Construction and Analysis of a Mitochondrial Metabolism-Related Prognostic Model for Breast Cancer to Evaluate Survival and Immunotherapy.

As one of the most prevalent malignancies among women, breast cancer (BC) is tightly linked to metabolic dysfunction. However, the correlation between mitochondrial metabolism-related genes (MMRGs) and BC remains unclear. The training and validation datasets for BC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. MMRG-related data were obtained from the Molecular Signatures Database. A risk score prognostic model incorporating MMRGs was established based on univariate, LASSO, and multivariate Cox regression analyses. Independent factors affecting BC prognosis were identified through regression analysis and presented in a nomogram. Single-sample gene set enrichment analysis was employed to assess the immune levels of high-risk (HR) and low-risk (LR) groups. The sensitivity of BC patients in the two groups to common anti-tumor drugs was evaluated by utilizing the Genomics of Drug Sensitivity in Cancer database. 12 MMRGs significantly associated with survival were selected from 1234 MMRGs. A 12-gene risk score prognostic model was built. In the multivariate regression analysis incorporating classical clinical factors, the MMRG-related risk score remained an independent prognostic factor. As revealed by tumor immune microenvironment analysis, the LR group with higher survival rates had elevated immune levels. The drug sensitivity results unmasked that the LR group demonstrated higher sensitivity to Irinotecan, Nilotinib, and Oxaliplatin, while the HR group demonstrated higher sensitivity to Lapatinib. The development of MMRG characteristics provides a comprehensive understanding of mitochondrial metabolism in BC, aiding in the prediction of prognosis and tumor microenvironment, and offering promising therapeutic choices for BC patients with different MMRG risk scores.

Aberrant brain intra- and internetwork functional connectivity in children with Prader-Willi syndrome.

PURPOSE: Prader-Willi syndrome (PWS) suffers from brain functional reorganization and developmental delays during childhood, but the underlying neurodevelopmental mechanism is unclear. This paper aims to investigate the intra- and internetwork functional connectivity (FC) changes, and their relationships with developmental delays in PWS children. METHODS: Resting-state functional magnetic resonance imaging datasets of PWS children and healthy controls (HCs) were acquired. Independent component analysis was used to acquire core resting-state networks (RSNs). The intra- and internetwork FC patterns were then investigated. RESULTS: In terms of intranetwork FC, children with PWS had lower FC in the dorsal attention network, the auditory network, the medial visual network (VN) and the sensorimotor network (SMN) than HCs (FWE-corrected, p < 0.05). In terms of internetwork FC, PWS children had decreased FC between the following pairs of regions: posterior default mode network (DMN) and anterior DMN; posterior DMN and SMN; SMN and posterior VN and salience network and medial VN (FDR-corrected, p < 0.05). Partial correlation analyses revealed that the intranetwork FC patterns were positively correlated with developmental quotients in PWS children, while the internetwork FC patterns were completely opposite (p < 0.05). Intranetwork FC patterns showed an area under the receiver operating characteristic curve of 0.947, with a sensitivity of 96.15% and a specificity of 81.25% for differentiating between PWS and HCs. CONCLUSION: Impaired intra- and internetwork FC patterns in PWS children are associated with developmental delays, which may result from neural pathway dysfunctions. Intranetwork FC reorganization patterns can discriminate PWS children from HCs. REGISTRATION NUMBER ON THE CHINESE CLINICAL TRAIL REGISTRY: ChiCTR2100046551.

SCARA5 as a downstream factor of PCAT29, inhibits proliferation, migration, and invasion of bladder cancer.

Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.

Effect of laparoscopic versus open surgery on postoperative wound complications in patients with low rectal cancer: A meta-analysis.

This meta-analysis was conducted to evaluate the effect of microinvasive and open operations on postoperative wound complications in low rectal carcinoma patients. Research on limited English has been conducted systematically in PubMed, Embase, Cochrane Library and Web of Science. The date up to the search was in August 2023. Following review of the classification and exclusion criteria for this research and the evaluation of its quality in the literature, there were a total of 266 related papers, which were reviewed for inclusion in the period from 2004 to 2017. A total of 1774 cases of low rectal cancer were enrolled. Of these 913 cases, the laparoscopic operation was performed on 913 cases, while 861 cases were operated on low rectal carcinoma. The overall sample was between 10 and 482. Five trials described the efficacy of laparoscopy have lower risk than open on postoperative wound infection in patients with low rectal cancer (OR, 0.72;95 % CI, 0.48,1.09 p = 0.12). Three studies results showed that the anastomotic leak was not significantly different between open and laparoscopy (OR, 0.86; 95% CI, 0.58,1.26 p = 0.44). Six surgical trials in low rectal cancer patients reported haemorrhage, and five cases of surgical time were reported, with laparoscopy having fewer bleeding compared with open surgery (MD, -188.89; 95% CI, -341.27, -36.51 p = 0.02). Compared with laparoscopy, the operation time was shorter for the open operation (MD, 33.06; 95% CI, 30.56, 35.57 p < 0.0001). Overall, there is no significant difference between laparoscopy and open surgery in terms of incidence of infection and anastomosis leak. However, the rate of haemorrhage in laparoscopy is lower，and operation time in open surgery is lower.

Impact of ileostomy on postoperative wound complications in patients after laparoscopic rectal cancer surgery: A meta-analysis.

To prevent anastomotic leakage and other postoperative complications after laparoscopic rectal cancer surgery, a protective ileostomy is often used. However, the necessity of performing ileostomy after laparoscopic rectal cancer remains controversial. The aim of this meta-analysis was to assess the benefit of ileostomy on wound infection after laparoscopic rectal cancer. The Cochrane Library, EMBASE, Web of Science, and PubMed were used to retrieve all related documents up to September 2023. Completion of the trial literature was submitted once the eligibility and exclusion criteria were met and the literature quality assessment was evaluated. This study compared the post-operative post-operative complications of an ileostomy with that of non-ileostomy in a laparoscope. We used Reman 5.3 to analyse meta-data. Controlled studies were evaluated with ROBINS-I. The meta-analyses included 525 studies, and 5 publications were chosen to statistically analyse the data according to the classification criteria. There was no statistically significant difference in the rate of postoperative wound infections among ostomate and nonostomate (odds ratio [OR], 1.79; 95% confidence interval [CI], 0.66, 4.84; p = 0.25). In 5 trials, the incidence of anastomotic leak was increased after surgery in nonostomate patients (OR, 0.26; 95% CI, 0.12, 0.57; p = 0.0009). Two studies reported no significant difference in the length of operation time when nonstomal compared to stomal operations in patients with rectal cancer (mean difference, 0.87; 95% CI, -2.99, 4.74; p = 0.66). No significant difference was found in the rate of wound infection and operation time after operation among the two groups, but the incidence of anastomosis leak increased after operation. Protective ileostomy after laparoscopic rectal cancer was effective in reducing the risk of anastomotic leakage in patients, and we found no additional risk of infection. We cautiously conclude that protective ileostomy is active and necessary for patients with a high risk of anastomotic leakage after surgery, which needs to be further confirmed by high-quality studies with larger samples.

NEAT1 promotes the malignant development of bladder cancer by regulating the miR-101/VEGF-C pathway in vitro and in vivo.

BACKGROUND: NEAT1 has been shown to play an oncogenic role in many kinds of cancers. However, detailed roles of NEAT1 in bladder cancer are largely unknown. METHODS: In the present study, the expression of NEAT1, miR-101 and VEGF-C was detected in human bladder cancer samples. The relationship between NEAT1 and the prognosis of patients with bladder cancer was analysed. In vitro experiments explored the effects of NEAT1 on biological behaviours of bladder cancer T24 and 5637 cells. Bioinformatics prediction and luciferase assays were used to assay the regulatory mechanism of action of NEAT1 and miR-101. Loss and gain of the expression of miR-101 and VEGF-C were used to explore the effects of the NEAT1/miR-101/VEGF-C pathway on T24 and 5637 cells. The effect of NEAT1 on the growth of bladder cancer in vivo was explored using an orthotopic tumourigenesis model. RESULTS: NEAT1 and VEGF-C were significantly upregulated in bladder cancer samples, and miR-101 was significantly downregulated. NEAT1 upregulation was associated with poorer recurrence-free survival of patients with bladder cancer. Overexpression of NEAT1 promoted the proliferation, migration and invasion of bladder cancer cells. The results of the luciferase assay indicated that miR-101 was a target of NEAT1. The promoting effects of NEAT1 on bladder cancer cells were reversed by miR-101 upregulation, and inhibition of miR-101 enhanced the effects of NEAT1. Overexpression of VEGF-C had a clear synergistic effect with the action of NEAT1. Overexpression of NEAT1 increased tumour growth and induced the development of liver metastasis. CONCLUSIONS: In conclusion, our data indicated that NEAT1 was expressed at high levels in bladder cancer patients and correlated with unfavourable prognosis. NEAT1 promoted malignant development of bladder cancer in vitro and in vivo by regulating the miR-101/VEGF-C pathway.

Alterations of brain structural and functional connectivity networks topology and decoupling in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease.

OBJECTIVE: To investigate the alteration in structural and functional connectivity networks (SCN and FCN) as well as their coupling in pediatric myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and determine if these properties could serve as potential biomarkers for the disease. MATERIALS AND METHODS: In total of 32 children with MOGAD and 30 age- and sex-matched healthy controls (HC) were employed to construct the SCN and FCN, respectively. The graph-theoretical analyses of the global properties, node properties of the 90 brain nodes, and the structural-functional connectivity (SC-FC) coupling of the two networks were performed. The graph-theoretical properties that exhibited significant differences were analyzed using partial correlation analysis in conjunction with the clinical scales, including the expanded disability status scale (EDSS), modified Rankin scale (mRS), and pediatric cerebral performance category (PCPC) of the MOGAD group. Subsequently, a machine learning model was developed to discriminate between MOGAD and the HC group, aiming to explore the potential of these properties as biomarkers. RESULTS: The SCN of the MOGAD group exhibited aberrant global properties, including an increased characteristic path length (Lp) and a decreased global efficiency (Eg), along with reduced nodal properties such as degree centrality (Dc), nodal efficiency (Ne), and local efficiency in multiple nodes. The FCN of the MOGAD group only exhibited decreased Dc, Ne, and betweenness centrality in two nodes of nodal properties. Besides, MOGAD showed a significant decrease in SC-FC coupling compared to the HC group. The analysis of partial correlation revealed significant correlations between several properties and the scales of EDSS and mRS in the MOGAD group. The machine learning method was used to extract six features and establish the model, achieving a classification accuracy of 82.3% for MOGAD. CONCLUSIONS: Pediatric MOGAD showed a more pronounced impairment in the SCN along with decoupling of SC-FC. Both partial correlation analysis and discriminant modeling suggest that alterations in brain network properties have the potential as biomarkers for assessing brain damage in MOGAD.

Predicting Long-Term Outcome of Prolonged Disorder of Consciousness in Children Through Machine Learning Based on Conventional Structural Magnetic Resonance Imaging.

BACKGROUND: The prognosis of prolonged disorders of consciousness (pDoC) in children has consistently posed a formidable challenge in clinical decision-making. OBJECTIVE: This study aimed to develop a machine learning (ML) model based on conventional structural magnetic resonance imaging (csMRI) to predict outcomes in children with pDoC. METHODS: A total of 196 children with pDoC were included in this study. Based on the consciousness states 1 year after brain injury, the children were categorized into either the favorable prognosis group or the poor prognosis group. They were then randomly assigned to the training set (n = 138) or the test set (n = 58). Semi-quantitative visual assessments of brain csMRI were conducted and Least Absolute Shrinkage and Selection Operator regression was used to identify significant features predicting outcomes. Based on the selected features, support vector machine (SVM), random forests (RF), and logistic regression (LR) were used to develop csMRI, clinical, and csMRI-clinical-merge models, respectively. Finally, the performances of all models were evaluated. RESULTS: Seven csMRI features and 4 clinical features were identified as important predictors of consciousness recovery. All models achieved satisfactory prognostic performances (all areas under the curve [AUCs] >0.70). Notably, the csMRI model developed using the SVM exhibited the best performance, with an AUC, accuracy, sensitivity, and specificity of 0.851, 0.845, 0.844, and 0.846, respectively. CONCLUSIONS: A csMRI-based prediction model for the prognosis of children with pDoC was developed, showing potential to predict recovery of consciousness 1 year after brain injury and is worth popularizing in clinical practice.

Current progression in application of extracellular vesicles in central nervous system diseases.

Early diagnosis and pharmacological treatment of central nervous system (CNS) diseases has been a long-standing challenge for clinical research due to the presence of the blood-brain barrier. Specific proteins and RNAs in brain-derived extracellular vesicles (EVs) usually reflect the corresponding state of brain disease, and therefore, EVs can be used as diagnostic biomarkers for CNS diseases. In addition, EVs can be engineered and fused to target cells for delivery of cargo, demonstrating the great potential of EVs as a nanocarrier platform. We review the progress of EVs as markers and drug carriers in the diagnosis and treatment of neurological diseases. The main areas include visual imaging, biomarker diagnosis and drug loading therapy for different types of CNS diseases. It is hoped that increased knowledge of EVs will facilitate their clinical translation in CNS diseases.

Progress in Brain Magnetic Resonance Imaging of Individuals with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS), a rare epigenetic disease mapping the imprinted chromosomal domain of 15q11.2-q13.3, manifests a regular neurodevelopmental trajectory in different phases. The current multimodal magnetic resonance imaging (MRI) approach for PWS focues on morphological MRI (mMRI), diffusion MRI (dMRI) and functional MRI (fMRI) to uncover brain alterations. This technique offers another perspective to understand potential neurodevelopmental and neuropathological processes of PWS, in addition to specific molecular gene expression patterns, various clinical manifestations and metabolic phenotypes. Multimodal MRI studies of PWS patients demonstrated common brain changes in the volume of gray matter, the integrity of the fiber tracts and the activation and connectivity of some networks. These findings mainly showed that brain alterations in the frontal reward circuit and limbic system were related to molecular genetics and clinical manifestations (e.g., overwhelming eating, obsessive compulsive behaviors and skin picking). Further exploration using a large sample size and advanced MRI technologies, combined with artificial intelligence algorithms, will be the main research direction to study the structural and functional changes and potential pathogenesis of PWS.

m6A-mediated upregulation of lncRNA RMRP boosts the progression of bladder cancer via epigenetically suppressing SCARA5.

Aim: This study aimed to elucidate the relationship between SCARA5 and RMRP in bladder cancer and their underlying mechanism. Methods: Biological functions were evaluated using cell-counting kit 8 assay, 5-ethynyl-2'-deoxyuridine incorporation, wound healing and Transwell assays. RNA immunoprecipitation, RNA pull-down and chromatin immunoprecipitation were employed. A xenograft tumor model in nude mice was also conducted. Results & conclusion: RMRP and SCARA5 exhibited an inverse correlation. Downregulation of RMRP significantly suppressed bladder cancer cell proliferation, migration and invasion, which was reversed by SCARA5 overexpression. RMRP recruited DNA methyltransferases to the promoter region of SCARA5, thereby triggering the methylation of the SCARA5 promoter to epigenetically suppress its expression. Our findings elucidate the machinery by which RMRP, stabilized by METTL3, exerts a promoter role in bladder cancer tumorigenesis by triggering SCARA5 methylation.

The normal reference values and estimation formulae of renal structural parameters in Chinese children based on large-sample CT data.

Purpose: Our aim was to investigate the normal reference value and to establish an estimation formulae for renal structural parameters (RSPs) based on large-sample CT data of Chinese children, which can provide a data reference for the clinical assessment of kidney development and diseases in Chinese children. Materials and Methods: A total of 438 children aged 0-17 years with normal renal CT images and basic indices were continuously collected. The bilateral RSP, including renal length (RL), renal width (RW), renal thickness (RT), renal volume (RV), renal cortical thickness (RCT), renal artery diameter (RAD) and renal CT value, were measured. Kendall's rank correlation was used to analyze the correlation between RSP and sex. Pearson's correlation was used to analyze the correlation between RSP and age, height and weight. Differences in the RSP of bilateral kidneys were analyzed via a paired samples t-test. Multiple linear regression was used to analyze the multivariate relationships between RSP and basic indices and establish the estimation formula of RSP. Results: The RSP of normal kidneys showed a dynamic increasing trend with age, except for the CT values. The reference value ranges (95% confidence interval) of normal RSP for each age group were determined. Pearson correlation analysis demonstrated strong correlations between RSP (RL, RW, RT, RV, RCT and, RAD) and basic indices (age, height and, weight), with height exhibiting the greatest correlation coefficient, followed by age or weight. Kendall's analysis showed that none of the RSPs were correlated with sex. The RL, RW, RV and RAD of the left kidney were larger than those of the right kidney, and the RT and RCT of the right kidney exhibited opposite results. Multiple linear regression analysis demonstrated a significant linear relationship between the RSP (RL, RW, RT, RV and, RCT) and the variables of the basic indices. The estimation formulae for calculating the RSP were established. Conclusion: This is the first Chinese study to report of the trends, normal reference values and estimation formulae of normal RSP based on large-sample CT data. These results can provide data references for assessing adequate kidney growth or disease damage in Chinese children.

Rapid Fabrication of Flexible Cu@Ag Flake/SAE Composites with Exceptional EMIS and Joule Heating Performance.

High electromagnetic interference shielding (EMIS) effectiveness and good thermal management properties are both required to meet the rapid development of integrated electronic components. However, it remains challenging to obtain environmentally friendly and flexible films with high EMIS and thermal management performance in an efficient and scalable way. In this paper, an environmentally friendly strategy is proposed to synthesize multifunctional waterborne Cu@Ag flake conductive films using water as the solvent and silicone-acrylic emulsion (SAE) as a matrix. The obtained films show high electrical conductivity and exceptional EMI SE and electrothermal conversion properties. The EMI SE in the X-band is higher than 76.31 dB at a thickness of 60 µm owing to the ultrahigh electrical conductivity of 1073.61 S cm-1. The film warms up quickly to 102.1 °C within 10 s under a low voltage of 2.0 V. In addition, the shielding coating is sufficiently flexible to retain a conductivity of 93.4% after 2000 bending-release cycles with a bending radius of 3 mm. This work presents an alternative strategy to produce high EMIS effectiveness and Joule heating films for highly integrated and flexible electronic components in a green, scalable, and highly efficient way.

Classification of Myelin Oligodendrocyte Glycoprotein Antibody-Related Disease and Its Mimicking Acute Demyelinating Syndromes in Children Using MRI-Based Radiomics: From Lesion to Subject.

RATIONALE AND OBJECTIVES: To develop MRI-based radiomics models from the lesion level to the subject level and assess their value for differentiating myelin oligodendrocyte glycoprotein antibody-related disease (MOGAD) from non-MOGAD acute demyelinating syndromes in pediatrics. MATERIALS AND METHODS: 66 MOGAD and 66 non-MOGAD children were assigned to the training set (36/35), internal test set (14/16), and external test set (16/15), respectively. At the lesion level, five single-sequence models were developed alongside a fusion model (combining these five sequences). The radiomics features of each lesion were quantified as the lesion-level radscore (LRS) using the best-performing model. Subsequently, a lesion-typing function was employed to classify lesions into two types (MOGAD-like or non-MOGAD-like), and the average LRS of the predominant type lesions in each subject was considered as the subject-level radscore (SRS). Based on SRS, a subject-level model was established and compared to both clinical models and radiologists' assessments. RESULTS: At the lesion level, the fusion model outperformed the five single-sequence models in distinguishing MOGAD and non-MOGAD lesions (0.867 and 0.810 of area under the curve [AUC] in internal and external testing, respectively). At the subject level, the SRS model showed superior performance (0.844 and 0.846 of AUC in internal and external testing, respectively) compared to clinical models and radiologists' assessments for distinguishing MOGAD and non-MOGAD. CONCLUSION: MRI-based radiomics models have potential clinical value for identifying MOGAD from non-MOGAD. The fusion model and SRS model can distinguish between MOGAD and non-MOGAD at the lesion level and subject level, respectively, providing a differential diagnosis method for these two diseases.

BMSC-derived exosomal lncRNA PTENP1 suppresses the malignant phenotypes of bladder cancer by upregulating SCARA5 expression.

LncRNAs can be transported to tumor cells where they exert regulatory effects by bone marrow mesenchymal stem cells (BMSC)-derived exosomes. Here, we aimed to investigate the functional mechanism of BMSC-derived exosomal lncRNA PTENP1 in the progression of bladder cancer (BC). Methods of BMSC were identified by detecting surface markers through flow cytometry. Exosomes from BMSC were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blot analysis of exosome markers. Cellular internalization of BMSC-derived exosomes (BMSC-Exo) into BC cells was detected by confocal microscopy. CCK-8, colony formation, flow cytometry, wound healing, and transwell assays were adopted to estimate cell proliferation, apoptosis, migration, and invasion abilities, respectively. Interplay between miR-17 and lncRNA PTENP1 or SCARA5 was verified by dual-luciferase reporter, RNA pull down, and/or RNA immunoprecipitation (RIP) assays. Tumor xenograft assay was conducted in nude mice to study the role of exosomal lncRNA PTENP1 in BC progression in vivo. We showed exosomal lncRNA PTENP1 can be delivered into and suppress the malignant phenotypes of BC cells. LncRNA PTENP1 was identified as a sponge of miR-17, and SCARA5 was identified as a target gene of miR-17. The exosomes derived from PTENP1-overexpressing BMSC (BMSCOE-PTENP1-Exo) abolished the promotive effects of miR-17 overexpression or SCARA5 knockdown on the malignant phenotypes of BC cells. Moreover, exosomal lncRNA PTENP1 was demonstrated to inhibit BC tumor growth in nude mice by miR-17/SCARA5 axis. In conclusion, BMSC-derived exosomal PTENP1 suppressed the BC progression by upregulating the expression of SCARA5 via sponging miR-17, offering a potential novel therapeutic target for BC therapy.

WITHDRAWN: SCARA5 regulated by MEG3/miR-141 axis attenuates proliferation, migration and invasion of bladder cancer.

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USP11 facilitates colorectal cancer proliferation and metastasis by regulating IGF2BP3 stability.

The abnormal expression of ubiquitin-specific protease 11 (USP11) is thought to be related to tumor development and progression; however, few studies have reported the biological function and clinical importance of USP11 in colorectal cancer (CRC). Therefore, it is necessary to further explore the role of USP11 in CRC. Immunohistochemical staining was used to explore the association between prognosis and USP11 expression in CRC. Cholecystokinin octapeptide (CCK-8), colony formation, transwell, and animal assays were used to study the abilities of proliferation, migration, and invasion in CRC cells. Co-immunoprecipitation assays, Western blotting, ubiquitination assays, and rescue experiments were performed to elucidate the interaction between USP11 and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3). We verified that USP11 was overexpressed in CRC tissues and was associated with the depth of tumor invasion and metastasis. USP11 knockdown or overexpression could weaken or reinforce the abilities of proliferation, migration, and invasion in CRC cells in vivo or in vitro. IGF2BP3 was protected by USP11 from degradation via deubiquitination. The rescue experiments revealed that IGF2BP3 overexpression could effectively reverse the decrease in cell proliferation, migration, and invasion caused by USP11 knockdown. Therefore, USP11 might be involved in CRC tumorigenesis and development through a USP11-IGF2BP3 axis pathway, and USP11 overexpression might be a novel indicator for poor prognosis and a potential therapeutic target in CRC patients.

[Expression and significance of Clara cell secretory protein in injury lungs of Kunming mice after n-hexane long-term inhalation].

OBJECTIVE: To observe the expression of Clara cell secretory protein(CCSP) in the Kunming mouse model of n-hexane long-term inhalation, and to discuss the functions of Clara cell in injury lung induced by n-hexane. METHODS: 24 healthy mice were randomly divided into 4 groups: one control group and three n-hexane groups (4 w, 8 w and 12 w), 6 each group. Primary concentration of n-hexane was 17.6 g/m3, 8 hours per day, 6 d per week. After inhalation, n-hexane concentration of blood from celiac artery was detected. The lungs were embedded with paraffin and HE staining in the routine. The ratio of Clara cells with CCSP reaction in bronchiole and the number of macrophage cells with lysozyme reaction were determined by immuno-histochemistry. RESULTS: In the poisoning groups, the average n-hexane concentration of blood was significantly higher than that of the control group (P < 0.01). There were apparent pathologic damages in lungs of the poisoning mice. In poisoning 4 w, 8 w and 12 w groups, the ratio of Clara cells was significantly decreased [(73.33 +/- 4.21)%, (60.98 +/- 4.94)%, (34.04 +/- 2.33)% in terminal bronchiole, and (75.44 +/- 7.91)%, (58.54 +/- 4.86)%, (33.35 +/- 2.67)% in respiratory bronchiole] as compared with the control mice [(80.26 +/- 6.43)% and (81.74 +/- 7.75)%, P < 0.05 or P < 0.01], meanwhile the numbers of macrophage cells were gradually increased [(21.39 +/- 7.41), (28.54 +/- 10.73), (48.97 +/- 19.55) per microscopic field at 200x] in poisoning mice than those in control mice [(7.84 +/- 3.12) per microscopic field at 200x, P < 0.05 or P < 0.01]. CONCLUSION: In injury lungs after n-hexane inhalation, Clara cells are the target cells of n-hexane toxicity effect. Clara cells play an extensive protective role in lung inflammation.

miR­204­5p promotes apoptosis and inhibits migration of gastric cancer cells by targeting HER­2.

Gastric cancer is one of the most common types of cancer worldwide, with a high incidence and mortality rate. MicroRNAs (miRs) play an important role in tumorigenesis, cell proliferation, migration, apoptosis and metastasis of cancer. The present study aimed to investigate the role and potential mechanism of miR­204­5p in gastric cancer. The mRNA expression levels of miR­204­5p in gastric cancer were determined by reverse transcription­quantitative PCR. Cell proliferation was determined using Cell Counting Kit­8 and colony formation assays. Flow cytometry analysis was performed to detect the cell apoptosis rate. Wound healing and Transwell assays were carried out to determine the cell migration and invasion rates, respectively. A putative binding site of miR­204­5p in the 3' untranslated region of human epidermal growth factor receptor 2 (HER­2) was predicted using a bioinformatics algorithm and confirmed using a dual­luciferase reporter assay. miR­204­5p levels were downregulated in gastric cancer cells. Overexpression of miR­204­5p significantly inhibited cell proliferation and decreased cell colony formation. Additionally, miR­204­5p decreased the migration and invasion rates of gastric cancer cells. Furthermore, an increased apoptotic rate was detected following overexpression of miR­204­5p, along with increased expression levels of Bax and decreased expression levels of Bcl­2. HER­2 was a direct target of miR­204­5p, and inhibition of HER­2 acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis, which was reversed by the inhibition of miR­204­5p expression. These results suggested that miR­204­5p could exert its anti­tumor function by inhibiting cell proliferation, migration and invasion, and promoting cell apoptosis via regulation of HER­2, which may be a potential therapeutic target for gastric cancer.

miR­21 inhibits autophagy and promotes malignant development in the bladder cancer T24 cell line.

MicroRNA­21 (miR­21) is reported to exhibit cancer­promoting activity in various types of cancer. It has been previously demonstrated that miR­21 is overexpressed in bladder tumor tissue compared with normal mucosa. However, the functional mechanism of miR­21 in bladder cancer remains largely unknown. Thus, the current study aimed to determine the roles of miR­21 in autophagy and the malignant development of bladder cancer in T24 cells. Upregulation or downregulation of miR­21 was achieved following the transfection of miR­21 mimic or miR­21 inhibitor. An MTT assay was additionally performed to measure cell growth. Wound healing and transwell invasion assays were used to detect cell migration and invasion. The apoptotic potential and cell cycle were examined via flow cytometry and reverse transcription­quantitative PCR was performed to evaluate the expression of phosphatase and tensin homolog (PTEN), beclin 1, microtubule­associated protein l light chain 3B (LC3­II), cyclin D1, caspase­3, E­cadherin, matrix metallopeptidase­9 (MMP­9) and vimentin. The results revealed that the proliferation, migration and invasion of T24 cells was greatly increased in the miR­21 mimic group, while apoptosis was greatly inhibited. Additionally, T24 cells treated with miR­21 mimic exhibited G1­phase arrest. In the miR­21 mimic group, the expression of PTEN, beclin 1, LC3­II, caspase­3 and E­cadherin were decreased, while the expression of cyclin D1, MMP­9 and vimentin were increased. Opposite effects were observed in the miR­21 inhibitor group. The data of the current study may indicate that miR­21 overexpression inhibited autophagy and promoted the proliferation, migration, invasion and epithelial to mesenchymal transition of bladder cancer T24 cells. The results may further elucidate the molecular mechanism of miR­21 in the development of bladder cancer.