Identification of diagnostic signature and immune microenvironment subtypes of venous thromboembolism.

The close link between immune and pathogenesis of venous thromboembolism (VTE) has been recognized, but not fully elucidated. The current study was designed to identify immune microenvironment related signature and subtypes using explainable machine learning in VTE. We first observed an alteration of immune microenvironment in VTE patients and identified eight key immune cells involved in VTE. Then PTPN6, ITGB2, CR2, FPR2, MMP9 and ISG15 were determined as key immune microenvironment-related genes, which could divide VTE patients into two subtypes with different immune and metabolic characteristics. Also, we found that prunetin and torin-2 may be most promising to treat VTE patients in Cluster 1 and 2, respectively. By comparing six machine learning models in both training and external validation sets, XGboost was identified as the best one to predict the risk of VTE, followed by the interpretation of each immune microenvironment-related gene contributing to the model. Moreover, CR2 and FPR2 had high accuracy in distinguishing VTE and control, which may act as diagnostic biomarkers of VTE, and their expressions were validated by qPCR. Collectively, immune microenvironment related PTPN6, ITGB2, CR2, FPR2, MMP9 and ISG15 are key genes involved in the pathogenesis of VTE. The VTE risk prediction model and immune microenvironment subtypes based on those genes might benefit prevention, diagnosis, and the individualized treatment strategy in clinical practice of VTE.

Iron ions-sequestrable and antioxidative carbon dot-based nano-formulation with nitric oxide release for Parkinson's disease treatment.

Nondestructive penetration of the blood-brain barrier (BBB) to specifically prevent iron deposition and the generation of reactive oxygen species (ROS) shows great potential for treating Parkinson's disease (PD). However, effective agents with distinct mechanisms of action remain scarce. Herein, a N-doping carbon dot (CD) emitting red light was prepared, which can sacrifice ROS and produce nitric oxide (NO) owing to its surface N-involved groups conjugated to the sp2-hybrided π-system. Meanwhile, CD can chelate iron ions, thus depressing the catalytic Fe cycle and *OH detaching to inhibit the Fenton reaction. By modifying lactoferrin (Lf) via polyethylene glycol (PEG), the resulting CD-PEG-Lf (CPL) can nondestructively cross the BBB, targeting the dopaminergic neurons via both NO-mediated reversible BBB opening and Lf receptor-mediated transportation. Accordingly, it can serve as an antioxidant, reducing oxidative stress via its unique iron chelation, free radical sacrificing, and synergy with iron reflux prevention originating from Lf. Thus, it can significantly reduce brain inflammation and improve the behavioral performance of PD mice. Additionally, CPL can image the PD via its red fluorescence. Finally, this platform can be metabolized out of the brain through cerebrospinal fluid circulation without causing obvious side effects, promising a robust treatment for PD.

LY86 facilitates ox-LDL-induced lipid accumulation in macrophages by upregulating SREBP2/HMGCR expression.

LY86, also known as MD1, has been implicated in various pathophysiological processes including inflammation, obesity, insulin resistance, and immunoregulation. However, the role of LY86 in cholesterol metabolism remains incompletely understood. Several studies have reported significant up-regulation of LY86 mRNA in atherosclerosis; nevertheless, the regulatory mechanism by which LY86 is involved in this disease remains unclear. In this study, we aimed to investigate whether LY86 affects ox-LDL-induced lipid accumulation in macrophages. Firstly, we confirmed that LY86 is indeed involved in the process of atherosclerosis and found high expression levels of LY86 in human atherosclerotic plaque tissue. Furthermore, our findings suggest that LY86 may mediate intracellular lipid accumulation induced by ox-LDL through the SREBP2/HMGCR pathway. This mechanism could be associated with increased cholesterol synthesis resulting from enhanced endoplasmic reticulum stress response.

A Biodegradable Nanosuspension Locally Used for Inhibiting Postoperative Recurrence and Brain Metastasis of Breast Cancer.

Addressing the urgent need to prevent breast cancer postoperative recurrence and brain metastasis, Fe-metal organic framework (MOF)-coated hollow mesoporous organosilica nanoparticles (HMON) with tumor microenvironment dual-responsive degradability were prepared to encapsulate doxorubicin (DOX), formulating a tissue-adhesive nanosuspension for perioperative topical medication. This nanosuspension can not only retain the sustainably released drug in the postoperative residual tumor sites but also enhance the intracellular oxidative stress of tumors for remarkable tumor ferroptosis. Interestingly, the nanosuspension can act as an immune amplifier, which could not only stimulate DC cells to secrete chemokines for T cell recruitment but also elevate antigen exposure to facilitate the antigen presentation in lymph nodes. Thus, this nanosuspension could significantly activate antitumor immune responses in both in situ tumors and metastatic encephaloma for enhanced immunotherapy. In conjunction with the clinical PD-1 antibody, the locally administered nanosuspension could achieve an advanced therapeutic outcome for inhibiting postoperative recurrence and metastasis.

Relationship between hyperlipidemia and the risk of death in aneurysm: a cohort study on patients of different ages, genders, and aneurysm locations.

Aims: The study aimed to assess the association of hyperlipidemia and the risk of death in the aneurysm population, focusing on age, gender, and aneurysm location differences. Methods: All patients' data on this retrospective cohort study were obtained from the Medical Information Mart for Intensive Care (MIMIC-III) database, and the baseline characteristics and laboratory parameters of all patients were collected. The COX regression model was established to explore the association of hyperlipidemia and the risk of death for patients with aneurysms. More importantly, subgroup analyses based on the age, gender, and aneurysm location differences were performed. Results: A total of 1,645 eligible patients were enrolled in this study. These patients were divided into the survival group (n = 1,098) and the death group (n = 547), with a total mortality rate of approximately 33.25%. The result displayed that hyperlipidemia was associated with a decreased death risk in aneurysm patients. In addition, we also found that hyperlipidemia was associated with a lower death risk of abdominal aortic aneurysm and thoracic aortic arch aneurysm among aneurysm patients aged ≥60 years; hyperlipidemia was only a protective factor for the death risk of male patients diagnosed with abdominal aortic aneurysm. For female patients diagnosed with abdominal aortic aneurysm and thoracic aortic arch aneurysm, hyperlipidemia was associated with a decreased death risk. Conclusion: The relationship of hyperlipidemia, hypercholesterolemia, and the risk of death for patients diagnosed with aneurysms was significantly associated with age, gender, and aneurysm location.

Novel immune cell infiltration-related biomarkers in atherosclerosis diagnosis.

Background: Immune cell infiltration (ICI) has a close relationship with the progression of atherosclerosis (AS). Therefore, the current study was aimed to explore the role of genes related to ICI and to investigate potential mechanisms in AS. Methods: Single-sample gene set enrichment analysis (ssGSEA) was applied to explore immune infiltration in AS and controls. Genes related to immune infitration were mined by weighted gene co-expression network analysis (WGCNA). The function of those genes were analyzed by enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The interactions among those genes were visualized in the protein-protein interaction (PPI) network, followed by identification of hub genes through Cytoscape software. A receiver operating characteristic (ROC) plot was generated to assess the performance of hub genes in AS diagnosis. The expressions of hub genes were measured by reverse transcription quantitative real-time PCR (RT-qPCR) in human leukemia monocyticcell line (THP-1) derived foam cells and macrophages, which mimic AS and control, respectively. Results: We observed that the proportions of 27 immune cells were significantly elevated in AS. Subsequent integrative analyses of differential expression and WGCNA identified 99 immune cell-related differentially expressed genes (DEGs) between AS and control. Those DEGs were associated with tryptophan metabolism and extracellular matrix (ECM)-related functions. Moreover, by constructing the PPI network, we found 11 hub immune cell-related genes in AS. The expression pattern and receiver ROC analyses in two independent datasets showed that calsequestrin 2 (CASQ2), nexilin F-Actin binding protein (NEXN), matrix metallopeptidase 12 (MMP12), C-X-C motif chemokine ligand 10 (CXCL10), phospholamban (PLN), heme oxygenase 1 (HMOX1), ryanodine receptor 2 (RYR2), chitinase 3 like 1 (CHI3L1), matrix metallopeptidase 9 (MMP9), actin alpha cardiac muscle 1 (ACTC1) had good performance in distinguishing AS from control samples. Furthermore, those biomarkers were shown to be correlated with angiogenesis and immune checkpoints. In addition, we found 239 miRNAs and 47 transcription factor s (TFs), which may target those biomarkers and regulate their expressions. Finally, we found that RT-qPCR results were consistent with sequencing results.

Bronchoalveolar lavage fluid polymerase chain reaction for invasive pulmonary aspergillosis among high-risk patients: a diagnostic meta-analysis.

BACKGROUND: Polymerase chain reaction (PCR) assays are perceived to facilitate the diagnosis of fungal infections. However, due to lack of standardization, the value of bronchoalveolar lavage (BAL) fluid PCR in diagnosis of invasive pulmonary aspergillosis (IPA) remains unclear. METHODS: We conducted a systematic meta-analysis to evaluate the accuracy of BAL fluid PCR in IPA diagnosis among high-risk patients. All studies involving patients at risk for IPA were included. The sensitivity, specificity, positive and negative likelihood ratios of BAL fluid PCR were summarized for diagnosis of proven/probable IPA, or proven IPA only. Potential heterogeneity was assessed by subgroup analyses and meta-regression. RESULTS: Forty-one studies involving 5668 patients were analyzed. The summary sensitivity, specificity, positive and negative likelihood ratios of BAL fluid PCR for proven/probable IPA were 0.75 (95% CI = 0.67-0.81), 0.94 (95% CI = 0.90-0.96), 11.8 (95% CI = 7.7-18.1) and 0.27 (95% CI = 0.20-0.36), respectively. Whereas for proven IPA only, sensitivity and specificity were 0.91 (95% CI = 0.68-0.98) and 0.80 (95% CI = 0.74-0.85) in fourteen studies involving 2061 patients. Significant heterogeneity was present due to the underlying disease, antifungal treatment and differences in DNA extraction techniques and choice of PCR assay. Compared to patients with hematological malignancies (HM) and hematopoietic stem cell/solid organ transplantation (HSCT/SOT), sensitivity was higher in the population with disease such as chronic obstructive pulmonary disease, solid tumor, autoimmune disease with prolonged use of corticosteroids, etc. (0.88 vs. 0.68, P < 0.001), which was related to the concurrent use of antifungal prophylaxis among patients with HM and HSCT/SOT. CONCLUSION: BAL fluid PCR is a useful diagnostic tool for IPA in immunocompromised patients and is also effective for diagnosing IPA in patients without HM and HSCT/SOT. Furthermore, standard protocols for DNA extraction and PCR assays should be focused on to improve the diagnostic accuracy. Trial registration PROSPERO, registration number CRD42021239028.

Identification of immune-related biomarkers and construction of regulatory network in patients with atherosclerosis.

BACKGROUND: More and more evidence has established the crucial roles of the innate and adaptive immune systems in driving atherosclerosis-associated chronic inflammation in arterial blood vessels. Thus, the goal of this research was to determine immune-related biomarkers in atherosclerosis. METHODS: In this study, we conducted analysis on the mRNA expression profile of atherosclerosis obtained from Gene Expression Omnibus. Differentially expressed genes (DEGs) between atherosclerosis and control samples and immune-related genes (IRGs) were intersected to obtain differentially expressed immune-related genes (DEIRGs). The protein-protein interaction (PPI) network was created by STRING database and hub genes were identified by the MCODE plug-in. Furthermore, the receiver operating characteristic (ROC) curve was executed to verify the diagnostic value of the hub genes, and microRNA (miRNA)-gene-transcription factor (TF) regulatory networks were used to explain the regulatory mechanism of hub genes in atherosclerosis. Finally, qRT-PCR was performed to identify the mRNA levels of the target genes. RESULTS: A total of 199 overlapping genes were screened out as DEIRGs by intersecting the DEGs and IRGs. Then, 6 hub genes with high diagnostic value (IFIH1, IFIT1, IFIT2, IFIT3, ISG15 and OAS3) were identified via PPI network and ROC curve. Finally, miRNA-gene-TF networks revealed the regulatory mechanism of diagnostic genes.We used the carotid artery of AS patients and normal human carotid artery plaque samples for qRT-PCR verification, and the results showed that the hub gene had the same trend. CONCLUSION: Our study identified IFIH1, IFIT1, IFIT2, IFIT3, ISG15 and OAS3 as immune-related hub genes of atherosclerosis. These genes may serve as potential therapeutic targets for atherosclerosis patients.

Relationship between the neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio and deep venous thrombosis (DVT) following femoral neck fractures in the elderly.

Purpose: This study aimed to investigate whether the neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) was associated with deep venous thrombosis (DVT) following femoral neck fractures in the elderly. Method: This was a retrospective cohort study and used data extracted from the hospitalization electronic medical record and the laboratory biomarker reports. Patients were included if they were aged above 60 years with a definite diagnosis of femoral neck fracture caused by low-energy trauma. Duplex ultrasound scanning was routinely performed to detect the potential DVT. Two independent multivariate logistic regression models were constructed to identify the association of NLR or PLR with the risk of DVT. Results: A total of 708 patients with femoral neck fractures were included, and 112 were found to have DVT, indicating an incidence rate of 15.8%. There were significant differences across five subgroups for NLR or PLR, in terms of age (p = 0.020, 0.006), white blood cell (p < 0.001, =0.006), hemoglobin (p < 0.001, <0.001), and albumin (p < 0.001, <0.001). BMI was tested to be significantly different across subgroups for NLR (p = 0.030) and prevalence of cerebrovascular disease for PLR (p = 0.014). The multivariate analyses demonstrated that not NLR but PLR in Q3 (range, 179-238) was associated with an increased risk of DVT, and the risk for the latter was 1.86 (95%CI, 1.07-3.36). Conclusion: We concluded that a PLR value of 179-238 was associated with a 1.86-fold increased risk of DVT after femoral neck fracture. This study paves the way toward further exploration of inflammatory/immune biomarkers with the risk of DVT in the elderly with trauma.

Efficacy of one-stop endovascular intervention in treatment of left iliac vein compression syndrome complicated with deep venous thrombosis of lower limbs.

OBJECTIVE: To evaluate the clinical effect and safety of one-stop endovascular intervention in treatment of left iliac vein compression syndrome (IVCS) complicated with deep venous thrombosis (DVT) of lower limbs. METHODS: Clinical data of 26 patients with secondary DVT due to IVCS admitted in the Department of Vascular Surgery, Hebei General Hospital from January 2018 to December 2021 were retrospectively analyzed. All patients underwent one-stop endovascular intervention procedure, including ultrasound-guided deep venipuncture, Angiojet catheter aspiration, iliac vein balloon dilation, stent implantation and simultaneous filter retrieval. The operation time and catheter aspiration time were documented; the preoperative and postoperative left lower extremity deep vein venous patency, circumferences of bilateral limbs at 15 cm above the knee and 10 cm below the knee, and the levels of hemoglobin, creatinine, alanine aminotransferase (ALT), aspertate aminotransferase (AST), total bilirubin and indirect bilirubin were measured. The incidence of post-thrombotic syndrome (PTS) and iliac vein stent patency were recorded through follow-up. RESULTS: The one-stop endovascular intervention was successfully performed in 26 patients, with the operation time of (171±35) min and the thrombolysis time of (263±89) s. After treatment, the left lower extremity deep vein venous patency, circumferences of bilateral limbs at 15 cm above the knee and 10 cm below the knee were decreased (all P<0.01); the hemoglobin level were decreased, the creatinine, ALT, AST, total bilirubin and indirect bilirubin levels were increased (all P<0.01). Patients were followed up for 1-12 months. Stent thrombosis occurred in 1 patient 7 months after procedure, and the symptoms were improved after conservative treatment; the stents were unobstructed in all patients, 1 patient had stent mural thrombosis, in whom the stent blood flow was not affected. No PTS was observed during the follow-up. CONCLUSIONS: The one-stop endovascular interventional treatment of IVCS complicated with DVT of left lower limb is safe and effective. Attention should be paid to the changes of liver and kidney function caused by catheter aspiration during the treatment, and corresponding intervention should be given in time to avoid the occurrence of related complications.

hsa_circ_0084811 Regulates Cell Proliferation and Apoptosis in Retinoblastoma through miR-18a-5p/miR-18b-5p/E2F5 Axis.

Background: Retinoblastoma (RB) is the commonest primary intraocular malignancy during childhood. Circular RNAs (circRNAs) act as regulators in RB development, and hsa_circ_E2F5 (circ_0084811 in this study) was found to be highly expressed in RB cells, so we wanted to identify its detailed molecular mechanism. Methods: The expression level of circ_0084811 in RB cells was tested by RT-qPCR and its effects on RB cells were evaluated through functional assays. The regulatory mechanism that circ_0084811 may exert in RB progression was testified through mechanism experiments. Results: High circ_0084811 expression in RB cells facilitated cell proliferation but inhibited cell apoptosis. The enrichment of acetylation of histone 3 lysine 27 (H3K27ac) in circ_0084811 promoter induced circ_0084811 upregulation. Moreover, circ_0084811 regulated E2F transcription factor 5 (E2F5) expression via sponging microRNA-18a-5p (miR-18a-5p) and microRNA-18b-5p (miR-18b-5p). Conclusion: circ_0084811 modulated RB progression via the miR-18a-5p/miR-18b-5p/E2F5 axis.

Extracellular Vesicle-Derived miR-26b-5p is Up-Regulated in the Serum of Patients with Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a severe complication of diabetes; however, the pathogenesis of DR has not been completely clarified, which is mostly dependent on the molecular pathology. This study aimed to investigate key serum-derived miRNAs associated with DR. METHODS: miRNA expression profile arrays of human umbilical vein endothelial cells (HUVECs) treated with glucose were downloaded from the Gene Expression Omnibus (GEO) database (GSE74296). Weighted gene co-expression network analysis (WGCNA) was performed to obtain hub miRNAs, which were verified in HUVECs treated with 40 mM and 5 mM glucose, respectively. Meanwhile, serum samples of patients with DR and healthy controls were collected, and EVs were extracted from the patients' serum by ultracentrifugation. Hub miRNAs associated with endothelial dysfunction were verified in healthy individuals before and after treatment of patients with DR, by qRT-PCR. RESULTS: These miRNAs were categorized into six modules, among which miR-26b-5p had a strong association with other modules. This miRNA was also one of the hyperglycemia-induced miRNAs related to endothelial dysfunction. miR-26b-5p was up-regulated in HUVECs treated with 40 mM glucose and in the serum of patients with DR before and after treatment. Furthermore, miR- 26b-5p was slightly up-regulated in serum-derived EVs but not in serum without EVs in DM patients. CONCLUSION: Our results suggest that EVs derived from miR-26b-5p are up-regulated in the serum of patients with DR.

Preoperative deep venous thrombosis (DVT) after femoral neck fracture in the elderly, the incidence, timing, location and related risk factors.

OBJECTIVE: To investigate the epidemiologic characteristics of deep venous thrombosis (DVT) in elderly patients with femoral neck fracture. METHODS: Retrospective analysis was performed on elderly patients with femoral neck fractures admitted to two institutions from January 2016 to October 2019. Duplex ultrasonography (DUS) was used to detect DVT. Patients' hospitalization medical records were retrieved to collect the data, which were related to demographics, comorbidities, injury and laboratory results on admission. Patients with preoperative DVT were defined as the case group and those without DVT as control group, and compared using the univariate analyses. Multivariate logistic regression analysis was used to identify the independent factors associated with DVT. RESULTS: Totally, 980 patients met the predefined criteria and were included. Sixty-seven patients were diagnosed to have preoperative DVT, with incidence of 6.8% for overall, 1.7% for proximal and 5.1% for distal DVT. The mean time from injury to diagnosis of DVT was 6.0 ± 4.7 days (median, 5.0). Most (76.1%) patients with DVT had thrombi solely in the injured extremity, in contrast with 14.9% (10/67) in the uninjured and 9.0% (6/67) in both injured and uninjured extremity. Multivariate analysis showed chronic renal insufficiency (OR, 3.37; 95%CI, 1.57 to 7.28), current smoking status (OR, 2.42; 95%CI, 1.23 to 5.63), time from injury to DUS (OR, 1.26; 95%CI, 1.07 to 1.61) and PLT > 220*109/L (OR, 1.94; 95%CI, 1.31 to 3.77) were independent factors for DVT. CONCLUSION: Preoperative DVT is not very prevalent following elderly femoral neck fractures, but with a certain proportion in the uninjured extremity, necessitating the more attention. These identified risk factors aid in patient counseling, individualized risk assessment and risk stratification, and should be kept in mind.

Discovery of potential asthma targets based on the clinical efficacy of Traditional Chinese Medicine formulas.

ETHNOPHARMACOLOGICAL RELEVANCE: Standard therapy for asthma, a highly heterogeneous disease, is primarily based on bronchodilators and immunosuppressive drugs, which confer short-term symptomatic relief but not a cure. It is difficult to discover novel bronchodilators, although potential new targets are emerging. Traditional Chinese Medicine (TCM) formulas have been used to treat asthma for more than 2000 years, forming the basis for representative asthma treatments. AIM OF THE STUDY: Based on the efficacy of TCM formulas, anti-asthmatic herbal compounds bind proteins are potential targets for asthma therapy. This analysis will provide new drug targets and discovery strategies for asthma therapy. MATERIALS AND METHODS: A list of candidate herbs for asthma was selected from the classical formulas (CFs) of TCM for the treatment of wheezing or dyspnea recorded in Treatise on Cold Damage and Miscellaneous Diseases (TCDMD) and from modern herbal formulas identified in the SAPHRON TCM Database using the keywords "wheezing" or "dyspnea". Compounds in the selected herbs and compounds that directly bind target proteins were acquired by searching the Herbal Ingredients' Targets Database (HITD), TCM Data Bank (TCMDB) and TCM Integrated Database (TCMID). Therapeutic targets of conventional medicine (CM) for asthma were collected by searching Therapeutic Target Database (TTD), DrugBank and PubMed as supplements. Finally, the enriched gene ontology (GO) terms of the targets were obtained using the Database for Annotation Visualization and Integrated Discovery (DAVID) and protein-protein interactions (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The effects of two selected TCM compounds, kaempferol and ginkgolide A, on cellular resistance in human airway smooth muscle cells (ASMCs) and pulmonary resistance in a mouse model were investigated. RESULTS: The list of 32 candidate herbs for asthma was selected from 10 CFs for the treatment of wheezing or dyspnea recorded in TCDMD and 1037 modern herbal formulas obtained from the SAPHRON TCM Database. A total of 130 compounds from the 32 selected herbs and 68 herbal compounds directly bind target proteins were acquired from HITD and TCMDB. Eighty-eight therapeutic targets of CM for asthma were collected by searching TTD and PubMed as supplements. DAVID and STRING analyses showed targets of TCM formulas are primarily related to cytochrome P450 (CYP) family, transient receptor potential (TRP) channels, matrix metalloproteinases (MMPs) and ribosomal protein. Both TCM formulas and CM act on the same types of targets or signaling pathways, such as G protein-coupled receptors (GPCRs), steroid hormone receptors (SHRs), and JAK-STAT signaling pathway. The proteins directly targeted by herbal compounds, TRPM8, TRPA1, TRPV3, CYP1B1, CYP2B6, CYP1A2, CYP3A4, CYP1A1, PPARA, PPARD, NR1I2, MMP1, MMP2, ESR1, ESR2, RPLP0, RPLP1 and RPLP2, are potential targets for asthma therapy. In vitro results showed kaempferol (1 × 10-2 mM) and ginkgolide A (1 × 10-5 mM) significantly increased the cell index (P < 0.05 vs. histamine, n = 3) and therefore relaxed human ASMCs. In vivo results showed kaempferol (145 µg/kg) and ginkgolide A (205 µg/kg) significantly reduced pulmonary resistance (P < 0.05 vs. methacholine, n = 6). CONCLUSION: Potential target discovery for asthma treatment based on the clinical effectiveness of TCM is a feasible strategy.

miR-125a-5p inhibits colorectal cancer cell epithelial-mesenchymal transition, invasion and migration by targeting TAZ.

Background: miR-125a-5p regulated biological processes in various types of cancer, including colorectal cancer (CRC). TAZ, a vital transcriptional coactivators of the Hippo pathway, was found to be overexpressed in various cancers. Objectives: This study aims to study the effect of miR-125a-5p on the progression of CRC by regulating TAZ expression. Methods: In this study, miR-125a-5p and TAZ expression in CRC tissue and cell lines were detected by real-time polymerase chain reaction (RT-PCR). Luciferase reporter assay was applied to detect whether TAZ was a target of miR-125a-5p. Cell migration and invasion were detected in vitro by wound-healing assay and cell invasion assay. Western blot was used to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins. Findings: The results revealed downregulation of miR-125a-5p, as well as upregulation of TAZ in CRC tissue and cell lines. TAZ was identified as a direct target of miR-125a-5p, and its expression was negatively regulated by miR-125a-5p in CRC cell lines. The functional studies revealed that overexpression of miR-125a-5p inhibited the migration, invasion and EMT of CRC cells, while upregulation of TAZ reversed the inhibitory effect caused by miR-125a-5p. Conclusion: Our data suggest that miR-125a-5p inhibits CRC cell migration, invasion and EMT by targeting TAZ. These results suggest that miR-125a-5p serves as a potential therapeutic biomarker for CRC patients.

AQP5 silencing suppresses p38 MAPK signaling and improves drug resistance in colon cancer cells.

It is known that aquaporin 5 (AQP5) may represent a novel therapeutic target for treating colon cancer (CC), but whether AQP5 plays a role in the regulation of multidrug resistance (MDR) of colon cancer still remains unclear. In the present study, AQP5 and P-glycoprotein (P-gp), glutathione S-transferase-π (GST-π), topoisomerase II (TOPO II), and thymidylate synthase (TS) were checked in CC and adjacent cancer tissues; AQP5-siRNA was applied to silencing AQP5 in CC cell line HT-29, 5-fluorouracil (5-FU), and cisplatin (DDP) added on cells, and sulforhodamine B (SRB) was used; fluorescence real-time quantitative RT-PCR and Western blot were employed to detect changes in multidrug resistance factor and expression mitogen-activated protein kinase (MAPK) signaling pathway in HT-29. The results showed that AQP5 is significantly induced in cancer tissues than that in adjacent cancer tissues. The expression of AQP5 is positively correlated with drug resistance factors, as demonstrated by the increased expressions of P-gp, GST-π, and TOPO II in CC tissues compared to that in adjacent cancer tissues. Conversely, knockdown of AQP5 in HT-29 human colon cancer cells increased inhibition rates of cancer chemotherapeutic drugs such as 5-FU and DDP. The improved efficacies of chemotherapeutic drugs are associated with the decreased expression of P-gp, GST-π, and TOPO II. In addition, phosphorylation of p38 MAPK was increased by knockdown of AQP5 in HT-29 cells while phosphorylation and expression of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and Protein kinase B (AKT) were not affected. P38 MAPK inhibitor increased the drug sensitivity of HT-29 cells in a similar way as AQP5-siRNAs do. So these results indicate that AQP5 is associated with drug resistance of colon cancer, and that the AQP5-P38 MAPK pathway may represent a potential drug target to improve drug resistance of colon cancer cells.

[Response of forest bird communities to forest gap in winter in southwestern China].

Although forest gap ecology is an important field of study, research remains limited. By plot setting and point counted observation, the response of birds to forest gaps in winter as well as bird distribution patterns in forest gaps and intact canopies were studied in a north tropical monsoon forest of southwestern China from November 2011 to February 2012 in the Fangcheng Golden Camellia National Nature Reserve, Guangxi. The regression equation of bird species diversity to habitat factor was Y1=0.611+0.002 X13+0.043 X2+0.002 X5-0.003 X8+0.006 X10+0.008 X1 and the regression equation of bird species dominance index to habitat factor was Y3=0.533+0.001 X13+0.019 X2+0.002 X3-0.017 X4+0.002 X1. There were 45 bird species (2 orders and 13 families) recorded in the forest gap, accounting for 84.9% of all birds (n=45), with an average of 9.6 species (range: 2-22). Thirty-nine bird species (5 orders and 14 families) were recorded in non-gap areas, accounting for 73.6% of all birds (n=39), with an average of 5.3 species (range: 1-12). These results suggested that gap size, arbor average height (10 m from gap margin), arbor quantity (10 m from gap margin), shrub quantity (10 m from gap margin), herbal average coverage (1 m from gap margin) and bare land ratio were the key forest gap factors that influenced bird diversities. On the whole, bird diversity in the forest gap was greater than in the intact canopy. Spatial distributions in the forest gaps were also observed in the bird community. Most birds foraged in the "middle" and "canopy" layers in the vertical stratification. In addition, "nearly from" and "close from" contained more birds in relation to horizontal stratification. Feeding niche differentiation was suggested as the main reason for these distribution patterns.