis in colorectal cancer (CRC) we have collected the published CRC biomarkers and established a CRC biomarker database (CBD: http://sysbio.suda.edu.cn/CBD/index.html). In this study, we analysed the single and multiple DNA, RNA and protein biomarkers as well as their positions in cancer related pathways and protein-protein interaction (PPI) networks to describe their potential applications in diagnosis, therapy and prognosis. CRC biomarkers were collected from the CBD. The RNA and protein biomarkers were matched to their corresponding DNAs by the miRDB database and the PubMed Gene database, respectively. The PPI networks were used to investigate the relationships between protein biomarkers and further detect the multiple biomarkers. The Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were used to analyse biological functions of the biomarkers. AI classification techniques were utilized to further verify the significances of the multiple biomarkers in diagnosis and prognosis for CRC. We showed that a large number of the DNA, RNA and protein biomarkers were associated with the diagnosis, therapy and prognosis in various degrees in the CRC biomarker networks. The CRC biomarkers were closely related to the CRC initiation and progression. Moreover, the biomarkers played critical roles in cellular proliferation, apoptosis and angiogenesis and they were involved in Ras, p53 and PI3K pathways. There were overlaps among the DNA, RNA and protein biomarkers. AI classification verifications showed that the combined multiple protein biomarkers played important roles to accurate early diagnosis and predict outcome for CRC. There were several single and multiple CRC protein biomarkers which were associated with diagnosis, therapy and prognosis in CRC. Further, AI-assisted analysis revealed that multiple biomarkers had potential applications for diagnosis and prognosis in CRC.

Xylan/poly(methacrylic acid) semi-interpenetrating network hydrogels were synthesized, and these hydrogels were fabricated using various ratios of xylan and methacrylic acid and cross-linked by N,N′-methylenebisacrylamide. The chemical structure and morphology of the prepared hydrogels were characterized by FT-IR spectroscopy and SEM analysis. The porous structure of the prepared hydrogels was found, and the interconnected porous channels increased when the content of xylan was increased in the hydrogels. The hydrogels presented excellent pH sensitivity and swelling reversibility. The dynamic swelling kinetics were also studied, and all obtained results indicated that the prepared xylan/poly(methacrylic acid) semi-IPN hydrogel could be used in biomedical fields, especially for drug release.

Acute appendicitis secondary to hernia incarceration presenting as scrotal swelling is exceptionally rare in neonates. We report a neonate who presented with tender swelling in the right scrotum. Ultrasonography detected features of a rare Amyand′s hernia. Surgical exploration and histopathological examination confirmed the diagnosis.

Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway, is upregulated in stroma associated with many common cancers. The finding suggested that PINCH may be involved in promoting tumor-stromal interactions that support tumor progression, and, if so, tumors with abundant PINCH stromal staining may have a worse prognosis. To test this hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa samples and 26 metastases in the lymph nodes were studied by immunohistochemistry, and 7 additional colon tumors were studied by Western blot analysis and immunofluorescence. The abundance of PINCH protein in stroma increased from normal mucosa to primary tumor to metastasis (P < .05), and was more intense at the invasive margin than it was in the intratumoral stroma. Strong stromal immunostaining for PINCH was shown to predict a worse outcome (rate ratio 2.1, 95% CI 1.16–3.37, P = .01), independent of Dukes stage, growth pattern, and tumor differentiation. PINCH was detected in fibroblasts, myofibroblasts, and a proportion of endothelial cells of the tumor vasculature, supporting the involvement of PINCH in promoting tumor-stromal interactions that support tumor progression. Interestingly, stromal staining for PINCH was an independent prognostic indicator in colorectal cancer.

BackgroundTafazzin (TAZ), a transmembrane protein contributes in mitochondrial structural and functional modifications through cardiolipin remodeling. TAZ mutations are associated with several diseases, but studies on the role of TAZ protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we investigated the TAZ expression in rectal cancer, and its correlation with RT, clinicopathological and biological variables in the patients participating in a clinical trial of preoperative RT.Methods140 rectal cancer patients were included in this study, of which 65 received RT before surgery and the rest underwent surgery alone. TAZ expression was determined by immunohistochemistry in primary cancer, distant, adjacent normal mucosa and lymph node metastasis. In-silico protein-protein interaction analysis was performed to study the predictive functional interaction of TAZ with other oncoproteins.ResultsTAZ showed stronger expression in primary cancer and lymph node metastasis compared to distant or adjacent normal mucosa in both non-RT and RT patients. Strong TAZ expression was significantly higher in stages I-III and non-mucinious cancer of non-RT patients. In RT patients, strong TAZ expression in biopsy was related to distant recurrence, independent of gender, age, stages and grade (p = 0.043, HR, 6.160, 95% CI, 1.063-35.704). In silico protein-protein interaction study demonstrated that TAZ was positively related to oncoproteins, Livin, MAC30 and FXYD-3.ConclusionsStrong expression of TAZ protein seems to be related to rectal cancer development and RT response, it can be a predictive biomarker of distant recurrence in patients with preoperative RT.

BackgroundPeroxisome proliferator-activated receptor delta (PPARD) is nuclear hormone receptor involved in colorectal cancer (CRC) differentiation and progression. The purpose of this study was to determine prevalence and spectrum of variants in the PPARD gene in CRC, and their contribution to clinicopathological endpoints.Methods and findingsDirect sequencing of the PPARD gene was performed in 303 primary tumors, in blood samples from 50 patients with ≥ 3 affected first-degree relatives, 50 patients with 2 affected first-degree relatives, 50 sporadic patients, 360 healthy controls, and in 6 colon cancer cell lines. Mutation analysis revealed 22 different transversions, 7 of them were novel. Three of all variants were somatic (c.548A>G, p.Y183C, c.425-9C>T, and c.628-16G>A). Two missense mutations (p.Y183C and p.R258Q) were pathogenic using in silico predictive program. Five recurrent variants were detected in/adjacent to the exons 4 (c.1-87T>C, c.1-67G>A, c.130+3G>A, and c.1-101-8C>T) and exon 7 (c.489T>C). Variant c.489C/C detected in tumors was correlated to worse differentiation (P = 0.0397).ConclusionsWe found 7 novel variants among 22 inherited or acquired PPARD variants. Somatic and/or missense variants detected in CRC patients are rare but indicate the clinical importance of the PPARD gene.

In the present study, we established an in vitro culture system suitable for generating fertilizable oocytes from premeiotic mouse female germ cells. These results were achieved after first establishing an in vitro culture system allowing immature oocytes from 12-14 day-old mice to reach meiotic maturation through culture onto preantral granulosa cell (PAGC) monolayers in the presence of Activin A (ActA). To generate mature oocytes from premeiotic germ cells, pieces of ovaries from 12.5 days post coitum (dpc) embryos were cultured in medium supplemented with ActA for 28 days and the oocytes formed within the explants were isolated and cocultured onto PAGC monolayers in the presence of ActA for 6-7 days. The oocytes were then subjected to a final meiotic maturation assay to evaluate their capability to undergo germinal vesicle break down (GVBD) and reach the metaphase II (MII) stage. We found that during the first 28 days of culture, a significant number of oocytes within the ovarian explants reached nearly full growth and formed preantral follicle-like structures with the surrounding somatic cells. GSH level and Cx37 expression in the oocytes within the explants were indicative of proper developmental conditions. Moreover, the imprinting of Igf2r and Peg3 genes in these oocytes was correctly established. Further culture onto PAGCs in the presence of ActA allowed about 16% of the oocytes to undergo GVBD, among which 17% reached the MII stage during the final 16-18 hr maturation culture. These MII oocytes showed normal spindle and chromosome assembly and a correct ERK1/2 activity. About 35% of the in vitro matured oocytes were fertilized and 53.44% of them were able to reach the 2-cell stage. Finally, around 7% of the 2-cell embryos developed to the morula/blastocyst stage.