OBJECTIVETo explore the distribution, combination and evolution of various syndromic etiologies of erectile dysfunction (ED) based on the syndrome etiology theory.

METHODSUsing the ED Syndromic Etiology Scale, we collected the clinical data on the Chinese medicine diagnoses of 297 cases of ED, extracted the core syndromic etiologies by analysis of principal components and factors, and analyzed the patterns of distribution, combination, and evolution of ED syndromic etiologies according to the general information of the patients.

RESULTSThrough analysis of principal components and factors, 9 core syndromic etiologies were extracted, i. e. , liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, blood stasis, kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, and phlegm-damp. Each of these syndrome etiologies exhibited its own specific distribution patterns. Of the total number of cases studied, 51.52% had 2 or 3 core syndromic etiologies and 36.03% had only one.

CONCLUSIONIn the early stage of ED, its syndromic etiologies are usually liver constraint with qi stagnation, kidney yin deficiency, damp-heat, liver constraint transforming into liver-fire, and blood stasis. With the natural progres- sion of the disease, its syndromic etiologies gradually evolve into kidney yang deficiency, heart-spleen paired deficiency, qi-yin paired deficiency, phlegm-damp, and blood stasis, and finally into yin-yang deficiency of the heart, spleen and kidneys, combined with phlegm-damp and blood stasis.

Adult ; Erectile Dysfunction ; diagnosis ; drug therapy ; etiology ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged

OBJECTIVETo investigate the cytotoxic mechanism of cadmium (Cd) on cerebral cortical neurons.

METHODSThe primary cultures of rat cerebral cortical neurons were treated with different concentrations of cadmium acetate (0, 5, 10, and 20 micromol/L), and then the cell viability, apoptosis, ultrastructure, intracellular [Ca2+], and reactive oxygen species (ROS) levels, mitochondrial membrane potential (delta psi), activities of catalase (CAT) and superoxide dismutase (SOD) were measured.

RESULTSA progressive loss in cell viability and an increased number of apoptotic cells were observed. In addition, Cd-induced apoptotic morphological changes in cerebral cortical neurons were also demonstrated by Hoechst 33258 staining. Meanwhile, ultrastructural changes were distortion of mitochondrial cristae and an unusual arrangement. Simultaneously, elevation of intracellular [Ca2+]i and ROS levels, depletion of Delta Psi were revealed in a dose-dependent manner during the exposure. Moreover, CAT and SOD activities in the living cells increased significantly.

CONCLUSIONExposure of cortical neurons to different doses of Cd led to cellular death, mediated by an apoptotic mechanism, and the apoptotic death induced by oxidative stress may be a potential reason. And the disorder of intracellular homeostasis caused by oxidative stress and mitochondrial dysfunction may be a trigger for apoptosis in cortical neurons.

Animals ; Apoptosis ; drug effects ; Cadmium ; toxicity ; Cerebral Cortex ; cytology ; drug effects ; metabolism ; In Vitro Techniques ; Neurons ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism

The hypertension is one of chronic vascular diseases, which often implicates multiple tissues causing stroke, cardiac hypertrophy, and renal failure. A growing body of evidence suggests that inflammatory mechanisms are important participants in the pathophysiology of hypertension. In this study, the inflammatory status of these tissues (kidney, liver, heart, and brain) in spontaneously hypertensive rats (SHR) was analyzed and its molecular mechanism was explored. The tissues were dissected from SHR and age-matched control Wistar-Kyoto (WKY) rats to investigate the abundance of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma). mRNA levels were determined by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blot. To evaluate the oxidative stress of tissues, carbonyl protein content and total antioxidant capacity of tissues were detected by spectrophotometry and ferric reduction ability power (FRAP) method. The results suggest that: (1) Expressions of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma) in SHR were higher compared with those in WKY rats except no evident increase of IL-1beta mRNA in liver and brain in SHR. (2) Tissues in SHR contained obviously increased carbonyl protein (nmol/mg protein) compared to that in WKY rats (8.93+/-1.08 vs 2.27+/-0.43 for kidney, 2.23+/-0.23 vs 0.17+/-0.02 for heart, 13.42+/-1.10 vs 5.72+/-1.01 for brain, respectively, P<0.05). However, no evident difference in the amount of carbonyl protein in liver was detected between SHR and WKY rats. (3) Total antioxidant capacities of kidney, liver, heart and brain were markedly lower in SHR than that in WKY rats (P<0.05). Thus, the present data reveal a higher inflammatory status in the important tissues in SHR and indicate that inflammation might play a potential role in pathogenesis of hypertension and secondary organ complications.
Animals ; Brain ; metabolism ; pathology ; Cytokines ; genetics ; metabolism ; Hypertension ; pathology ; Inflammation ; pathology ; Interleukin-1beta ; genetics ; metabolism ; Kidney ; metabolism ; pathology ; Male ; Myocardium ; metabolism ; pathology ; Oxidative Stress ; immunology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

To investigate 1alpha,25-(OH)2D3 regulation of matrix metalloproteinase-9 (MMP-9) protein expression during osteoclast formation and differentiation, receptor activator of nuclear factor kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) were administered to induce the differentiation of RAW264.7 cells into osteoclasts. The cells were incubated with different concentrations of 1alpha,25-(OH)2D3 during culturing, and cell proliferation was measured using the methylthiazol tetrazolium method. Osteoclast formation was confirmed using tartrate-resistant acid phosphatase (TRAP) staining and assessing bone lacunar resorption. MMP-9 protein expression levels were measured with Western blotting. We showed that 1alpha,25-(OH)2D3 inhibited RAW264.7 cell proliferation induced by RANKL and M-CSF, increased the numbers of TRAP-positive osteoclasts and their nuclei, enhanced osteoclast bone resorption, and promoted MMP-9 protein expression in a concentration-dependent manner. These findings indicate that 1alpha,25-(OH)2D3 administered at a physiological relevant concentration promoted osteoclast formation and could regulate osteoclast bone metabolism by increasing MMP-9 protein expression during osteoclast differentiation.
Acid Phosphatase/metabolism ; Animals ; Blotting, Western ; Calcitriol/*pharmacology ; Calcium Channel Agonists/pharmacology ; *Cell Differentiation ; Cell Line ; Cell Proliferation ; Gene Expression Regulation, Enzymologic/*drug effects ; Isoenzymes/metabolism ; Matrix Metalloproteinase 9/*genetics/metabolism ; Mice ; Osteoclasts/*cytology/*enzymology ; Tetrazolium Salts ; Thiazoles

OBJECTIVETo investigate the beneficial effects of Rhein (RH) on hepatic progression in hepatitis B virus (HBV)-transgenic mice with nonalcoholic steatohepatitis induced by a high-fat (HF) diet.

METHODSA mice model of HBV chronic infection concomitant with liver steatosis was induced by a HF diet in 4-week old HBV-transgenic mice for 16 weeks (n = 130). Thereafter, the mice were divided randomly into control group (back to normal chow), model group (continuing HF diet), RH group [continuing HF diet and administering with 120 mg/(kg x d) RH by gavage] and Essentiale group [continuing HF diet and administering with 69.2 mg/(kg x d) Essentiale by gavage] with 30 mice in each, and were sacrificed at the end of 24-week and 48-week respectively. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG) and fasting plasma glucose (FPG) were measured by an automatic biochemical analyzer, and serum HBV-DNA was determined with qPCR. Hepatic histology was evaluated by HE staining with a light microscope.

RESULTS(1) An histological change composed of steatosis, lymphocytes intralobular infiltration and ballooning was observed after 48 weeks feeding of HF diet, in part mimicking that of NASH patients as evidenced by a NAFLD activity score (NAS) of 3.58 +/- 1.44 points. (2) Histologically, the NAS of model group was higher than that of control group at both time points. RH failed to lessen NAS whereas Essentiale improved the NAS at 48-week. (3) Serum levels of TC, TG and FPG were significantly different between 4 groups at 24-week, with a comparable low value in both RH and Essentiale group. A similar change was evident at 48-week. (4) In terms of HBV viral load, a significantly lower level in Essentiale group than the others was observed at both time points.

CONCLUSIONHF diet feeding is able to induce a mouse model of HBV chronic infection concomitant with NASH. RH is effective in alleviating the glucose and lipid metabolism but ineffective in improving the hepatic histology in this model, in contrast, backing to normal chow achieved a better effect in this aspect.

Animals ; Anthraquinones ; administration & dosage ; Diet, High-Fat ; adverse effects ; Disease Models, Animal ; Disease Progression ; Fatty Liver ; complications ; etiology ; metabolism ; prevention & control ; Female ; Glucose ; metabolism ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; complications ; metabolism ; virology ; Humans ; Lipid Metabolism ; drug effects ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Non-alcoholic Fatty Liver Disease

OBJECTIVEThis study was designed to examine the in vitro effects of fenvalerate on steroid production and steroidogenic enzymes mRNA expression level in rat granulosa cells.

METHODSUsing primary cultured rat granulosa cells (rGCs) as model, fenvalerate of various concentrations (0, 1, 5, 25, 125, 625 micromol/L) was added to the medium for 24 h. In some cases, optimal concentrations of 22(R)-hydroxycholesterol (25 micromol/L), Follicle stimulating hormone (FSH, 2 mg/L), or 8-Bromo-cAMP (1 mmol/L) were provided. Concentrations of 17 beta-estradiol(E2) and progesterone (P4) in the medium from the same culture wells were measured by RIA and the steroidogenic enzyme mRNA level was quantified by semi-quantitative RT-PCR.

RESULTSFenvalerate decreased both P4 and E2 production in a dose-dependent manner while it could significantly stimulate rGCs proliferation. This inhibition was stronger in the presence of FSH. Furthermore, it could not be reversed by 22(R)-hydroxycholesterol or 8-Bromo-cAMP. RT-PCR revealed that fenvalerate had no significant effect on 3 beta-HSD, but could increase the P450scc mRNA level. In addition, 17 beta-HSD mRNA level was dramatically reduced with the increase of fenvalerate dose after 24 h treatment.

CONCLUSIONFenvalerate inhibits both P4 and E2 production in rGCs. These results support the view that fenvalerate is considered as a kind of endocrine-disrupting chemicals. The mechanism of its disruption may involve the effects on steroidogenesis signaling cascades and/or steroidogenic enzyme's activity.

3-Hydroxysteroid Dehydrogenases ; analysis ; metabolism ; 8-Bromo Cyclic Adenosine Monophosphate ; pharmacology ; Animals ; Base Sequence ; Cells, Cultured ; Dose-Response Relationship, Drug ; Estradiol ; analysis ; metabolism ; Female ; Follicle Stimulating Hormone ; pharmacology ; Granulosa Cells ; cytology ; drug effects ; metabolism ; Hydroxycholesterols ; pharmacology ; Nitriles ; pharmacology ; Progesterone ; analysis ; metabolism ; Pyrethrins ; pharmacology ; RNA, Messenger ; analysis ; metabolism ; Rats ; Steroids ; metabolism

OBJECTIVETo explore the effect of extracellular signal regulated kinase 1/2 (ERK1/2) on edaravone (EDA)-triggered protection against myocardial toxicity induced by isoprenaline (ISO) in H9c2 myocardial cells (H9c2 cells).

METHODSH9c2 cells were exposed to ISO at different concentrations to establish a cardiac toxicity model induced by persistent excitation of β1 receptor. EDA was added before ISO as a pretreatment. PD-98059, an ERK1/2 inhibitor, was administered 1 h prior to EDA to inhibit the phosphorylation of ERK1/2. Cell viability was measured using cell counter kit (CCK-8). The expressions of p-ERK1/2 and t-ERK1/2 were tested by Western blotting. Mitochondrial membrane potential (MMP) was detected by Rhodamine123 (Rh123) staining and photofluorography.

RESULTSExposure of H9c2 cells to 80 µmol/L ISO for 24 h down-regulated ERK1/2 phosphorylation and repressed MMP. Pretreatment with 10-40 µmol/L EDA for 1 h inhibited ISO-induced myocardial toxicity and pretreatment of 40 µmol/L EDA partially rescued ERK1/2 phosphorylation and MMP level. PD-98059 abolished cardiac protection of EDA, leading to myocardial toxicity and MMP loss.

CONCLUSIONEDA can protect H9c2 cells against myocardial injury induced by ISO by suppressing ISO-triggered inhibition of ERK1/2 activation.

Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Cell Line ; Flavonoids ; pharmacology ; Isoproterenol ; toxicity ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; Phosphorylation ; Rats

OBJECTIVETo extract and identify semen-derived exosome using PEG6000.

METHODSExosomes were extracted from semen specimens from 6 healthy volunteers with step-by-step centrifugations and ultracentrifugation prior to 8% PEG6000 enrichment. The extracted exosomes were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blotting.

RESULTSThe pellets obtained were round or elliptic membrane vesicles 30 to 150 nm in diameter with intact double membranes and contained low electron density material. The pellets expressed CD63, ALIX and TSG101 molecules but not calnexin that was expressed in sperm cells.

CONCLUSIONThe PEG6000-based method for extraction of exosomes from semen samples facilitates future studies of seminal exosomes.

BACKGROUNDThe chronic pathological changes in vascular walls of hypertension may exert destructive effects on multiple organ systems. Accumulating evidence indicates that inflammatory reactions are involved in the pathological changes of hypertension. Three peroxisome proliferator-activated receptors (PPARs) have been identified: PPARalpha, PPARbeta/delta, and PPARgamma, all of which have multiple biological effects, especially the inhibition of inflammation. The aim of this study was to evaluate PPAR isoforms expression profile in important organs of spontaneously hypertensive rats (SHR) and to understand the modulation of endogenous PPAR isoforms under inflammatory condition.

METHODSTissues (kidney, liver, heart, and brain) were dissected from SHR and age-matched control Wistar-Kyoto rats (WKY) to investigate the abundance of PPAR isoforms and PPAR-responsive genes (acyl-CoA oxidase and CD36). The expression of CCAAT/enhancer-binding protein delta (C/EBPdelta), which can trans-activate PPARgamma expression, was also observed. The inflammatory response was analyzed by the expression of inflammatory mediators inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, interleukin-1 beta (IL-1beta), and tumor necrosis factor alpha (TNFalpha), and formation of carbonyl and nitrated proteins.

RESULTSThe expressions of 3 PPAR isoforms and PPAR-responsive genes were markedly upregulated in SHR compared with those of WKY. Specifically, the expression of PPARalpha protein in the kidney, liver, heart and brain increased by 130.76%, 91.48%, 306.24%, and 90.70%; PPARbeta/delta upregulated by 109.34%, 161.98%, 137.04%, and 131.66%; PPARgamma increased by 393.76%, 193.17%, 559.29%, and 591.18%. In consistent with the changes in PPARgamma, the expression of C/EBPdelta was also dramatically elevated in SHR. Inflammatory mediators expressions were significantly increased in the most organs of SHR than WKY. As a consequence, increased formation of carbonyl and nitrated proteins were also observed in the most organs of SHR.

CONCLUSIONSThese findings suggest an enhanced inflammatory response in the organs of SHR, which might play a key role in pathogenesis of hypertension and secondary organ complications. Changes (increases) in PPARs expression may reflect a compensatory mechanism to the inflammatory status of hypertensive rats.

Animals ; Blood Pressure ; Blotting, Western ; E-Selectin ; genetics ; metabolism ; Gene Expression ; Hypertension ; genetics ; metabolism ; physiopathology ; Inflammation ; genetics ; metabolism ; physiopathology ; Interleukin-1beta ; genetics ; metabolism ; Male ; PPAR alpha ; genetics ; metabolism ; PPAR delta ; genetics ; metabolism ; PPAR gamma ; genetics ; metabolism ; Peroxisome Proliferator-Activated Receptors ; genetics ; metabolism ; Plethysmography ; methods ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

OBJECTIVETo evaluate head and neck cancer and surgical treatment impact the quality of life (QOL).

METHODSIn this study, 49 cases of head and neck cancer patients were recruited. Among them, 27 cases were laryngeal cancer, 14 cases were tongue cancer and 8 patients were recurrence of nasal pharyngeal cancer after radical radiotherapy. To demonstrate the cancer in different sites of the head and neck impact QOL of the patients in a different way and cancer impact QOL on the physical well-being, social family well-being, emotional well-being, functional well-being of the patients and quality of life (QOL) changed in different time-point before and after operation, QOL was assessed before surgical treatment and at 1,6 months after operation by means of a performance status scale for head and neck cancer patients (PSS-HN) and the functional assessment of cancer therapy head and neck (FACT-H&N) questionnaire.

RESULTSQOL deteriorated significantly in head and neck cancer patients. Cancer in different sites impact on QOL differently especially in patients with tongue cancer (PSS-HN P = 0.0361, FACT-H&N P = 0.0487). Head and neck cancer impact QOL on the physical well-being, social family well-being, emotional well-being, functional well-being of the patients in FACT-H&N questionnaire especially for emotional well-being domains (F = 2.78, P = 0.0311). The QOL in patients deteriorated by surgical treatment and it could be improved following the time. At the 6 months after operation it nearly reached the same scores that assessed before the operation (PSS-HN t = 2.03, P = 0.1120 FACT-H&N t = 1.03, P = 0.1180). Different surgical approaches and different reconstruction methods have different impact on QOL for patients. Laryngeal cancer patients with partial laryngectomy were 107.20 in FACT-H&N while total laryngectomees were 97. 71 at the 6 months after operation, with statistically difference (t = 3.02, P = 0.0430). Tongue cancer patients without reconstruction were 119. 24 in FACT-H&N while the others with reconstruction were 111.39 at the 6 months after operation (t = 3.00, P = 0.0472).

CONCLUSIONSThe QOL in head and neck cancer patients can be assessed by the questionnaire and it can be improved by selecting treatment regimen, surgical approaches and reconstructive methods.

Adult ; Aged ; Female ; Head and Neck Neoplasms ; surgery ; Humans ; Laryngeal Neoplasms ; surgery ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; surgery ; Quality of Life ; Surveys and Questionnaires ; Tongue Neoplasms ; surgery