Associations between preparedness, perceived stress, depression, and quality of life in family caregivers of patients with a temporary enterostomy.

PURPOSE: To investigate the preparedness, perceived stress, risk of depression, and quality of life of family caregivers of patients receiving a temporary enterostomy, to provide a reference for improving the long-term care and quality of life of patients receiving a temporary enterostomy. METHODS: We enrolled 181 family caregivers of patients in a hospital in China from 2021 to 2023. Responses to the General Information Questionnaire, the Chinese Caregiver Preparedness Scale, the Chinese Perceived Stress Scale, the Chinese bilingual version of the Patient Health Questionnaire-2, and the 12-item Short Form Survey were collected online. RESULTS: Pearson's correlation analysis revealed that family caregivers' risk of depression was negatively correlated with their preparedness, the physical component summary score, and the mental component summary score but was positively correlated with perceived stress. Multiple linear regression analysis identified factors influencing caregiver preparedness. CONCLUSIONS: These findings help healthcare personnel to identify high-risk individuals among family caregivers of patients receiving a temporary enterostomy. This provides a basis for formulating well-planned, dynamic health education programs that meet patients' needs for disease-related knowledge and care.

The effects of a nurse-led discharge planning on the health outcomes of colorectal cancer patients with stomas: A randomized controlled trial.

BACKGROUND: Nursing care of colorectal cancer patients with stomas presents unique challenges, particularly during the transition from hospital to home. Early discharge programs can assist patients during this critical period. However, the effects of delivering a nurse-led discharge planning program remain under-studied. OBJECTIVE: Evaluate the effects of a nurse-led discharge planning on the quality of discharge education, stoma self-efficacy, readiness for hospital discharge, stoma quality of life, incidence of stoma complications, unplanned readmission rate, and length of stays. DESIGN: Assessor-blind parallel-arm randomized controlled trial with a repeated-measures design. SETTING(S): Participants were recruited from inpatients in the colorectal surgery unit of a university-affiliated hospital in Fujian, China. PARTICIPANTS: A total of 160 patients with colorectal cancer who received enterostomy surgery and were scheduled to be discharged to their homes. METHOD: Participants were randomly allocated to the experimental and control groups. The former received nurse-led discharge planning in addition to the usual discharge education, while the control group received only the usual discharge education. The program included an assessment, health education, stoma care, stoma support, discharge review, discharge medication and checklist integration, discharge referral, and post-hospital follow-up. Baseline data were collected prior to the intervention (T0). Data on the quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, and stoma quality of life were measured on the day of discharge from the hospital (T1). Patients' stoma self-efficacy and quality of life were repeat-measured 30 (T2) and 90 days post-discharge (T3). Data on stoma complications (T1, T2, T3), length of stays (T1), and unplanned readmission (T2, T3) were collected from medical records. RESULTS: Participants in the intervention group showed significant improvement in the quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, stoma quality of life, complications, and unplanned readmission, compared to the control group (p < 0.001). However, no statistically significant differences were observed in length of stays (p > 0.05). CONCLUSIONS: The program was effective for improving quality of discharge teaching, readiness for hospital discharge, stoma self-efficacy, and stoma quality of life, as well as for reducing complications and unplanned readmission among stoma patients. Integration of discharge planning into the usual process of care is recommended for clinical practice to facilitate a successful transition from hospital to home. REGISTRATION: This study was registered at the Chinese clinical trial registry (ChiCTR2200058756) on April 16, 2022, and participant recruitment was initiated in May 2022.

Risk of temporal lobe necrosis between proton beam and volumetric modulated arc therapies in patients with different head and neck cancers.

BACKGROUND: To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. METHODS: We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. RESULTS: Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70). CONCLUSION: Our study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.

Effects of Psycho-education Interventions on Colorectal Cancer Patients: A systematic review and meta-analysis.

Colorectal cancer (CRC) patients not only undergo physical symptoms but also psychological suffering. Psycho-education interventions have been implemented widely to improve their psychological well-being. However, the effectiveness of psycho-education is unclear. Therefore, this research evaluates the effectiveness of psycho-education interventions on CRC patient outcomes and identifies effective intervention characteristics. The researchers searched the following databases: PubMed, Embase, PsycINFO, Cochrane, Medline, Web of Science, CINAHL, ProQuest, Wan Fang Data, Chinese National Knowledge Infrastructure, Chinese Biomedicine Database, and China Academic Journals Full-Text Database. Additionally, gray literature and bibliographies of the included studies were also searched. Finally, this review included 11 randomized controlled trials and one controlled clinical trial. The results showed that psycho-education interventions exerted positive impacts on relieving anxiety and depression, improving self-efficacy and quality of life for CRC patients either immediately, post-intervention, or at least 2 months after intervention. Despite the variety of psycho-education interventions, health education, stress management, coping skills training, and social support are also essential components. Future research should include multi-center studies with sufficient sample sizes and rigorous designs.

Detection of the gene mutation of epidermal growth factor receptor in lung adenocarcinoma by radiomic features from a small amount of PET data.

OBJECTIVE: The purpose of this work was to identify the potential mutation of epidermal growth factor receptor in nonsmall cell adenocarcinoma by noninvasive method, and to explore whether the same or better effect can be achieved using a small amount of single-mode PET image data. METHOD: A total of 115 patients were recruited and the results of their 18F-FDG PET images and gene detection after resection were obtained; 117 original radiation features and 744 wavelet transform features were extracted from PET images. Several methods were used to reduce the dimension of the data, and four classifier models were established to classify it. The above process was repeated to reduce the total amount of data and the area under the receiver operating characteristic curve (AUC) value that changed with the reduction of the data and the stability of the results was recorded. RESULTS: The classifier with the best comprehensive performance under this dataset was logistic regression, whose AUC value is 0.843. And similar results can be obtained from only 30 cases of data. CONCLUSION: A similar or better result could be achieved using a small number of single-mode PET images. In addition, significant results could be obtained using only the PET images of 30 patients.

Radiomics nomogram for the prediction of microvascular invasion of HCC and patients' benefit from postoperative adjuvant TACE: a multi-center study.

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.

Applications of radiomics-based analysis pipeline for predicting epidermal growth factor receptor mutation status.

BACKGROUND: This study aimed to develop a pipeline for selecting the best feature engineering-based radiomic path to predict epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). METHODS: The study enrolled 115 lung adenocarcinoma patients with EGFR mutation status from June 2016 and September 2017. We extracted radiomics features by delineating regions-of-interest around the entire tumor in 18F-FDG PET/CT images. The feature engineering-based radiomic paths were built by combining various methods of data scaling, feature selection, and many methods for predictive model-building. Next, a pipeline was developed to select the best path. RESULTS: In the paths from CT images, the highest accuracy was 0.907 (95% confidence interval [CI]: 0.849, 0.966), the highest area under curve (AUC) was 0.917 (95% CI: 0.853, 0.981), and the highest F1 score was 0.908 (95% CI: 0.842, 0.974). In the paths based on PET images, the highest accuracy was 0.913 (95% CI: 0.863, 0.963), the highest AUC was 0.960 (95% CI: 0.926, 0.995), and the highest F1 score was 0.878 (95% CI: 0.815, 0.941). Additionally, a novel evaluation metric was developed to evaluate the comprehensive level of the models. Some feature engineering-based radiomic paths obtained promising results. CONCLUSIONS: The pipeline is capable of selecting the best feature engineering-based radiomic path. Combining various feature engineering-based radiomic paths could compare their performances and identify paths built with the most appropriate methods to predict EGFR-mutant lung adenocarcinoma in 18FDG PET/CT. The pipeline proposed in this work can select the best feature engineering-based radiomic path.

Preoperative determination of pathological grades of primary single HCC: development and validation of a scoring model.

PURPOSE: This study aimed to establish a reliable diagnostic score model for the preoperative determination of pathological grade in HCC based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI and biochemical indicators. METHODS: In this retrospective study, we analyzed 139 patients with HCC who underwent Gd-EOB-DTPA MRI between 2014 and 2020, including an establishment cohort of 76 patients and a validation cohort of 63 patients. Based on the imaging features demonstrated on Gd-EOB-DTPA MRI images and biochemical indicators of the establishment cohort, a scoring model based on logistic regression was developed, and compared with postoperative pathological findings in terms of effective determination of pathological grade. The validity of the scoring model was assessed by ROC curves and an independent external validation cohort. RESULTS: Three parameters related to pathological grades were identified, including maximum diameter of the tumor, peritumoral hypointensity in the hepatobiliary phase, and [alkaline phosphatase (U/L) + gamma glutamyl transpeptidase (U/L)]/ lymphocyte count (× 109/L) (AGLR) ratios. Based on these three parameters, a scoring model was developed. ROC curve showed that a score of > 5 was set as the threshold for determining pathological grades with accuracy, sensitivity, specificity, PPV, and NPV of 89.5%, 75.0%, 95.1%, 85.7%, and 90.7%, respectively. CONCLUSION: The study provided the groundwork for a promising and easily implementable scoring model for preoperative determination of HCC pathological grades, for which further validation should be pursued.

Effects of Mindfulness-Based Therapy for Cancer Patients: A Systematic Review and Meta-analysis.

This meta-analysis was a systematic review of evidence on the effects of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on quality of life (QOL), pain, fatigue, anxiety, and depression in cancer patients. Until July 2020, PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs). The study included 18 RCTs. The MBSR/MBCT intervention resulted in a significant effect on QOL (SMD 0.80, CI 0.28, 1.32, I2 = 94%). In subgroup analysis, MBSR/MBCT interventions had a significant effect in the early cancer stage on anxiety (SMD - 3.48, CI - 4.07, - 2.88), and QOL (SMD 4.30, CI 3.62, 4.99); in alleviating decreasing pain (SMD - 0.42, CI - 0.70, - 0.14) within 4 weeks after the end of intervention, and alleviating fatigue in younger participants (SMD - 0.64, CI - 1.09, - 0.19). MBSR/MBCT has short-term effects on cancer patients, especially in younger patients and early cancer stages.

Optimization of Class I Histone Deacetylase PROTACs Reveals that HDAC1/2 Degradation is Critical to Induce Apoptosis and Cell Arrest in Cancer Cells.

Class I histone deacetylase (HDAC) enzymes 1, 2, and 3 organize chromatin as the catalytic subunits within seven distinct multiprotein corepressor complexes and are established drug targets. We report optimization studies of benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTACs) and for the first time describe transcriptome perturbations resulting from these degraders. By modifying the linker and VHL ligand, we identified PROTACs 7, 9, and 22 with submicromolar DC50 values for HDAC1 and/or HDAC3 in HCT116 cells. A hook effect was observed for HDAC3 that could be negated by modifying the position of attachment of the VHL ligand to the linker. The more potent HDAC1/2 degraders correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells. We demonstrate that HDAC1/2 degradation by PROTACs correlates with enhanced global gene expression and apoptosis, important for the development of more efficacious HDAC therapeutics with reduced side effects.

5-Lipoxygenase promotes epithelial-mesenchymal transition through the ERK signaling pathway in gastric cancer.

BACKGROUND AND AIM: 5-Lipoxygenase has been reported to enhance cell proliferation, migration, and invasion. Epithelial-mesenchymal transition is considered an important process for tumor metastasis and invasion. METHODS: The 5-lipoxygenase expression levels and the prognoses in patients with gastric cancer were evaluated by immunohistochemistry and by the log-rank test on Kaplan-Meier curves. We established 5-lipoxygenase-overexpressed and 5-lipoxygenase-silenced gastric cancer cells and measured migration, invasion, and epithelial-mesenchymal transition makers to examine the role of 5-lipoxygenase in gastric cancer in vitro. In vivo, 5-lipoxygenase-overexpressed gastric cancer cells were administered into mice by subcutaneous injection, intraperitoneal injection or splenic intravenous injection to study the proliferation or metastasis of 5-lipoxygenase in mice. Using the extracellular signal-regulated kinase pathway inhibitor U0126 and activator tumor growth factor-ß, we investigated the mechanism of epithelial-mesenchymal transition induced by 5-lipoxygenase in gastric cancer cells. RESULTS: 5-Lipoxygenase was upregulated in gastric cancer tissues and was related to poor overall survival in gastric cancer patients. 5-Lipoxygenase promoted gastric cancer cell proliferation, migration, and invasion and induced the process of epithelial-mesenchymal transition in gastric cancer cells. In the nude mouse model, mice with gastric cancer tumors overexpressing 5-LOX had a faster tumor growth rate and more severe abdominal and liver metastases than the control group. Inhibition of extracellular signal-regulated kinase signaling by U0126 or activation by tumor growth factor-ß neutralized the effect of 5-LOX overexpression or silencing on epithelial-mesenchymal transition. CONCLUSION: 5-Lipoxygenase promotes epithelial-mesenchymal transition in gastric cancer by activating the extracellular signal-regulated kinase signaling pathway.

Early Activation of Myeloid-Derived Suppressor Cells Participate in Sepsis-Induced Immune Suppression via PD-L1/PD-1 Axis.

Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. Methods: The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect. Results: Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells. Conclusions: Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis.

LncRNA Expression Profiling in Advanced Resected Gastric Adenocarcinoma Tissues.

BACKGROUND: Long noncoding RNAs (lncRNAs) are the chief products of human transcriptomes and have a major function in mediating gene expression. Abnormal lncRNA levels have been detected in gastric cancer. However, changes in lncRNA expression in advanced gastric adenocarcinoma (GA) are largely unexplored. METHODS: We studied the expression of lncRNAs and mRNAs in 6 advanced resected GA (ARGA) tissues using a lncRNA microarray chip. RESULTS: Among 22,870 lncRNAs expressed in ARGA and paired nonneoplastic tissues (non-GA), 1,769 and 1,710 were up- or downregulated, respectively, in all 6 ARGA tissues (≥ 2.0-fold, p < 0.05). The expression of 5 differentially expressed lncRNAs, HNF1A-AS1, RP11-62F24.2, GAS5, MALAT1, and H19 were randomly selected to be measured in 47 patients using real-time quantitative reverse transcription PCR (qRT-PCR), and the data were consistent with those obtained from the microarray chip. Analysis of their nearby coding genes (mRNAs) revealed that the main associated GO (gene ontology) classes were genes that regulate cellular metabolic processes, protein binding and receptor binding, whereas the main associated pathways were MAPK signaling, which regulates cell proliferation and differentiation and the apoptosis pathway, which is cancer-related. Some (n = 37) differentially expressed lncRNAs had direct annotated functions; among these lncRNAs, 27 were associated with cancer, cancer pathways, oncogenes, and tumor suppressor genes and with cell development and differentiation. CONCLUSIONS: Expression differences in lncRNAs exist between advanced GA and noncancerous gastric tissues, so lncRNA expression patterns may explain gastric carcinogenesis and progression as well as serve as candidate biomarkers for the treatment of GA.

Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection.

BACKGROUND: The single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may also play a role in gastric adenocarcima (GA). METHODS: We genotyped the SLC39A6 rs1050631 in 512 patients who underwent GA resection. All study subjects lived in an area of China with high GA incidence. Genotypes were examined for possible correlation with survival and recurrence. The potential involvement of SLC39A6 in gastric cancer was explored in clinical samples and cell culture studies. RESULTS: Multivariable analysis showed that patients with the CT + TT genotype at SLC39A6 rs1050631 were at greater risk of recurrence (hazard ratio, HR 1.387, p = 0.004) and death (HR 1.429, p = 0.002) than patients with CC genotype. Median recurrence-free and overall survival were significantly shorter in patients with the CT + TT genotype (20, 27 months) than in patients with the CC genotype (36, 43 months, p = 0.001, p < 0.001). Patients with the CT + TT genotype who were male or ≥ 60 years, or who had a tumor ≥5 cm or a moderately differentiated tumor were at significantly higher risk of recurrence and death. SLC39A6 was overexpressed in tissues from GA patients and in GA cell lines, and SLC39A6 knockdown in GA cell lines inhibited their proliferation, migration and invasion. CONCLUSION: SLC39A6 rs1050631 correlates with post-resection prognosis of GA patients and SLC39A6 may participate in GA onset or progression.

ATGL promotes the proliferation of hepatocellular carcinoma cells via the p-AKT signaling pathway.

Abnormal metabolism, including abnormal lipid metabolism, is a hallmark of cancer cells. Some studies have demonstrated that the lipogenic pathway might promote the development of hepatocellular carcinoma (HCC). However, the role of adipose triglyceride lipase (ATGL) in hepatocellular carcinoma cells has not been elucidated. We evaluated the function of ATGL in hepatocellular carcinoma using methyl azazolyl blue and migration assay through overexpression of ATGL in HepG2 cells. Quantitative reverse-transcription polymerase chain reaction and Western blot analyses were used to assess the mechanisms of ATGL in hepatocellular carcinoma. In the current study, we first constructed and transiently transfected ATGL into hepatocellular carcinoma cells. Secondly, we found that ATGL promoted the proliferation of hepatoma cell lines via upregulating the phosphorylation of AKT, but did not affect the metastatic ability of HCC cells. Moreover, the p-AKT inhibitor significantly eliminated the effect of ATGL on the proliferation of hepatoma carcinoma cells. Taken together, our results indicated that ATGL promotes hepatocellular carcinoma cells proliferation through upregulation of the AKT signaling pathway.

lncRNA ATXN8OS promotes breast cancer by sequestering miR­204.

Breast cancer (BC) is a common malignancy among women and the leading cause of female cancer mortality worldwide. In recent years, increasing evidence has shown that long non­coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) in human cancer and that they are involved in many biological processes, including proliferation, migration, apoptosis and invasion. In the present study, the biological function and molecular mechanism of ataxin 8 opposite strand (ATXN8OS) in BC tissue and cell lines were investigated. It was found that ATXN8OS was markedly up­regulated in BC tissue and cell lines, and that its level of overexpression was inversely linked with the overall survival rate of patients with BC. Knockdown of ATXN8OS inhibited proliferation, viability and invasion in the human MCF7 and MDA­MB­231 BC cell lines. In addition, microRNA­204 (miR­204) was negatively associated with the expression of ATXN8OS in BC tissues and cell lines. A luciferase assay demonstrated a direct binding site for miR­204 within ATXN8OS, and inhibition of miR­204 stimulated the tumour­promoting effect of ATXN8OS on BC cells. In conclusion, the present study suggested that ATXN8OS acts as a tumour promoter by sequestering miR­204 during the development of BC, therefore providing a mechanistic insight which may facilitate the diagnosis and treatment of BC.

Aberrantly expressed miR-188-5p promotes gastric cancer metastasis by activating Wnt/ß-catenin signaling.

BACKGROUND: Gastric cancer (GC) is one of the most common human cancers with the high rate of recurrence, metastasis and mortality. Aberrantly expressed microRNAs (miRNAs) are associated with invasion and metastasis in various human cancers. Recently, miR-188-5p has been indicated as an oncogene in GC since it promotes GC cell growth and metastasis. However, the underlying molecular mechanism remains to be fully defined. METHODS: Using Significance Analysis of Microarrays (SAM) screening, we identified that miR-188-5p is associated with overall survival and lymph node metastasis in patients with GC. The functional impact of miR-188-5p on GC metastasis was validated using in vitro and in vivo assays. The regulatory function of miR-188-5p on Wnt/ß-catenin signaling activation through directly targeting PTEN was proven using quantitative real-time PCR, western blot analysis, a dual-luciferase assay, a Transwell assay, and immunofluorescence. Immunohistochemical analyses further confirmed the clinical significance of miR-188-5p in GC. RESULTS: MiR-188-5p diminishes tumor suppressor PTEN expression, and further increases phospho-Ser9 of GSK3ß to activate Wnt/ß-catenin signaling in GC. Consequently, miR-188-5p enhanced the migration and invasion of GC cells in vitro and tumor metastasis in vivo, whereas inhibition of miR-188-5p had the opposite effects. Moreover, miR-188-5p was negatively correlated with PTEN expression but positively correlated with nuclear ß-catenin staining in GC samples. CONCLUSIONS: Our findings revealed a model of the miR-188-5p-PTEN-ß-catenin axis in GC, which mediates the constitutive activation of Wnt/ß-catenin signaling and promotes tumor metastasis, inferring that miR-188-5p is a potential therapeutic target to treat GC.

Influence of facial threading on various physiological parameters of the skin: non-randomized trial involving adult women in Taiwan

Abstract: Background: Facial threading involves the removal of hairs to restore facial skin smoothness. However, its effectiveness has not been rigorously evaluated. Objective: To evaluate effects of facial threading on skin roughness, hydration, melanin index, and vellus hair on the face, complemented by a subjective evaluation of the tactile feel of the skin and improvement in skin color. Method: Participants who had not used exfoliators for two weeks before the experiment were included. Each participant underwent one session of facial threading every 21 days, for a total of 3 sessions. A three-dimensional skin roughness instrument and a multifunctional skin testing system were used to evaluate changes in roughness, hydration, and pigmentation on the forehead, cheeks, and corners of the mouth. A photomicrographic camera was used to record changes in vellus hair. Subjective reports of skin smoothness and color were recorded. Result: Eighteen participants completed the study. Facial threading produced a significant decrease in skin roughness on the forehead (22.42%, p = .013), right cheek (77%, p = .02), and left corner of the mouth (33.02%, p = .001). Subjective improvement in tactile feel of the skin and coloring were reported. Study Limitations: The study did not include randomization, with further limitations of a small sample size and a single site. Conclusion: Facial threading reduced skin roughness by 26.74% after three threading sessions, with improved subjective assessment of tactile feel and coloring. Future research should include a comparison with other cosmetic products with similar beautifying effects or a control group.

An Aspartate-Specific Solute-Binding Protein Regulates Protein Kinase G Activity To Control Glutamate Metabolism in Mycobacteria.

Signaling by serine/threonine phosphorylation controls diverse processes in bacteria, and identification of the stimuli that activate protein kinases is an outstanding question in the field. Recently, we showed that nutrients stimulate phosphorylation of the protein kinase G substrate GarA in Mycobacterium smegmatis and Mycobacterium tuberculosis and that the action of GarA in regulating central metabolism depends upon whether it is phosphorylated. Here we present an investigation into the mechanism by which nutrients activate PknG. Two unknown genes were identified as co-conserved and co-expressed with PknG: their products were a putative lipoprotein, GlnH, and putative transmembrane protein, GlnX. Using a genetic approach, we showed that the membrane protein GlnX is functionally linked to PknG. Furthermore, we determined that the ligand specificity of GlnH matches the amino acids that stimulate GarA phosphorylation. We determined the structure of GlnH in complex with different amino acid ligands (aspartate, glutamate, and asparagine), revealing the structural basis of ligand specificity. We propose that the amino acid concentration in the periplasm is sensed by GlnH and that protein-protein interaction allows transmission of this information across the membrane via GlnX to activate PknG. This sensory system would allow regulation of nutrient utilization in response to changes in nutrient availability. The sensor, signaling, and effector proteins are conserved throughout the Actinobacteria, including the important human pathogen Mycobacterium tuberculosis, industrial amino acid producer Corynebacterium glutamicum, and antibiotic-producing Streptomyces species.IMPORTANCE Tuberculosis (TB) kills 5,000 people every day, and the prevalence of multidrug-resistant TB is increasing in every country. The processes by which the pathogen Mycobacterium tuberculosis senses and responds to changes in its environment are attractive targets for drug development. Bacterial metabolism differs dramatically between growing and dormant cells, and these changes are known to be important in pathogenesis of TB. Here, we used genetic and biochemical approaches to identify proteins that allow M. tuberculosis to detect amino acids in its surroundings so that it can regulate its metabolism. We have also shown how individual amino acids are recognized. The findings have broader significance for other actinobacterial pathogens, such as nontuberculous mycobacteria, as well as Actinobacteria used to produce billions of dollars of amino acids and antibiotics every year.