Pan-cancer transcriptomic data of ABI1 transcript variants and molecular constitutive elements identifies novel cancer metastatic and prognostic biomarkers.

BACKGROUND: Abelson interactor 1 (ABI1) is associated with the metastasis and prognosis of many malignancies. The association between ABI1 transcript spliced variants, their molecular constitutive exons and exon-exon junctions (EEJs) in 14 cancer types and clinical outcomes remains unsolved. OBJECTIVE: To identify novel cancer metastatic and prognostic biomarkers from ABI1 total mRNA, TSVs, and molecular constitutive elements. METHODS: Using data from TCGA and TSVdb database, the standard median of ABI1 total mRNA, TSV, exon, and EEJ expression was used as a cut-off value. Kaplan-Meier analysis, Chi-squared test (X2) and Kendall's tau statistic were used to identify novel metastatic and prognostic biomarkers, and Cox regression analysis was performed to screen and identify independent prognostic factors. RESULTS: A total of 35 ABI1-related factors were found to be closely related to the prognosis of eight candidate cancer types. A total of 14 ABI1 TSVs and molecular constitutive elements were identified as novel metastatic and prognostic biomarkers in four cancer types. A total of 13 ABI1 molecular constitutive elements were identified as independent prognostic biomarkers in six cancer types. CONCLUSIONS: In this study, we identified 14 ABI1-related novel metastatic and prognostic markers and 21 independent prognostic factors in total 8 candidate cancer types.

Identification of AP002498.1 and LINC01871 as prognostic biomarkers and therapeutic targets for distant metastasis of colorectal adenocarcinoma.

BACKGROUND: Increasing evidence suggests that lncRNA (Long non-coding RNA, lncRNA)-mediated ceRNA (competing endogenous RNA, ceRNA) networks are involved in the occurrence and progression of colorectal cancer (CRC). However, the roles of the lncRNA-miRNA-mRNA ceRNA network in distant metastasis of CRC are still unclear. METHODS: In this study, we constructed a specific ceRNA network to identify potential biomarkers and therapeutic targets for distant metastasis of CRC. Specifically, RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to screen for differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) related to metastasis. After validation and selection by qRT-PCR and univariate and multivariate analysis of the metastasis- and prognosis-related lncRNAs, the regulated microRNAs (miRNAs) and coexpressed mRNAs were used to construct a ceRNA network for distant metastasis of CRC. RESULTS: Two key distant metastasis-related DElncRNAs, AP002498.1 and LINC01871, were identified by univariate and multivariate analysis in combination with analyses of clinical data and expression levels. Furthermore, lncRNA-associated ceRNA subnetworks were constructed from the predicted miRNAs and 13 coexpressed DEmRNAs (SERPINA1, ITLN1, REG4, L1TD1, IGFALS, MUC5B, CIITA, CXCL9, CXCL10, GBP4, GNLY, IDO1, and NOS2). The AP002498.1- and LINC01871-associated ceRNA subnetworks regulated the expression of the target genes SERPINA1 and MUC5B and GNLY, respectively, through the associated miRNAs. CONCLUSION: The DElncRNA AP002498.1 and the LINC01871/miR-4644 and miR-185-5p/GNLY axes were identified as being closely associated with distant metastasis and could represent independent prognostic biomarkers or therapeutic targets in colorectal adenocarcinoma.

Efficacy of a self-management program on quality of life in colorectal cancer patients: A randomized controlled trial.

PURPOSE: To test the efficacy of a self-management program based on acceptance and commitment therapy on quality of life, emotional distress, fatigue, physical activity, and fruit and vegetable intake in patients with colorectal cancer. METHODS: The study was a randomized controlled trial. A sample of 156 patients with colorectal cancer (stage I-III) was recruited by convenience sampling and participants were allocated randomly assigned to control or intervention groups. The intervention included a colorectal cancer self-management information booklet, two personal skills training sessions, and 12 follow-up telephone calls. The control group received health education leaflets. Outcome variables were assessed in both groups at baseline and every two months thereafter during the six-month follow-up period. RESULT: The mean age of participants was 62 years (range: 30-89 years). Generalized estimation equations analyses revealed significant differences over time in changes in anxiety (ß = -2.22, p = 0.001), depression (ß = -1.48, p = 0.033), fatigue (ß = 4.46, p = 0.001), physical and functional measures (ß = 6.16, p = 0.005), and colorectal-cancer-specific quality of life (ß = 7.45, p = 0.012). However, there were no significant differences in changes in physical activity or fruit and vegetable intake over time. CONCLUSION: The self-management skills provided by oncology nurses, including symptom management, psychological adjustment, and relaxation exercises, help colorectal cancer patients to overcome the challenges of cancer survivorship, accelerate their recovery, and improve their quality of life. THE TRIAL NUMBER: NCT03853278 registered on ClinicalTrials.gov.

Establishment of quantitative nested-PCR of Abelson interactor 1 transcript variant-11.

Abelson interactor 1 (ABI1), which presents 18 Transcript Variants (TSV), plays an important role in CRC metastasis. Different ABI1-TSVs play synergistic or antagonistic roles in the same pathophysiological events. ABI1 Transcript Variant-11 (ABI1-TSV-11) functionally promotes lymph node metastasis of left-sided colorectal cancer (LsCC) and is an independent molecular marker to evaluate the prognosis of patients with LsCC. However, there is still lack of a quick and accurate method to detect the expression of ABI-TSV-11, distinguishing ABI1-TSV-11 from other 17 TSVs. To establish a rapid method specific for ABI1-TSV-11detection, we developed a quantitative nested-PCR method composed of pre-amplification regular PCR using ABI1 universal primer pair and the followed Real Time (RT)-qPCR using ABI1-TSV-11 specific primer pair spanning exon-exon junction. ABI1-TSV-11-overexpressed SW480 and LoVo cell lines were used to verify the quantitative nested-PCR assay, and the sequencing data was used to evaluate the accuracy of ABI1-TSV-11 quantitative nested-PCR assay. The detection limit was 5.24×104 copies/ml. ABI1-TSV-11 quantitative nested-PCR provides a new technical means for the detection of ABI1-TSV-11.

Psychosocial Adjustment Changes and Related Factors in Postoperative Oral Cancer Patients: A Longitudinal Study.

Disease and treatment-related symptoms and dysfunctions can interfere with the psychosocial adjustment of patients with oral cancer. Identifying factors influencing psychosocial maladjustment is important because at-risk individuals can be targeted for early intervention. This prospective longitudinal study investigated psychosocial adjustment changes and associated factors in postoperative oral cancer patients. Data on psychosocial adjustment, facial disfigurement, symptoms, and social support were collected before surgery (T1) at one month (T2), three months (T3), and five months after discharge (T4). Fifty subjects completed the study, and their data were included in the analysis. Psychosocial maladjustment was reported in 50%, 59.2%, 66%, and 62% of subjects at T1, T2, T3, and T4, respectively. The subjects' psychosocial adjustment deteriorated after surgery. Results from generalized estimating equations indicated that financial status, cancer stage, pain, speech problems, social eating problems, and less sexuality were significant predictors of changes in psychosocial adjustment. Patients with insufficient income, stage III/IV cancer, severe pain, speech problems, social eating problems, and less sexuality were at higher risk for postoperative psychosocial maladjustment. Continued psychosocial assessment and appropriate supportive measures are needed to strengthen the psychosocial adjustment of these high-risk groups.

Factors Influencing Sleep Quality in Open-Heart Patients in the Postoperative Intensive Care Unit.

Open-heart patients often experience sleep problems postoperatively. This cross-sectional study is aimed to investigate open-heart patients' sleep quality and its influencing factors during intensive care. A consecutive sample of 117 eligible open-heart patients was recruited from an intensive care unit (ICU) of a general hospital. Data were collected using questionnaires. The respondents were 22-88 years, with a median age of 60.25 (13.51). Seventy-nine (67.5%) respondents were male. Most respondents reported a low-to-moderate postoperative pain level (average pain score = 2.02; range: 0-10). The average anxiety score was 4.68 (standard deviation [SD] = 4.2), and the average depression score was 6.91 (SD = 4.52; range: 0-21). The average sleep efficiency index was 70.4% (SD = 10.74%). Most (95.7%) respondents had a sleep efficiency index below 85%, indicating that most patients did not sleep well in the ICU. Linear regression analysis showed that the key predictors of the sleep quality of open-heart patients in the ICU were wound pain (ß = -1.9) and noise disturbance (ß = -1.86). These results provide information on sleep quality and the factors affecting postoperative patients in the ICU. These findings can be used as a reference for developing relevant interventions.

Effect of Oral Exercise on Trismus after Oral Cancer Radiotherapy: A Quasi-Experimental Study.

Trismus is a severe complication of oral cancer treatment. Oral exercise is a potentially helpful approach for preventing or improving trismus. The study aimed to test the efficacy of an oral exercise for enhancing the maximum inter-incisal opening (MIO) in patients undergoing surgery and radiotherapy for oral cancer. This is a quasi-experimental study. A sample of 69 oral cancer patients completed the study, with 35 in the control group and 34 in the intervention group. Intervention subjects were asked to perform three 20-min oral exercise sessions per day for six months. Data on oral exercise practicing time, MIO, and mandibular function impairment were collected at the last radiotherapy exposure (T1), three months (T2), and six months (T3) after the radiotherapy. At T3, the intervention group exercised 217.1 min (95%CI: 107.4~326.7) more than the control group. The generalized estimation equations showed a statistically significant group-by-time interaction in MIO. The change in MIO score from T1 to T3, as indicated by the regression slope, was 2.5 mm (95%CI: 0.4~4.6) greater in the intervention group than in the control group. The results support the efficacy of the study intervention for improving patient exercise adherence and MIO.

Nutritional Status and Related Factors in Patients with Gastric Cancer after Gastrectomy: A Cross-Sectional Study.

Patients after gastrectomy for gastric cancer are at risk of malnutrition, and poor nutritional status negatively affects patients' clinical outcomes. Knowledge of the factors influencing patients' nutritional status can inform interventions for improving patients' nutrition. A cross-sectional study was conducted to describe nutritional status and related factors in gastric cancer patients after gastrectomy. A convenience sample of gastric cancer patients with gastrectomy was recruited from general surgery or oncology clinics of a medical center in northern Taiwan. Data were collected with self-reported questionnaires, including the Functional Assessment Cancer Therapy­Gastric Module version 4, the Concerns in Meal Preparation scale, the Center for Epidemiologic Studies Depression Scale, and the Mini Nutrition Assessment. One hundred and one gastric cancer patients participated in the study. There were 81 cases of subtotal gastrectomy and 20 cases of total gastrectomy. Most patients (52.5%) were malnourished or at risk. Linear regression showed that symptom severity (ß = −0.43), employment status (ß = 0.19), and difficulty in diet preparation (ß = −0.21) were significant predictors of nutritional status. Together, these three variables explained 35.8% of the variance in patient nutritional status (F = 20.3, p < 0.001). More than 50% of our participants were malnourished or at risk for malnutrition, indicating a need for continued monitoring and support after discharge from hospitals. Special attention should be given to patients with severe symptoms, unemployment, and difficulties in diet preparation.

Cell cycle arrest is an important mechanism of action of compound Kushen injection in the prevention of colorectal cancer.

Compound Kushen injection (CKI) is the most widely used traditional Chinese medicine preparation for the comprehensive treatment of colorectal cancer (CRC) in China, but its underlying molecular mechanisms of action are still unclear. The present study employed a network pharmacology approach, in which we constructed a "bioactive compound-target-pathway" network. Experimental RNA sequencing (RNA-Seq) analysis was performed to identify a key "bioactive compound-target-pathway" network for subsequent experimental validation. Cell cycle, proliferation, autophagy, and apoptosis assays and a model of azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis in mice were employed to detect the biological effect of CKI on CRC. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were performed to verify the selected targets and pathways. We constructed a predicted network that included 82 bioactive compounds, 34 targets, and 33 pathways and further screened an anti-CRC CKI "biological compound (hesperetin 7-O-rutinoside, genistein 7-O-rutinoside, and trifolirhizin)-target (p53 and checkpoint kinase 1 [CHEK1])" network that targeted the "cell cycle pathway". Validation experiments showed that CKI effectively induced the cell-cycle arrest of CRC cells in vitro and suppressed the development of CRC in vivo by downregulating the expression of p53 and CHEK1. Our findings confirmed that inducing cell-cycle arrest by CKI is an important mechanism of its anti-CRC action, which provides a direct and scientific experimental basis for the clinical application of CKI.

Exercise Experiences of Older Adults with Diabetes and Sarcopenia: A Phenomenological Study.

Sarcopenia is a common and progressive skeletal muscle condition, often described as an intermediate stage in the development of frailty and disability in patients with diabetes. This can be improved through physical activity and exercise. This descriptive phenomenological study explored the exercise experiences of older adults with diabetes and sarcopenia. Individual interviews were conducted following semi-structured interview guidelines, and narratives were analyzed using Giorgi's method. Data saturation was achieved after interviewing 14 purposively sampled older patients with diabetes and sarcopenia. The study identified three main themes: encountering difficulty during exercise, recognizing the advantages of exercise, and constructing a suitable exercise model. While older adults with diabetes and sarcopenia may encounter difficulty during exercise, they also experience positive feedback from exercise. Understanding the limitations of older adults, individualizing exercise models based on their exercise experiences, and providing appropriate interventions and necessary emotional support can effectively prevent diabetes and sarcopenia.

Abelson interactor 1 splice isoform-L plays an anti-oncogenic role in colorectal carcinoma through interactions with WAVE2 and full-length Abelson interactor 1.

BACKGROUND: Expression of the full-length isoform of Abelson interactor 1 (ABI1), ABI1-p65, is increased in colorectal carcinoma (CRC) and is thought to be involved in one or more steps leading to tumor progression or metastasis. The ABI1 splice isoform-L (ABI1-SiL) has conserved WAVE2-binding and SH3 domains, lacks the homeo-domain homologous region, and is missing the majority of PxxP- and Pro-rich domains found in full-length ABI1-p65. Thus, ABI1-SiL domain structure suggests that the protein may regulate CRC cell morphology, adhesion, migration, and metastasis via interactions with the WAVE2 complex pathway. AIM: To investigate the potential role and underlying mechanisms associated with ABI1-SiL-mediated regulation of CRC. METHODS: ABI1-SiL mRNA expression in CC tissue and cell lines was measured using both qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR. A stably ABI1-SiL overexpressing SW480 cell model was constructed using Lipofectamine 2000, and cells selected with G418. Image J software, CCK8, and transwell assays were used to investigate SW480 cell surface area, proliferation, migration, and invasion. Immunoprecipitation, Western blot, and co-localization assays were performed to explore intermolecular interactions between ABI1-SiL, WAVE2, and ABI1-p65 proteins. RESULTS: ABI1-SiL was expressed in normal colon tissue and was significantly decreased in CRC cell lines and tissues. Overexpression of ABI1-SiL in SW480 cells significantly increased the cell surface area and inhibited the adhesive and migration properties of the cells, but did not alter their invasive capacity. Similar to ABI1-p65, ABI1-SiL still binds WAVE2, and the ABI1-p65 isoform in SW480 cells. Furthermore, co-localization assays confirmed these intermolecular interactions. CONCLUSION: These results support a model in which ABI1-SiL plays an anti-oncogenic role by competitively binding to WAVE2 and directly interacting with phosphorylated and non-phosphorylated ABI1-p65, functioning as a dominant-negative form of ABI1-p65.

The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer.

Abnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

Comprehensive analysis of ceRNA networks reveals prognostic lncRNAs related to immune infiltration in colorectal cancer.

BACKGROUND: Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis. METHODS: RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm. RESULTS: A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types. CONCLUSIONS: MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma.

Study Effects of Drug Treatment and Physiological Physical Stimulation on Surfactant Protein Expression of Lung Epithelial Cells Using a Biomimetic Microfluidic Cell Culture Device.

This paper reports a biomimetic microfluidic device capable of reconstituting physiological physical microenvironments in lungs during fetal development for cell culture. The device integrates controllability of both hydrostatic pressure and cyclic substrate deformation within a single chip to better mimic the in vivo microenvironments. For demonstration, the effects of drug treatment and physical stimulations on surfactant protein C (SPC) expression of lung epithelial cells (A549) are studied using the device. The experimental results confirm the device's capability of mimicking in vivo microenvironments with multiple physical stimulations for cell culture applications. Furthermore, the results indicate the critical roles of physical stimulations in regulating cellular behaviors. With the demonstrated functionalities and performance, the device is expected to provide a powerful tool for further lung development studies that can be translated to clinical observation in a more straightforward manner. Consequently, the device is promising for construction of more in vitro physiological microenvironments integrating multiple physical stimulations to better study organ development and its functions.

Paddlewheel SBU based Zn MOFs: Syntheses, Structural Diversity, and CO2 Adsorption Properties.

Four Zn metal⁻organic frameworks (MOFs), {[Zn2(2,6-ndc)2(2-Pn)]·DMF}n (1), {[Zn2(cca)2(2-Pn)]·DMF}n (2), {[Zn2(thdc)2(2-Pn)]·3DMF}n (3), and {[Zn2(1,4-ndc)2(2-Pn)]·1.5DMF}n (4), were synthesized from zinc nitrate and N,N'-bis(pyridin-2-yl)benzene-1,4-diamine (2-Pn) with naphthalene-2,6-dicarboxylic acid (2,6-H2ndc), 4-carboxycinnamic acid (H2cca), 2,5-thiophenedicarboxylic acid (H2thdc), and naphthalene-1,4-dicarboxylic acid (1,4-H2ndc), respectively. MOFs 1⁻4 were all constructed from similar dinuclear paddlewheel {Zn2(COO)4} clusters and resulted in the formation of three kinds of uninodal 6-connected non-interpenetrated frameworks. MOFs 1 and 2 suit a topologic 48·67-net with 17.6% and 16.8% extra-framework voids, respectively, 3 adopts a pillared-layer open framework of 48·66·8-topology with sufficient free voids of 39.9%, and 4 features a pcu-type pillared-layer framework of 412·6³-topology with sufficient free voids of 30.9%. CO2 sorption studies exhibited typical reversible type I isotherms with CO2 uptakes of 55.1, 84.6, and 64.3 cm³ g-1 at 195 K and P/P0 =1 for the activated materials 1', 2', and 4', respectively. The coverage-dependent isosteric heat of CO2 adsorption (Qst) gave commonly decreased Qst traces with increasing CO2 uptake for all the three materials and showed an adsorption enthalpy of 32.5 kJ mol-1 for 1', 38.3 kJ mol-1 for 2', and 23.5 kJ mol-1 for 4' at zero coverage.