Leptin Mediates Prostate Stromal Cell Proliferation, Smooth Muscle Contraction, and Mitochondrial Function in Benign Prostate Hyperplasia.

Introduction: Leptin is a metabolic peptide hormone produced by adipocytes, with proven roles in proliferation of prostate cancer cells and of prostate cells in animal models of benign prostatic hyperplasia (BPH). Thus, the role of leptin as a molecular link connecting BPH and lower urinary tract symptoms (LUTS) suggestive of BPH with metabolic symptoms appears feasible but is still unknown. In fact, a connection between metabolic syndrome and BPH is becoming increasingly evident from epidemiologic studies. Key factors of Lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS) are increased prostate smooth muscle tone, and prostate enlargement. Here, we examined the effects of leptin on contraction of human prostate smooth muscle and on growth of stromal cells. Methods: We performed microarray analysis to identify genes (fold change ≥ 1.5) associated with BPH/LUTS progression, such as those involved in proliferation, apoptosis, and mitochondrial metabolism, in rat prostate tissue (data from GSE129561). We then used electric field stimulation (EFS) to induce frequency-dependent, neurogenic contractions of human prostate strips, which were enhanced by leptin. We also examined the effect of leptin on human prostate stromal cells (WPMY-1) and found increased cell proliferation and viability upon exposure. To explore the underlying mechanism, we conducted mitochondrial stress assay using near-infrared (NIR) fluorescent dye and flow cytometry (FACS) analysis and observed reduced cellular apoptosis and preserved mitochondrial membrane potential (∆ψM) after leptin treatment. Results: Microarray analysis reveals that leptin regulates prostate smooth muscle contraction and stromal cell proliferation, shedding new light on its involvement in BPH/LUTS pathogenesis and mitochondrial function. We found that leptin enhanced the proliferation rate of prostate stromal cells relative to the control group (0.67 ± 0.05 vs 0.54 ± 0.08, p-value= 0.024). Moreover, leptin (100 ng/mL) potentiated the frequency-dependent, neurogenic contractions of prostate strips elicited by EFS (p= 0.047 between leptin and control group). We also show that leptin treatment increased the mitochondrial membrane potential of prostate stromal cells and inhibited mitochondrial apoptosis. Discussion: Our results indicate that leptin stimulates the contractility and proliferation of smooth muscle and stromal cells in the human prostate, implying a potential role for leptin in exacerbating BPH/LUTS in obese men. Leptin modulation may be a beneficial therapeutic strategy for patients with metabolic syndrome and BPH/LUTS. Further studies are warranted to elucidate the mechanisms and implications of the leptin system in BPH/LUTS.

PCMT1 regulates the migration, invasion, and apoptosis of prostate cancer through modulating the PI3K/AKT/GSK-3ß pathway.

Protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is a repair enzyme that catalyzes the conversion of isomerized aspartic acid (iso-Asp) residues into their normal structure, thereby restoring the configuration and function of proteins. Studies have shown that PCMT1 is overexpressed in several tumors and affects patients' prognosis. However, there are few reports on the role of PCMT1 in prostate cancer (PCa). In the present research, with the assistance of The Cancer Genome Atlas Program (TCGA) database, we found that PCMT1 was overexpressed in PCa tissues. The results of quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry staining also showed that PCMT1 expression was significantly increased in PCa tissues and cell lines. In PCa clinical samples, PCMT1 expression was closely related to Gleason score, clinical stage, lymph node metastasis and bone metastasis. The experiments of overexpression and knockdown of PCMT1 in vitro or in vivo showed that PCMT1 can significantly promote the proliferation, migration and invasion of PCa cells, inhibit cell apoptosis, and promote the growth of PCa. We furthermore confirmed that PCMT1 regulated the migration, invasion and apoptosis of PCa cells by modulating the phosphatidylinositol 3-kinase/AKT kinase/glycogen-synthase kinase-3ß (PI3K/AKT/GSK-3ß) signaling pathway. Collectively, PCMT1 plays a cancer-facilitative role in PCa by promoting the proliferation, migration and invasion of PCa cells, and inhibiting apoptosis. Therefore, PCMT1 is considered to represent a novel target for treating PCa.

Effect of Long-Term Aging on Fatigue and Thermal Cracking Performance of Polyphosphoric Acid and Styrene-Butadiene-Styrene-Modified Bio-Blend Bitumen.

Polyphosphoric acid (PPA) and styrene-butadiene-styrene (SBS) were adopted to produce PPA-SBS-modified bio-blend bitumen, which achieved excellent mechanical performance. However, its long-range performance, such as the fatigue and thermal cracking behavior under long-term thermal oxidation, is not well understood. Therefore, a pressure aging vessel (PAV) system was applied to simulate the aging behavior of the bitumen under the action of thermal oxidation. Then, a linear amplitude sweep (LAS) test combined with a viscoelastic continuum damage (VECD) model was applied to investigate the fatigue properties of the bitumen. Moreover, a bending beam rheometer (BBR) test was conducted to evaluate the thermal cracking resistance of the bitumen before and after PAV aging. Meanwhile, an atomic force microscope (AFM) was applied to observe the microscopic topography. The results show that the original compound-modified bitumen can bear more fatigue damage than that of the control bitumen at the failure point, and it also has excellent fatigue resistance at 2.5%, 5%, 7.5%, and 10% applied strain. Moreover, the VECD model can accurately predict the fatigue life of the bitumen under different applied strains. The variation ratio of stiffness modulus for the compound-modified bitumen is below that of the control bitumen after PAV aging, so it shows a better anti-aging performance. Finally, the AFM test shows that PPA and bio-bitumen decrease the heterogeneity of the bitumen, reducing the difference between phases.

Effect of heating history on the emission of volatile organic compounds from asphalt materials.

Asphalt binders release hazardous fumes during high-temperature heating that severely endanger human health and pollute the environment. In this study, a volatile organic compound (VOC) generation and detection device comprising a portable VOC detector was developed, and two heating modes (intermittent and continuous heating) were established to explore the influence of heating history on the VOC emission behavior of five asphalt samples. The changes in the VOC species and content, as determined by the heating history, were analyzed via gas chromatography-mass spectrometry (GC-MS). Finally, the key factors affecting the emission of VOCs from asphalt are discussed based on the four components of asphalt materials. The results indicated that the emission of VOCs from asphalt materials under intermittent heating conditions decreased significantly with increasing heating history (significantly fewer VOCs, including 13 common components such as alkanes, benzenes, and hydrocarbon derivatives, were emitted under this condition than under continuous heating conditions at the same temperature point). Compared with continuous heating, intermittent heating is more conducive for studying asphalt VOCs. Under intermittent heating, different asphalt materials exhibited similar VOC emission curves; the VOCs were mainly emitted during the first two heating stages (200 and 180 °C, respectively). Thus, it can be deduced that asphalt VOC emissions were induced by the synchronized actions of the four components of asphalt materials. Therefore, different components can contribute to the emission of several VOCs of the same composition. The heavy and light components mainly facilitate the emission of common components with carbon atomic numbers <18 and > 18, respectively.

Study on the Conventional Performance and Microscopic Properties of PPA/SBS-Modified Bio-Mixed Asphalt.

To promote the construction of environmentally friendly, sustainable pavements and solve the impact of the scarcity of asphalt resources on highway development, bio-mixed asphalt (BMA) modified by SBS and polyphosphoric acid (PPA) was prepared, and the influence of the ratio of bio-asphalt (BA) replacing petroleum asphalt on different PPA/SBS blending schemes was explored through conventional property tests. According to each PPA/SBS blending scheme, the optimal replacement ratio of bio-asphalt was optimized, and the microstructure and distribution morphology of different PPA/SBS-modified BMA were evaluated. Conventional property test results show that with the same PPA/SBS content, the replacement ratio of bio-asphalt has a significant impact on the conventional performance of composite-modified asphalt, but the appropriate replacement ratio of bio-asphalt can improve the storage stability and conventional performance of composite-modified asphalt; in micromorphological analysis, it was found that the number of bee-like structures on the surface of the modified BMA decreased significantly, which indicated that the molecular heterogeneity of various components in the asphalt was reduced. In addition, bio-asphalt changed the particle morphology and improved the dispersity of SBS in asphalt. The composite-modified BMA had a lower SBS content, but its conventional performance was still excellent-so it has significant application prospects in road engineering.

MicroRNA-1246 regulates proliferation, invasion, and differentiation in human vascular smooth muscle cells by targeting cystic fibrosis transmembrane conductance regulator (CFTR).

MicroRNA (miRNA) plays a key role in the proliferation and invasion of vascular smooth muscle cells (VSMCs). However, the role and underlying mechanism of miRNAs in VSMCs are not fully understood. Therefore, this study was designed to investigate the role and mechanism of microRNA-1246 (miR-1246) in VSMCs. VSMCs were cultured, and the proliferation of VSMCs was stimulated by platelet-derived growth factor (PDGF-BB) or 15% fetal bovine serum (FBS). The quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression levels of miR-1246 and cystic fibrosis transmembrane conductance regulator (CFTR) in VSMCs. The CCK-8 assay and transwell assay were used to detect the proliferation and invasion of VSMCs. Target gene prediction and screening and luciferase reporter assays were used to verify downstream target genes of miR-1246. Western blotting was used to detect the protein expression levels of PCNA, α-SMA, SM-MHC, Collagen-1, and Cyclin D1 in VSMCs. PDGF-BB and FBS treatment induced VSMCs proliferation and the upregulation of miR-1246 expression. Overexpression of miR-1246 promoted VSMCs proliferation, invasion, and differentiation towards synthetic phenotype, while knockdown of miR-1246 had opposite effects. In addition, CFTR was found to be a direct target for miR-1246, and miR-1246 inhibited the expression of CFTR. Moreover, overexpression of CFTR inhibited VSMC proliferation and synthetic differentiation, while overexpression of miR-1246 partly abolished the effects of CFTR overexpression on VSMCs proliferation and differentiation. Our data suggest that MiR-1246 promotes VSMC proliferation, invasion, and differentiation to synthetic phenotype by regulating CFTR. MiR-1246 may be a potential therapeutic target for atherosclerosis.

Fibronectin modified TiO2 nanotubes modulate endothelial cell behavior.

Cardiovascular disease has become a great threat to the health of mankind; current titanium (Ti) stents fail due to late stent thrombosis caused by the lack of re-endothelialization of the Ti stent. The objective of this study was to design a novel cardiovascular Ti implant with improved surface biocompatibility. TiO2 nanotubes with a diameter of 110 nm were anodized at a constant voltage of 30 V, and fibronectin was immobilized onto the TiO2 nanotubes using polydopamine. The element composition, morphology, and wettability of the different substrate surfaces were characterized by x-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), and contact angle measurements, respectively, confirming the successful immobilization of fibronectin. In vitro experiments including immunofluorescence staining, Cell Counting Kit-8 (CCK-8), and nitric oxide (NO) and prostacyclin (PGI2) release demonstrate that fibronectin modified TiO2 nanotubes supported cell adhesion, proliferation, and normal cellular functions of human umbilical vein endothelial cells (HUVECs). These methodologies can be applied for future fabrication of cardiovascular stents.

A new, short-recorded photoplethysmogram dataset for blood pressure monitoring in China.

Open clinical trial data provide a valuable opportunity for researchers worldwide to assess new hypotheses, validate published results, and collaborate for scientific advances in medical research. Here, we present a health dataset for the non-invasive detection of cardiovascular disease (CVD), containing 657 data segments from 219 subjects. The dataset covers an age range of 20-89 years and records of diseases including hypertension and diabetes. Data acquisition was carried out under the control of standard experimental conditions and specifications. This dataset can be used to carry out the study of photoplethysmograph (PPG) signal quality evaluation and to explore the intrinsic relationship between the PPG waveform and cardiovascular disease to discover and evaluate latent characteristic information contained in PPG signals. These data can also be used to study early and noninvasive screening of common CVD such as hypertension and other related CVD diseases such as diabetes.

Comparison of the Therapeutic Effects of Acupuncture at PC6 and ST36 for Chronic Myocardial Ischemia.

We aimed to compare the differences of the effects on chronic myocardial ischemia (MI) of acupuncture at PC6 and ST36. The chronic MI model of minipigs was created by implanting an Ameroid constrictor on the left anterior descending coronary artery (LAD) and then two weeks' acupuncture was stimulated at PC6 or ST36, respectively. The results showed that both acupoints' stimulation decreased the serous cardiac troponin T (cTnT) and ischemia modified albumin (IMA) significantly and improved the ischemic ECG changes. The amplitude of pathological Q wave in the PC6 group decreased more significantly than that of the ST36 group. The cardiovascular magnetic resonance imaging (cMRI) results showed that the decreased left ventricular ejection fraction (LVEF) was not improved obviously in both groups. The left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) enlarged progressively even after acupuncture. The left ventricular wall mass (LVWM) in the ST36 group increased more obviously than that of the PC6 group, which paralleled the decreasing angiotensin II (Ang II) concentration in the plasma. These results suggested that acupuncture at PC6 or ST36 was effective for protecting the myocardium from chronic ischemic injury, and the effect of PC6 seemed to be better.

[Study on aided diagnosis for cardiovascular diseases based on Relief algorithm].

The study was intended to introduce a novel method for aided diagnosis of cardiovascular diseases based on photoplethysmography (PPG). For this purpose, 40 volunteers were recruited in this study, of whom the physiological and pathological information was collected, including blood pressure and simultaneous PPG data on fingertips, by using a sphygmomanometer and a smart fingertip sensor. According to the PPG signal and its first and second derivatives, 52 features were defined and acquired. The Relief feature selection algorithm was performed to calculate the contribution of each feature to cardiovascular diseases. And then 10 core features which had the greatest contribution were selected as an optimal feature subset. Finally, the efficiency of the Relief feature selection algorithm was demonstrated by the results of k-nearest neighbor (kNN) and support vector machine (SVM) classifier applications of the features. The prediction accuracy of kNN model and SVM reached 66.67% and 83.33% respectively, indicating that: ① Age was the foremost feature for aided diagnosis of cardiovascular diseases; ② The optimal feature subset provided an important evaluation of cardiovascular health status. The obtained results showed that the application of the Relief feature selection algorithm provided high accuracy in aided diagnosis of cardiovascular diseases.

Dexmedetomidine preconditioning inhibits the long term inflammation induced by renal ischemia/reperfusion injury in rats.

PURPOSE: To investigate the protective effects of dexmedetomidine (Dex) against renal ischemia/reperfusion injury (IRI). METHODS: Sprague-Dawley rats were randomly divided to sham group, IRI group and Dex group. The SD rats were subjected to 45 min of ischemia followed by eight weeks of reperfusion. Prior to ischemia, rats were either treated with Dex or not. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. Immunohistochemistry was performed for CD3 T-cell infiltrates. Real-time PCR and western blot were detected for the expression of TNF-α, IL-1ß, ICAM-1, HMGB1 and TLR4. RESULTS: Compared with sham group, renal IRI significantly increased the serum levels of BUN and Cr. The H&E staining indicated that renal IRI resulted in obvious renal injury and immunohistochemistry found that there were more CD3 T-cell infiltrates in IRI group. Also, renal IRI upregulated the expression of TNF-α, IL-1ß, ICAM-1, HMGB1 and TLR4. However, all these changes were alleviated by the treatment with Dex. CONCLUSIONS: Dexmedetomidine has beneficial effects on long term inflammation induced by renal ischemia/reperfusion injury. Its mechanisms may be achieved through inhibiting the HMGB1/TLR4 pathway to exert protective effects.

Dexmedetomidine preconditioning inhibits the long term inflammation induced by renal ischemia/reperfusion injury in rats

PURPOSE: To investigate the protective effects of dexmedetomidine (Dex) against renal ischemia/reperfusion injury (IRI). METHODS: Sprague-Dawley rats were randomly divided to sham group, IRI group and Dex group. The SD rats were subjected to 45 min of ischemia followed by eight weeks of reperfusion. Prior to ischemia, rats were either treated with Dex or not. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. Immunohistochemistry was performed for CD3 T-cell infiltrates. Real-time PCR and western blot were detected for the expression of TNF-α, IL-1β, ICAM-1, HMGB1 and TLR4. RESULTS: Compared with sham group, renal IRI significantly increased the serum levels of BUN and Cr. The H&E staining indicated that renal IRI resulted in obvious renal injury and immunohistochemistry found that there were more CD3 T-cell infiltrates in IRI group. Also, renal IRI upregulated the expression of TNF-α, IL-1β, ICAM-1, HMGB1 and TLR4. However, all these changes were alleviated by the treatment with Dex. CONCLUSIONS: Dexmedetomidine has beneficial effects on long term inflammation induced by renal ischemia/reperfusion injury. Its mechanisms may be achieved through inhibiting the HMGB1/TLR4 pathway to exert protective effects.

[Effect of Needle Embedded in Neiguan (PC6) on Changes of ECG in Chronic Myocardial Ischemia Model Mini-pigs].

Objective To observe the effect of needle embedded in Neiguan (PC6) on electro- cardiogram (ECG) changes in model mini-pigs with chronic myocardial ischemia. Methods The protein shrink narrow ring (Ameroid Ring) was placed in the proximal part of the left coronary anterior descend- ing branch of 12 Chinese mini-pigs to prepare animal model. One died during the modeling. Chronic myo- cardial ischemia mini-pig models were established after 4 weeks. Successfully modeled 11 mini-pigs were divided into the test group (n =6) and the control group (n =5). Needle were embedded in Neiguan (PC6) of the test group and Zusanli (ST36) of the control group at week 4 after modeling. Electroacupuncture (EA) at corresponding acupoint twice (once before embedding and at week 2 after embedding) , 20 min each time. Changes of Q wave of ECG, heart rate, and ST-T interval were observed in the two groups be- fore and after modeling, before and after EA. Results Compared with before modeling in the same group, the absolute value of Q wave both increased in the two groups after modeling (P <0. 05, P <0. 01J. No statistical difference existed in heart rate in the two groups between before and after modeling (P> 0. 05). Compared with before needling in the same group, ST-T interval was prolonged in the test group (P <0. 05). Compared with the control group at the same time point, the absolute value of Q wave was re- duced before EA, ST-T interval was prolonged after EA in the test group (P <0. 05). No statistical differ- ence existed in heart rate between the control group and the test group before EA (P >0. 05). Conclusion Needle embedded in Neiguan (PC6) could arrive at therapeutic effect of myocardial ischemia possibly through improving myocardial blood supply.

Downregulation of cold-inducible RNA-binding protein activates mitogen-activated protein kinases and impairs spermatogenic function in mouse testes.

Cold-inducible RNA-binding protein (CIRP) is an RNA-binding protein that is expressed in normal testes and downregulated after heat stress caused by cryptorchidism, varicocele or environmental temperatures. The purpose of this study was to investigate the functions of CIRP in the testes. We employed RNAi technique to knock down the expression of CIRP in the testes, and performed haematoxylin and eosin staining to evaluate morphological changes following knockdown. Germ cell apoptosis was examined by terminal deoxynucleotidal transferase-mediated dUTP nick end labelling (TUNEL) assay, and mitogen-activated protein kinase (MAPK) signalling pathways were investigated by Western blotting to determine the possible mechanism of apoptosis. We found that using siRNA is a feasible and reliable method for knocking down gene expression in the testes. Compared to controls, the mean seminiferous tubule diameter (MSTD) and the thickness of the germ cell layers decreased following siRNA treatment, whereas the percentage of apoptotic seminiferous tubules increased. The p44/p42, p38 and SAPK/JNK MAPK pathways were activated after downregulation of CIRP. In conclusion, we discovered that downregulation of CIRP resulted in increased germ cell apoptosis, possibly via the activation of the p44/p42, p38 and SAPK/JNK MAPK pathways.