PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway.

BACKGROUND: This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. METHODS: By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. RESULTS: The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P < 0.01). Smooth muscle cells treated with PGE2 displayed increased cAMP and phosphorylated PKA. CONCLUSIONS: PGE2 binding to EP2 induces ureteral relaxation through the cAMP-PKA pathway. This will provide a new theoretical basis for the development of new therapeutic approaches for the use of PGE2 in the treatment of ureteral stones.

Csn-miR156d-CsSPL1 regulates flowering and anthocyanin metabolism.

MiR156 play important roles in regulation of plant growth and development, secondary metabolite synthesis, and other biological processes by targeting the SQUAMOSA promoter binding protein-like (SPL) family. Our previous sequencing data analysis suggested that Csn-miR156d may regulate flowering and anthocyanin accumulation by cleavage and degradation of the expression of the SPL in tea plant, but it remains to be elucidated. In this study, 5'RLM-RACE experiment, tobacco transient transformation, qRT-PCR, and antisense oligonucleotide (asODN) were used to verify that CsSPL1 is the target gene of Csn-miR156d. Stable transformation of Arabidopsis revealed that Csn-miR156d could delay flowering by negatively regulating the transcript levels of FT, AP1, FUL, and SOC1, while overexpression of CsSPL1 showed an opposite effect. Additionally, overexpression of Csn-miR156d in Arabidopsis could enhance the transcription of the anthocyanin biosynthesis-related structural genes DFR, ANS, F3H, UGT78D2, and LDOX, as well as regulatory genes PAP1, MYB113, GL3, MYB11, and MYB12, leading to anthocyanin accumulation. Moreover, asODN experiment revealed that Csn-miR156d could increase the anthocyanin content in tea plant. These results suggest that Csn-miR156d regulates flowering and anthocyanin accumulation in tea plant by suppressing the expression of CsSPL1. Our study provides new insights into the development and anthocyanin accumulation in tea plant and lays a theoretical foundation for further research on the molecular mechanism of miRNAs in regulating tea plant growth and secondary metabolism.

Efficacy and Safety of Endoscopic Surgery Versus Craniotomy for Hypertensive Putamen Hemorrhage.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of neuroendoscopy for treating hypertensive putamen hemorrhage (HPH), compared with traditional craniotomy. METHODS: We retrospectively analyzed 81 consecutive patients with HPH treated with neuroendoscopy (n=36) or craniotomy (n=45) in the Department of Neurosurgery at the Anhui Provincial Hospital Affiliated to Anhui Medical University between January 2015 and December 2017. We compared the clinical and radiographic outcomes, excluded 14 patients who did not meet the inclusion criteria. Patient characteristics in emergency room were recorded. In addition, hospitalization days, total cost during hospitalization, operative time, blood loss, evacuation rate, rebreeding, intracranial infection, pulmonary infection, epilepsy, hemorrhage of digestive tract, venous thrombus, hypoproteinemia, aphasia, oculomotor paralysis, mortality, Modified Rankin Scale score 6 months after surgery, and Glasgow Outcome Scale score 6 months after surgery were compared between the 2 groups. RESULTS: Comparative analysis of preoperative patient data revealed no notable disparities. Neuroendoscopic surgery afford distinct benefits including reduced operative time, minimal patient blood loss, and enhanced efficacy in hematoma evacuation. However, the incidence of postoperative complications such as rebleeding, intracranial infections, pulmonary infections, postoperative epilepsy, hemorrhage of digestive tract, venous thrombus, hypoproteinemia, aphasia, and oculomotor paralysis did not significantly differ. In contrast, endoscopic techniques, relative to conventional craniotomy for hematoma evacuation, are characterized by less invasive incisions, a marked decrease in the duration of hospitalization, and a substantial reduction in associated healthcare costs. Furthermore, endoscopic techniques contribute to superior long-term recuperative outcomes in patients, without altering mortality rates. CONCLUSIONS: In comparison to the conventional method of craniotomy, the utilization of neuroendoscopy in the treatment of hypertensive putamen hemorrhage (HPH) may offer a more efficacious, minimally invasive, and cost-effective approach. This alternative approach has the potential to decrease the length of hospital stays and improve long-term neurologic outcomes, without altering mortality rates.

Comparison of endoscopic evacuation, craniotomy, and puncture aspiration for the treatment of spontaneous basal ganglia intracerebral hematoma.

OBJECTIVE: To compare the prognosis of patients with spontaneous basal ganglia intracerebral hematoma treated by endoscopic evacuation, craniotomy, or puncture aspiration. METHODS: This retrospective observational study included information from patients with basal ganglia hematoma who received craniotomy, endoscopic evacuation, or puncture aspiration in the Department of Neurosurgery of the First Affiliated Hospital of USTC between January 2016 and May 2021. Patients were grouped according to their treatment method for comparison. RESULTS: From a total of 184 patients, 62 cases (51 males, aged 54.44 ± 9.92 years) received craniotomy, 64 cases (45 males, aged 53.97 ± 11.87 years) received endoscopic evacuation, and 58 cases (43 males, aged 54.25 ± 10.35 years) received puncture aspiration. No significant difference was found in baseline characteristics among three surgical procedures. Patients in the endoscopy group had the shortest hospital stay (15.16 ± 4.89 days vs. 17.88 ± 5.97 and 20.77 ± 6.96 days), lowest infectious meningitis [1(1.6 %) vs. 2(3.4%) and 8(12.9%)] and pulmonary infection [3(4.7%) vs. 5(8.6%) and 13(21.0%)] rates, and highest hematoma removal rate (90.39 ± 5.22% vs. 35.87 ± 6.23 and 84.76 ± 4.91%) and Glasgow outcome scale 6 months after surgery (4.41 ± 0.53 vs. 3.74 ± 1.09 and 3.81 ± 1.03). The occurrence of gastrointestinal bleeding, epilepsy, and mortality were similar (all p > 0.05) among the groups. CONCLUSION: Patients with spontaneous basal ganglia intracerebral hematoma who received endoscopic evacuation might have better prognosis than those treated with craniotomy or puncture aspiration. In future, endoscopic surgery could become the most common method for treating spontaneous basal ganglia hemorrhages.

Accelerated Discovery of Macrocyclic CDK2 Inhibitor QR-6401 by Generative Models and Structure-Based Drug Design.

Selective CDK2 inhibitors have the potential to provide effective therapeutics for CDK2-dependent cancers and for combating drug resistance due to high cyclin E1 (CCNE1) expression intrinsically or CCNE1 amplification induced by treatment of CDK4/6 inhibitors. Generative models that take advantage of deep learning are being increasingly integrated into early drug discovery for hit identification and lead optimization. Here we report the discovery of a highly potent and selective macrocyclic CDK2 inhibitor QR-6401 (23) accelerated by the application of generative models and structure-based drug design (SBDD). QR-6401 (23) demonstrated robust antitumor efficacy in an OVCAR3 ovarian cancer xenograft model via oral administration.

Inhibition mechanism of MRTX1133 on KRASG12D: a molecular dynamics simulation and Markov state model study.

The mutant KRAS was considered as an "undruggable" target for decades, especially KRASG12D. It is a great challenge to develop the inhibitors for KRASG12D which lacks the thiol group for covalently binding ligands. The discovery of MRTX1133 solved the dilemma. Interestingly, MRTX1133 can bind to both the inactive and active states of KRASG12D. The binding mechanism of MRTX1133 with KRASG12D, especially how MRTX1133 could bind the active state KRASG12D without triggering the active function of KRASG12D, has not been fully understood. Here, we used a combination of all-atom molecular dynamics simulations and Markov state model (MSM) to understand the inhibition mechanism of MRTX1133 and its analogs. The stationary probabilities derived from MSM show that MRTX1133 and its analogs can stabilize the inactive or active states of KRASG12D into different conformations. More remarkably, by scrutinizing the conformational differences, MRTX1133 and its analogs were hydrogen bonded to Gly60 to stabilize the switch II region and left switch I region in a dynamically inactive conformation, thus achieving an inhibitory effect. Our simulation and analysis provide detailed inhibition mechanism of KRASG12D induced by MRTX1133 and its analogs. This study will provide guidance for future design of novel small molecule inhibitors of KRASG12D.

Discovery of Potent Small-Molecule Inhibitors of WDR5-MYC Interaction.

WD repeat domain 5 (WDR5) is a member of the WD40-repeat protein family that plays a critical role in multiple processes. It is also a prominent target for pharmacological inhibition in diseases such as cancer, aging, and neurodegenerative disorders. Interactions between WDR5 and various partners are essential for sustaining its function. Most drug discovery efforts center on the WIN (WDR5 interaction motif) site of WDR5 that is responsible for the recruitment of WDR5 to chromatin. Here, we describe the discovery of novel WDR5 inhibitors for the other WBM (WDR5 binding motif) pocket on this scaffold protein, to disrupt WDR5 interaction with its binding partner MYC by high-throughput biochemical screening, subsequent molecule optimization, and biological assessment. These new WDR5 inhibitors provide useful probes for future investigations of WDR5 and an avenue for targeting WDR5 as a therapeutic strategy.

The value of MGMT promote methylation and IDH-1 mutation on diagnosis of pseudoprogression in patients with high-grade glioma: A meta-analysis.

OBJECTIVE: To date, there are several published studies on the value of IDH-1 (isocitrate dehydrogenase-1) mutation and MGMT (O6-Methylguanine-DNA methyltransferas) promoter methylated status on the diagnosis of pseudoprogression (PSP) and true tumor progression after or within chemo-radiotherapy of high grade glioma (HGG). We performed a meta-analysis about the significant value of these 2 molecular markers on the diagnosis of PsP in high- grade glioma. METHODS: We searched the eligible studies from PubMed, Medline, Embase, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and Wan Fang Database. The relevant studies published before October 2018 were identified. ORs (odds ratios) with 95%CIs (confidence intervals) were used to evaluate the value using fixed- or random-effect model. RESULTS: Thirteen studies about MGMT promoter methylated status and 4 studies about IDH-1 mutations were found eligible for this present meta-analysis. Significant value of MGMT promoter methylation status (OR = 4.02, 95%CI = 2.76-5.87, P < .001) and IDH-1 mutations (OR = 12.78, 95%CI = 3.86-42.35, P < .001) were observed. CONCLUSIONS: This meta-analysis provided evidences that MGMT promoter methylation status and IDH-1 mutations could distinguish PSP from true tumor progression.

Hypoxia-Induced Cleavage Of Soluble ephrinA1 From Cancer Cells Is Mediated By MMP-2 And Associates With Angiogenesis In Oral Squamous Cell Carcinoma.

INTRODUCTION: ephrinA1 plays important roles in tumor angiogenesis. Matrix metalloproteases (MMPs) can cleave ephrinA1 from the cell membrane into extracellular environment. However, how soluble ephrinA1 is modulated by hypoxia and whether MMPs participate in this hypoxic process remains to be investigated in detail. METHODS: Thirty-seven patients with oral squamous cell carcinoma (OSCC) were included in the present study for HIF-1α, MMP-2, MMP-9 and ephrinA1 detection by immunohistochemistry. Serum samples from 35 patients were collected both preoperatively and postoperatively to confirm the existence of soluble ephrinA1 by ELISA. Block assay and Western blot analysis were further carried out to elucidate the proteolysis mechanism of ephrinA1 under hypoxic condition in vitro. RESULTS: Our data demonstrated that HIF-1α, MMP-2, MMP-9 and ephrinA1 expressed positively, and correlated with microvessel density in OSCCs, except for MMP-9. The serum expression level of ephrinA1 in OSCC patients decreased significantly after surgical removal of the solid tumors. In vitro experiments indicated that GM6001, a MMP-specific inhibitor, could reduce hypoxia-induced soluble ephrinA1 secretion from SCC cells. Further Western blot analysis confirmed that both HIF-1α and MMP-2 were up-regulated by hypoxia in a similar time-dependent manner, with the MMP-9 expression unchanged during this course. CONCLUSION: These results suggested a possible novel mechanism that ephrinA1 secretion is mediated by HIF-1α/MMP-2 signaling cascade which may play pivotal roles in OSCC neovascularization in a paracrine manner.

A Novel Drug Resistance Mechanism: Genetic Loss of Xeroderma Pigmentosum Complementation Group C (XPC) Enhances Glycolysis-Mediated Drug Resistance in DLD-1 Colon Cancer Cells.

The pro-apoptotic proteins BAX and BAK are critical regulatory factors constituting the apoptosis machinery. Downregulated expression of BAX and BAK in human colorectal cancer lead to chemotherapeutic failure and poor survival rate in patients. In this study, isogenic DLD-1 colon cancer cells and the BAX and BAK double knockout counterpart were used as the cellular model to investigate the role of BAX/BAK-associated signaling network and the corresponding downstream effects in the development of drug resistance. Our data suggested that DLD-1 colon cancer cells with BAX/BAK double-knockout were selectively resistant to a panel of FDA-approved drugs (27 out of 66), including etoposide. PCR array analysis for the transcriptional profiling of genes related to human cancer drug resistance validated the altered level of 12 genes (3 upregulated and 9 downregulated) in DLD-1 colon cancer cells lack of BAX and BAK expression. Amongst these genes, XPC responsible for DNA repairment and cellular respiration demonstrated the highest tolerance towards etoposide treatment accompanying upregulated glycolysis as revealed by metabolic stress assay in DLD-1 colon cancer cells deficient with XPC. Collectively, our findings provide insight into the search of novel therapeutic strategies and pharmacological targets to against cancer drug resistance genetically associated with BAX, BAK, and XPC, for improving the therapy of colorectal cancer via the glycolytic pathway.

Comparison of clinical outcomes of expansive open-door laminoplasty with unilateral or bilateral fixation and fusion for treating cervical spondylotic myelopathy: a multi-center prospective study.

BACKGROUND: The present study evaluated the clinical outcomes and safety of expansive open-door laminoplasty, when securing with C4 - C6 lateral mass screw and fusion. METHODS: A total of 110 patients with cervical spondylotic myelopathy (CSM) were enrolled. There were 88 male and 22 female, with mean age at 60.55 ± 10.95 years. All of the patients underwent expansive open-door laminoplasty with unilateral or bilateral C4-6 lateral mass screws fixation and fusion. Clinical data, including age, gender, operation-related information, pre- and post-operation Japanese Orthopedic Association (JOA) scores, and cervical curvatures were collected. RESULTS: The mean follow-up time of the cohort was 13.61 ± 9.53 months. Among the 110 patients, 33 of them were allocated to Unilateral group, and 77 of them were in Bilateral group. The mean JOA score of the 110 patients before surgery was 10.07 ± 2.39, and the score was improved significantly to 12.85 ± 2.45 after surgery. There were no reported cases of neurological deterioration or symptom worsening. Patients in both the Unilateral group and Bilateral groups had significant improvement of JOA scores. Among all patients, the most frequently observed complications were axial symptoms (n = 7). The average preoperative cervical curvature among all patients was 15.17 ± 5.26, and the post-surgery curvature was 14.41 ± 4.29. Similar observations were found between Unilateral and Bilateral groups. CONCLUSION: The modified surgical approach provided satisfactory clinical outcome in patients with CSM. The unilateral and bilateral fixation appeared to provide similar outcomes, in terms of cervical curvature maintenance and improvement of clinical symptoms. However, the examination of the exact differences between the two fixation methods await further biomechanical studies.

[The study of combined unilateral intraoral and extraoral reduction approach in the treatment of anterior temporo-mandibular joint dislocation].

OBJECTIVE: To observe the clinical outcomes of a combined unilateral intraoral and extraoral reduction approach in the treatment of anterior temporomandibular joint (TMJ) dislocation. METHODS: Postural muscular chains were utilized in the biomechanical analysis of stomatognathic systems for improving TMJ repositioning approaches. A total of 87 patients with anterior TMJ dislocation were included in the present study. A combined unilateral intraoral and extraoral reduction approach was applied, and the clinical effects were evaluated. RESULTS: Biomechanical analysis reveal that reflexive contrac-tion of the maxillary muscle group was blocked sufficiently during the combined unilateral intraoral and extraoral reduction process. All dislocated TMJs were set successfully and efficiently with few complications. CONCLUSIONS: Combined unilateral intraoral and extraoral reduction approach is an effective, convenient, and minimally invasive way to treat anterior TMJ dislo-cations.

Composition of dissolved organic matter controls interactions with La and Al ions: Implications for phosphorus immobilization in eutrophic lakes.

Applications of aluminium (Al) salt or lanthanum (La) modified bentonite (LMB) have become popular methodologies for immobilizing phosphorus (P) in eutrophic lakes. The presence of humic substances, has been shown to inhibit this form of treatment due to the complexation with La/Al. However, the effects of other dissolved organic matter (DOM), especially that derived from phytoplankton (the dominant source in eutrophic lakes) are unknown. In this study, the interaction with La/Al of Suwannee River Standard Humic Acid Standard II (SRHA) and algae-derived DOM (ADOM) were investigated and compared. Differed to SRHA which was dominated by polyphenol-like component (76.8%, C1-SRHA), majority in ADOM were protein-like substance, including 41.9% tryptophan-like component (C2-ADOM) and 21.0% tyrosine-like component (C3-ADOM). Two reactions of complexation and coprecipitation were observed between SRHA/ADOM and La/Al. Complexation dominated at low metal inputs less than 10 µM and coprecipitation was the main reaction at higher metal inputs. For ADOM, the tryptophan-like component (C2-ADOM) was the important component to react with metal. The reaction rate for C2-ADOM with La were about two-third of that for C1-SRHA, indicating that the influence of C2-ADOM was significant during the P immobilization by La/Al-based treatment in eutrophic lakes. The P removal data in the presence of ADOM confirmed the significant inhibition of ADOM. In addition, based on the composition of coprecipitates and relatively biodegradable character of tryptophan-like substances (C2-ADOM), the coprecipitation of ADOM was assumed to reduce the stability of precipitated P in eutrophic lakes. The release of P from the potential biodegradation of the coprecipitates and thus the possible decline of the performance of P immobilization by La/Al-based treatments is an important work in the future.

Effects of lentivirus-mediated CYP17A1 gene silencing on the biological activity of glioma.

Gliomas are the most common malignant primary brain tumors with poor prognosis. We attempted to explore the role of CYP17A1 in glioma progression. We demonstrated that the expression of CYP17A1 was significantly higher in the glioma tissues than the normal brain tissues, especially in malignant glioma. Moreover, the expression of CYP17A1 gene was positively correlative with glioma pathological grades. In vitro, CYP17A1 gene silence inhibited the proliferation and invasion of glioma cells and promoted the apoptosis in glioma cells. Also, the subcutaneously transplanted tumour in BALB/C-nu showed that CYP17A1 gene silence inhibited glioma growth. These results reveal that CYP17A1 plays a major role in the progress of glioma.

2-Aminoethoxydiphenylborane sensitizes anti-tumor effect of bortezomib via suppression of calcium-mediated autophagy.

Non-small-cell lung cancer (NSCLC) accounts for most lung cancer cases. Therapeutic interventions integrating the use of different agents that focus on different targets are needed to overcome this set of diseases. The proteasome system has been demonstrated clinically as a potent therapeutic target for haematological cancers. However, promising preclinical data in solid tumors are yet to be confirmed in clinics. Herein, the combinational use of Bortezomib (BZM) and 2-aminoethoxydiphenylborane (2-APB) toward NSCLC cells was studied. We confirmed that BZM-triggered cytoprotective autophagy that may counteract with the cytotoxic effects of the drug per se. 2-APB was selected from screening of a commercial natural compounds library, which potentiated BZM-induced cytotoxicity. Such an enhancement effect was associated with 2-APB-mediated autophagy inhibition. In addition, we revealed that 2-APB suppressed calcium-induced autophagy in H1975 and A549 NSCLC cells. Interestingly, BZM [0.3 mg/kg/3 days] combined with 2-APB [2 mg/kg/day] significantly inhibited both primary (around 47% tumor growth) and metastatic Lewis lung carcinoma after a 20-day treatment. Our results suggested that BZM and 2-APB combination therapy can potentially be developed as a novel formulation for lung cancer treatment.

Irisin Alleviates Advanced Glycation End Products-Induced Inflammation and Endothelial Dysfunction via Inhibiting ROS-NLRP3 Inflammasome Signaling.

The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome have been implicated in the initiation or progression of atherosclerosis. Recent research showed that irisin, a newly discovered adipomiokine, alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses, suggesting that irisin may be a promising candidate for the treatment of vascular complications of diabetes. However, the association between irisin and NLRP3 inflammasome in the pathogenesis of atherosclerosis remains unclear. In the present study, we cultured human umbilical vein endothelial cells (HUVECs) in advanced glycation end products (AGEs) medium; exogenous irisin (0.01, 0.1, 1 µg/ml) were used as an intervention reagent. siRNA and adenoviral vector were constructed to realize silencing and over-expression of NLRP3 gene. Our data showed that irisin significantly reversed AGEs-induced oxidative stress and NLRP3 inflammasome signaling activation (p < 0.05), and increased the endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production in a dose-dependent manner (p < 0.05). siRNA-mediated knockdown NLRP3 facilitated the irisin-mediated anti-inflammatory and antiatherogenic effects (p < 0.05). However, these irisin-mediated effects were reversed by over-expression NLRP3 (p < 0.05). Taken together, our results reveal that irisin alleviates AGEs-induced inflammation and endothelial dysfunction via inhibiting ROS-NLRP3 inflammasome signaling, suggest a likely mechanism for irisin-induced therapeutic effect in vascular complications of diabetes.

The diagnostic accuracy of HE4 in lung cancer: a meta-analysis.

The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of serum HE4 for lung cancer. We conducted a comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. A total of seven articles including 715 cases and 549 controls were included for analysis. The summary estimates for serum HE4 in the diagnosis of lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68-0.75), SPE 0.85 (95% CI: 0.81-0.88), PLR 4.68 (95% CI: 3.23-6.78), NLR 0.31 (95% CI: 0.24-0.39), and DOR 17.14 (95% CI: 9.72-30.20), and the area under the curve (AUC) was 0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the diagnosis of lung cancer. In addition, considering the high heterogeneity and potential publication bias, further studies with rigorous design and large sample size are needed in the future.

Advanced glycation endproducts regulate smooth muscle cells calcification in cultured HSMCs.

OBJECTIVE: To investigate the mechanism of Advanced glycation end products (AGEs) promoting the calcification of smooth muscle cells. METHODS: The successfully cultured smooth muscle cells were divided into three groups: normal culture group (group A), calcified culture group (group B), calcification + AGEs group (group C); the concentration of intracellular calcium ion was detected in each group; the promotion of AGEs on the calcification of HSMCs was confirmed by VON KOSSA staining; and the expressions of ß-catenin, RAGE, ß-catenin, OPG and E-cadherin protein were detected by immunofluorescence and western blot. RESULTS: The morphology of the cells in each group showed that the amount of calcified plaques in calcification + AGES group were significantly higher than the calcification group. VON KOSSA staining showed that with increasing concentrations of AGE-BSA, the amount of its calcification gradually increased. Calcium concentration in Calcification + 20 mg/L AGEs group was significantly higher, followed by 40 mg/L AGEs group. The expression of ß-catenin increased with the increasing concentrations of AGEs. CONCLUSION: AGEs can promote the calcification of human femoral artery smooth muscle cells, with a concentration gradient effect. With increasing concentrations of AGEs, the expression of RAGE increased, indicating that AGEs-induced HSMCs proliferation was correlated with RAGE expression.

Diagnostic role of circulating YKL-40 in endometrial carcinoma patients: a meta-analysis of seven related studies.

In the past decade, several studies have suggested a possible link between circulating YKL-40 levels and endometrial carcinoma (EC), but have arrived at inconsistent results. Therefore, we conducted the present meta-analysis and aim to disclose a more comprehensive evaluation of the sensitivity, specificity, and diagnostic accuracy of YKL-40 in EC. We systematically searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure databases for studies that evaluated the diagnostic value of YKL-40 in endometrial cancer. The STATA software 12.0 and Meta-Disc software were used to test the heterogeneity and to evaluate the overall test performance. A total of seven studies including 234 EC cases and 300 controls were included in our meta-analysis. The summary estimates of YKL-40 for EC diagnosis indicated a moderately high diagnostic accuracy for circulating YKL-40, with a sensitivity of 0.74, a specificity of 0.87, a PLR of 5.74, a NLR of 0.30, a DOR of 19.14, and an AUC of 0.80. On the basis of our meta-analysis, therefore, circulating YKL-40 could be promising and meaningful in the diagnosis of EC.

Aluminum induces rapidly mitochondria-dependent programmed cell death in Al-sensitive peanut root tips.

BACKGROUND: Although many studies suggested that aluminum (Al) induced programmed cell death (PCD) in plants, the mechanism of Al-induced PCD and its effects in Al tolerance is limited. This study was to investigate the mechanism and type of Al induced PCD and the relationship between PCD and Al tolerance. RESULTS: In this study, two genotypes of peanut 99-1507 (Al tolerant) and ZH2 (Al sensitive) were used to investigate Al-induced PCD. Peanut root growth inhibition induced by AlCl3 was concentration and time-dependent in two peanut varieties. AlCl3 at 100 µM could induce rapidly peanut root tip PCD involved in DNA cleavage, typical apoptotic chromatin condensation staining with DAPI, apoptosis related gene Hrs203j expression and cytochrome C (Cyt c) release from mitochondria to cytosol. Caspase3-like protease was activated by Al; it was higher in ZH2 than in 99-1507. Al increased the opening of mitochondrial permeability transition pore (MPTP), decreased inner membrane potential (ΔΨm) of mitochondria. Compared with the control, Al stress increased O2•- and H2O2 production in mitochondria. Reactive oxygen species (ROS) burst was produced at Al treatment for 4 h. CONCLUSIONS: Al-induced PCD is earlier and faster in Al-sensitive peanut cultivar than in Al-tolerant cultivar. There is a negative relationship between PCD and Al resistance. Mitochondria- dependence PCD was induced by Al and ROS was involved in this process. The mechanism can be explained by the model of acceleration of senescence under Al stress.