The Long Chain Acyl-coenzyme A Synthetase Family and Malignant Tumors / 中国生物化学与分子生物学报

Disorders of the fatty acid metabolism can lead to cancer. The long chain acyl-coenzyme A synthetase (ACSL) family is important in fatty acid metabolism and is responsible for activating long chain fatty acids. In cancer cells, the regulatory effect of ACSLs is often disrupted, and the distribution, type, and quantity of fatty acids are altered. These alterations can lead to cancer development and other metabolic diseases. ACSLs include five subtypes in mammals, namely ACSL1, 3, 4, 5, and 6. ACSL1 is important in the synthesis and distribution of triglycerides. ACSL3 contributes to the formation of lipid droplets, which are important for maintaining lipid homeostasis. The expression of ACSL4 is related to steroid hormones and plays an important role in ferroptosis. ACSL5 can catalyze the metabolism of exogenous fatty acids but not the metabolism of de novo fatty acids. ACSL6 is important in fatty acid metabolism in the brain, spermatogenesis, and ovary. The regulatory factors of ACSLs include transcription factors, coactivators, hormone receptors, protein kinases, and small non-coding RNAs. These factors regulate mitochondria-mediated energy metabolism, endoplasmic reticulum stress, and the tumor inflammatory microenvironment through fatty acid metabolism. In addition, ACSLs serve as independent prognostic factors, biomarkers for clinical diagnosis, and therapeutic targets for various cancers. In recent years, accumulating evidence has demonstrated the important roles of ACSLs in the occurrence and development of cancer. This article focuses on the ACSL family, the relationship between ACSL and malignant tumors, and tumor therapies based on lipid metabolism by ACSLs. The information provides a theoretical basis for the further study of the ACSL family as molecular candidates for the targeted therapy of tumors.

Effect of Isoalantolactone on Apoptosis in MCF-7 Cells Via Mitochondrial and Phosphatidylinositol 3-Kinase /Akt Signaling Pathways / 中国药学杂志

OBJECTIVE: To study the effect of isoalantolactone on inhibiting proliferation of MCF-7 and induce apoptosis in vitro and further to explore its machinism via mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways. METHODS: The subject investigated isoalantolactone in MCF-7 cells proliferation inhibition by MTT and SRB methods, and matching the results of two methods; observing morphological changes by inverted microscope and each phase of apoptosis of MCF-7 cells effected by isoalantolactone after 24 h with Hoechst 33258 staining method. Using transmission electron microscopy to observe MCF-7 cells morphology change to determine the mechanism of research; rhodamine 123 tag, laser confocal scanning microscope detection isoalantolactone on the effect of MCF-7 cells mitochondrial membrane potential; Using Western blot to the expression of Bcl-2, Bax, Akt and p-Akt; detecting caspase-3 activity in MCF-7 cells by colorimetry method. RESULTS: Isoalantolactone has strong inhibition of proliferation in MCF-7 cells, IC50 values of MTT and SRB methods were 15.21 and 14.908 μg•mL-1, and in a dose -dependent manner; the morphological of MCF-7 cells was changed after the treatment by Hoechst staining method; morphological changes were observed under transmission electron microscopy of cells display, the drug group cells showed typical apoptotic characteristics of different periods. With the concentrations of isoalantolactone increasing, the level of mitochondrial membrane potential reduced. Western blot result showed that, isoalantolactone could down regulate the expression of anti apoptotic protein Bcl-2, p-Akt, and up regulate the expression of pro-apoptotic protein Bax, had no effect on the expression of Akt protein. And the activity of caspase-3 could be raised by increasing dosage, compared with the control group with significant difference(P < 0.01). CONCLUSION: Isoalantolactone effectively inhibites the proliferation of MCF-7 cells through mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways, which is regulated by activation of caspase-3, down-regulation of Bcl-2, and up-regulation of Bax. Isoalantolactone-induced apoptosis is involved in mitochondrial and the PI3K/Akt pathway.

Xanthotoxin induces apoptosis in SGC-7901 cells through death receptor pathway / 中草药·英文版

Objective: To investigate the effects of xanthotoxin from Apiaceae medicinal plants on cell proliferation and apoptosis, and explore its mechanism of action against human gastric carcinoma SGC-7901 cells in vitro. Methods: SGC-7901, HepG-2, MCF-7, and A549 cells were treated with different concentrations of xanthotoxin (10, 20, 60, 80, 100, 120, 140, and 160 µg/mL) for 48 h, and the cell viability (IC50) was determined by MTT assay; Xanthotoxin-induced apoptosis in cells was observed by using Hoechst 33258 Staining Kit and Annexin V-FITC Apoptosis Detection Kit; Flow cytometry was used to detect apoptosis related proteins of Fas/FasL, Bid, and DR5/TRAIL proteins in human gastric carcinoma SGC-7901 cells after being treated by xanthotoxin; The influence of xanthotoxin on Caspase-8 protein expression in the cells was determined by Flouormetric Assay Kit. Results: Xanthotoxin obviously inhibited SGC-7901, HepG-2, MCF-7, and A549 cells proliferation, and its inhibition was in a concentration-dependent manner; flow cytometry results showed that in a certain concentration range, xanthotoxin can increase the expression levels of Fas/FasL and DR5/TRAIL proteins in a concentration-dependence manner. The content of Bid protein in cells was increased, and it showed concentration-dependence. Conclusion: Xanthotoxin may induce SGC-7901 cells apoptosis in a certain concentration range through the Fas/FasL protein mediated death receptor pathway, or by DR5/TRAIL mediated death receptor pathway, and increase the expression level of death receptor protein, activation Caspase-8, activating downstream effect factor, inducing cell apoptosis, or activate Caspase-8 cutting activate protein Bid, and then enter the mitochondrial pathway, induction of apoptosis.

Effect of p54nrb gene silencing on the endothelial cells migration of human umbilical vein and the angiogenesis in vitro / 解放军医学杂志

Objective To explore the effects of p54nrb gene silencing on the proliferation, migration of human umbilical vein endothelial cell (HUVEC) and angiogenesis in vitro. Methods HUVECs were infected by p54nrb-specific shRNA-containing lentiviruses for 24h, then the cells were cultured in media containing puromycin until stable establishment of p54nrb-silencing HUVEC cell line. The efficiency of p54nrb gene silencing technique was determined by Western blotting, and the effects of this technique on the proliferation of HUVECs was assessed by the Cell Counting Kit-8 (CCK-8) assay. The migration of p54nrbsilencing HUVECs was measured by wound healing assay and Transwell motility assay. Vessel formation assay was used to detect the angiogenesis ability of p54nrb-silencing HUVECs. Results Western blotting showed that the expression of p54nrb protein in p54nrb-silencing HUVECs decreased significantly, implying a stable establishment of p54nrb-silencing HUVEC cell line. The CCK-8 assay revealed that knockdown of p54nrb gene promoted the proliferation of HUVECs slightly. Wound healing assay and Transwell motility assay displayed that knockdown of p54nrb significantly inhibited the motility of HUVECs. Vessel formation assay showed that knockdown of p54nrb inhibited in vitro the formation of vessel-like structures of HUVEC cells. Conclusion p54nrb significantly promote the migration and angiogenesis in vitro of HUVECs, and may be an important modulin involved in angiogenesis.

Pharmacological activity of Terminalia chebula / 中国中药杂志

Terminalia chebula Retz, known as the "king" of Mongolian and Tibetan medicines, is a drug for a wide range of diseases. The main chemical components of myrobalan include triterpene acid, galloyl glucose, anthraquinonoid. The modern pharmacological studies show that myrobalan has multiple biological activities, including antimicrobial, anti-inflammatory, antioxidation as well as anti-tumor. Based on domestic and foreign literatures in recent years, this paper gave a review on the advance of studies for pharmacological activity of T. chebula. and its active components, so as to provide a reference for the in-depth studies on the pharmacological action of myrobalan, and the further development and utilization of myrobalan.

Obstructive Sleep Apnea Syndrome is Associated with Metabolic Syndrome among Adolescents and Youth in Beijing: data from Beijing Child and Adolescent Metabolic Syndrome Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Obstructive sleep apnea (OSA) syndrome has a negative impact on the health of millions of adolescents and youth. The aim of this study was to evaluate the associations of OSA syndrome with obesity and cardiometabolic risk factors among adolescents and youth at risk for metabolic syndrome (MS).</p><p><b>METHODS</b>A total of 558 subjects aged 14-28 years were recruited from the Beijing Child and Adolescent Metabolic Syndrome Study. Each underwent a 2-h oral glucose tolerance test (OGTT), echocardiography, and liver ultrasonography. Anthropometric measures, blood levels of glucose, lipids, and liver enzymes were assessed. Subjects with high or low risk for OSA were identified by Berlin Questionnaire (BQ).</p><p><b>RESULTS</b>Among the subjects in obesity, 33.7% of whom were likely to have OSA by BQ. Subjects with high risk for OSA had higher neck and waist circumference and fat mass percentage compared to those with low risk for OSA (P < 0.001). Moreover, significant differences in levels of lipids, glucose after OGTT, and liver enzymes, as well as echocardiographic parameters were found between the two groups with high or low risk for OSA (P < 0.05). The rates of nonalcoholic fatty liver disease (71.0% vs. 24.2%), MS (38.9% vs. 7.0%), and its components in high-risk group were significantly higher than in low-risk group.</p><p><b>CONCLUSIONS</b>The prevalence of OSA by BQ was high in obese adolescents and youth. A high risk for OSA indicates a high cardiometabolic risk. Mechanisms mediating the observed associations require further investigation.</p>

Microbubbles targeted to P-selectin for evaluating testicular ischemia-reperfusion injury in rabbits / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the feasibility of evaluating complete ischemia-reperfusion injury (IRI) of the testis by contrast-enhanced ultrasonography with microbubbles (MB) targeted to P-selectin (MBp) in rabbits.</p><p><b>METHODS</b>We randomly divided 30 healthy adult rabbits into five groups of equal number (control, 0.5 h IRI, 1 h IRI, 2 h IRI, and 4 h IRI), prepared phospholipid MB and MBp, and performed contrast-enhanced ultrasonography of the bilateral testes with MB or MBp at an interval of 20 min at different times after IRI. When MB or MBp disappeared completely in the healthy testis at 4 to 5 min after intravenous injection, we recorded the power of the first frame (F-P) in the IRI testes followed by immunohistochemical staining of the testis tissue.</p><p><b>RESULTS</b>CEU with MBp achieved a significantly higher F-P than that with MB in all the IRI groups (P < 0.05), which was (8.34 +/- 1.20) versus (1.87 +/- 0.25) 10(-5) AU at 2 hours, but there was no significant difference between MB and MBp in the control rabbits (0 AU, P > 0.05). Immunohistochemistry showed a significantly time-dependent increase in the expression of P-selectin in the vascular endothelial cells of the IRI testes, but not in those of the control.</p><p><b>CONCLUSION</b>Contrast-enhanced ultrasonography with MBp can be used to evaluate the inflammatory reaction of testicular ischemia-reperfusion injury.</p>

Effect of interstitial chemotherapy with ricin temperature-responsive gel for anti-breast cancer and immune regulation in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effect of ricin temperature response gel on breast cancer and its regulatory effect on immune function in rats.</p><p><b>METHODS</b>Ricin was purified by chromatography and identified by immunoblotting. The rat subcutaneously transplanted breast cancer model was established. Forty model rats with a tumor diameter of about 3.0 cm were subjected to the study. They were randomized into four groups equally: the model group and three treated groups (blank gel, ricin, ricin-gel) were administered with blank gel, ricin, and ricin temperature response gel via percutaneous intratumor injection, respectively. The tumor was isolated 10 days later for the estimation of tumor inhibition rate (TIR) by weighing, pathologic examination, and detection of tumor apoptosis-associated genes bcl-2 and bax with semiquantitative RT-PCR. Also, peripheral blood was obtained to test T-lymphocyte subsets, the killing function of lymphocytes, and the contents of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2). The outcomes were compared between groups.</p><p><b>RESULTS</b>The TIR in the ricin-gel group was 61.8%, with the pathologic examination showing extensive tumor tissue necrosis. Compared with the model group, after ricin temperature response gel treatment, bcl-2 expression was down-regulated, bax expression was up-regulated, CD4+ lymphocytes and CD4+/CD8+ ratio in peripheral blood were increased, the killing function of lymphocytes was enhanced, and the contents of TNF-α and IL-2 were elevated (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Intratumor injection of ricin temperature-responsive gel showed significant antitumor effect on breast cancer and could enhance the immune function in the tumor-bearing rat.</p>

Relationship between metabolic syndrome and adipokines on diabetes among high-risk populations / 中华流行病学杂志

Objective To study the relationship between adipokines and metabolic syndrome (MS),and the predictive value of adipokines on diagnosis of MS.Methods According to the IDF consensus worldwide definition on MS in 2005,we divided the subjects into 4 groups:115 in MS0 (with none of MS component) ; 118 in MS1 (with one MS component) ; 77 in MS2 (with two MS components) and 104 in MS3 (with none of MS component).Serum levels of leptin,visfatin adiponectin and resistin were measured in these groups,using the enzymelinked immunosorbent assay (ELISA) method.Retinol-binding protein 4 (RBP-4) was assessed by radioimmtmoassay (RIA).Result ( 1 ) Serum adiponectin level decreased while the serum level of leptin and RBP-4 increased in women with the number of MS components gathered.However,the level of visfatin obviously decreased only in the MS3 phase.The level of resistin showed no changes with MS components gathered.(2) Detection rates of the MS components such as high blood pressure,hyperglycemia,dyslipidemia,insulin resistance and obesity were significantly higher in the Q4 group with high level of leptin when compared to the Q1 group with lower level (odd ratio:Q4/Q1 is 1.3,1.8,1.6,5.2,3.0respectively).(3) The higher level of serum RBP-4 was not only associated with greater risk for impaired glucose regulation (odd ratio:Q4/Q1=2.6),but also significantly with the risks for hyperglycemia ( odd ratio:Q4/Q 1 =1.6 ) dyslipidemia ( odd ratio:Q4/Q 1 =1.9 ),obesity ( odd ratio:Q4/Q 1 =1.5 ) and MS (odd ratio:Q4/Q 1 =2.7).In the Q4 group with higher levels of RBP-4,the positive rates of MS reached 50％.(4) The detection rates of MS components such as dyslipidemia,obesity,hyperglycemia,and insulin resistance were significantly higher in the Q1 group with the lowest level of adiponeptin when compared to the Q4 group with the highest level.Conclusion The levels of adipokines,serum adiponectin,leptin and RBP-4 showed significant associations with MS.Our findings suggested that these adipokines might serve as the key factors that participating in MS and could be used as markers for early prediction of MS as well as the new targets for therapy.

Interaction between smoking and obstructive sleep apnea: not just participants / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the current evidence that links smoking to obstructive sleep apnea (OSA) and to discuss some potential mechanisms proposed for these links.</p><p><b>DATA SOURCES</b>We searched PubMed and Medline to identify studies investigating the interaction between smoking and OSA.</p><p><b>STUDY SELECTION</b>Articles regarding the relationship between smoking and OSA were selected. Studies considered smoking as a confounding factor were excluded.</p><p><b>RESULTS</b>The association of smoking and OSA has been confirmed in several studies. The effects of smoking on the pathophysiology of OSA may include smoking-induced upper airway inflammation, stimulant effects of nicotine on upper airway muscles, and a "rebound effect" due to nightly short-term nicotine withdrawal, or all of the above. In addition, the coexistence of OSA and smoking may have more widespread implications for cardiovascular dysfunction in patients with OSA. Finally, OSA might be responsible for the addiction to nicotine.</p><p><b>CONCLUSIONS</b>Smoking may act as a risk factor for OSA and join with OSA in a common pathway to increase the risk of systematic injury. OSA, in turn, may be a predisposing factor for smoking. Thus, smoking cessation is recommended when considering treatment for OSA, and treating OSA may be a necessary precondition for successful smoking cessation.</p>

Association between both resistin, visfatin and insulin resistance as well as β cell function in the first-degree relatives of type 2 diabetes mellitus / 中华流行病学杂志

Objective To study the association between the levels of scrum resistin, visfatin and insulin resistance as well as β-cell dysfunction in the first-degree relatives (FDR) of type 2 diabetes mellitus (T2DM), and to investigate the role of these adipocytokins in pathogenesis of T2DM. Methods Serum levels of resistin, visfatin as well as fasting true insulin (FTI), proinsulin (FPI) levels were measured in 71 patients with newly diagnosed T2DM. 55 subjects with IGT/IFG and 174 NGT from first-degree relatives of T2DM, and 114 subjects of NGT without T2DM family history served as control group (NC). Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR) and β-cell function was evaluated by HOMA-β and fasting PI-to-TI ratio (FPI/TI). Lipid profile, liver function and kidney function were also tested. Anthropometrical parameters such as body mass index (BMI), waist circmference and blood pressure were also recorded and life style and food intake spectrum investigated. Results (1)There were no significant differences of serum resistin levels among the four groups (P ＞ 0.05 ). The serum resistin level was not correlated with HomA-IR, HomA-β and obesity markers (P＞0.05). (2) The serum visfatin levels of DM group, IGT/IFG and NGT group were lower than the NC group (P＜0.05). There were no significant difference among DM group, IGT/IFG group and NGT. The serum visfatin level was not correlated with HOMA-IR and obesity markers (P＞0.05) , but negatively correlated with fasting blood glucose, 2 h postprandial blood glucose and blood pressure (P＜0.05). Conclusion The adipokine profile in FDRs of T2DM had distinctively altered before the development of impaired glucose tolerance. Serum levels of visfatin, showed a favorable effect on glucose metabolism also had a significant decrease on serum levels in the early stage of T2DM.

Studies of betuionic acid on cell cycle and related protein expressions on mice of bearing H22 tumor cells / 中国中药杂志

<p><b>OBJECTIVE</b>To study the betulonic acid on the cell cycle and related protein expressions on mice of bearing H22 tumor cells.</p><p><b>METHOD</b>Flow cytometray was used to observe the changes of betulonic acid on the cell cycle and P53 of H22 tumor cells. Immunohistochemistry was determined the espressions of PI3K and AKT.</p><p><b>RESULT</b>Increasing the doses of betulonic acid, the number of H22 cells in S phase and G2 phase was increasing gradually, it can speculate that when the betulonic acid act on cells, the cells were blocked in S and G2 phase and inhibited the protein expressions of PI3K and AKT.</p><p><b>CONCLUSION</b>Betulonic acid may be up-regulate the activity of P53 and inhibite the expressions of PI3K and AKT, so that it inhibited the survival pathway of tumor cells.</p>

Cohort studies on cancer mortality of digestive system among workers exposed to asbestos: a meta-analysis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To determine if there are excessive risks of malignant tumors or not among workers exposed to asbestos by applying a meta-analysis technique.</p><p><b>METHODS</b>All data meeting the criteria of cohort studies on cancer mortality of digestive system among workers exposed to asbestos would be incorporated into the meta-analysis. The pooled standardized mortality ratios (SMR) and their corresponding 95% confidence intervals (CIs) for main cancer sites of digestive system were calculated by using two approaches of un-weighted ratio and random effects model. The heterogeneity and its sources of the results were examined with a Q-statistic and Z-score test.</p><p><b>RESULTS</b>69 asbestos-exposed cohorts were summarized. The significantly elevated meta-SMR for all deaths (1.16), all cancers (1.42), cancer of digestive system (1.15) and cancer of stomach (1.20) among workers exposed to chrysotile alone or mixed asbestos were observed (P < 0.01). The stomach cancer SMR was significantly increased in the asbestos cement workers, the screening mine workers and the insulators, (1.27, 1.21 and 2.13 respectively) (P < 0.05). meta-SMR for cancers at other sites of digestive system including esophagus, colon, rectum and liver were not significant.</p><p><b>CONCLUSION</b>There are likely excessive risks of cancer of stomach among workers exposed to asbestos. However, there is likely no convincing indication of an etiological association between asbestos exposure and cancers at other sites of digestive system.</p>

Influence of glutamate and NMDA-receptor antagonist MK-801 on the electric activities of pain-excitation neurons in the nucleus accumbens of rats / 生理学报

The experiment explored the influence of glutamic acid (Glu) and the NMDA-receptor antagonist dizocilpine maleate (MK-801) on the pain-evoked responses of pain-excitation neurons (PEN) in the nucleus accumbens (NAc) of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The discharges of PEN in NAc were recorded by glass microelectrode. We observed the influence of intracerebroventricular (icv) injection of Glu and microinjection of MK-801 into the NAc on the noxious stimulation-evoked activities of PEN in NAc. The results showed that the noxious stimulation potentiated the electric activities of PEN in NAc. Intracerebroventricular injection of Glu (10 nmol/10 microl) increased the frequency of the discharge of PEN evoked by the noxious stimulation in NAc, the Glu-induced response was blocked by the injection of MK-801 (1.0 nmol/0.5 microl) into NAc. MK-801 partly inhibited the response of PEN upon the noxious stimulation. It is therefore suggested that the facilitatory effect of Glu on PEN response in NAc to the noxious stimulation is mediated by NMDA receptors, and that Glu and NMDA receptors are involved in the modulation of nociceptive information transmission in the NAc.

Multicenter controlled study on transient asthma-stopping action of acupuncture at "Qingchuan point" / 中国针灸

<p><b>OBJECTIVE</b>To test and verify the transient therapeutic effect of acupuncture at point "Qingchuan" on bronchial asthma.</p><p><b>METHODS</b>Two hundred cases of bronchial asthma at acute attack stage were divided into a trial group of 100 cases treated with acupuncture at point "Qingchuan" and a control group of 100 cases treated with acupuncture at Dingchuan (EX-B1).</p><p><b>RESULTS</b>The total effective rate was 92.60% and the effect occurred within 42-860 seconds after acupuncture in the trial group, and 81.0% and within 114-126 seconds in the control group, respectively, with very significant differences between the two groups (P < 0.01, P < 0.001).</p><p><b>CONCLUSION</b>Acupuncture at point "Qingchuan" can significantly improve asthmatic state in the patient of bronchial asthma with action of rapidly stopping asthma.</p>

Influence of sargassum fusiforme polysaccharide on apoptosis of tumor cells / 中国中药杂志

<p><b>OBJECTIVE</b>To study mechanism of antitumor activity of Sargassum Fusiforme Polysaccharide (SFPS).</p><p><b>METHOD</b>The effect on cell cycle and apoptosis was studied with flow cytometry (FCM). Intracellular calcium concentration [Ca2+]i was marked with Fluo-3/AM and measured with laser scanner confocal microscope (LSCM).</p><p><b>RESULT</b>SFPS inhibited G0/G1 stage SGC-7901 from entering to S stage and increased APO%. The [Ca2+]i showed a transient rise and return to the original level. The concentration could be raised again by administering CaCl2.</p><p><b>CONCLUSION</b>The antitumor effect of SFPS seems to be accomplished through the apoptosis associated with the increase in intracellular calcium concentration. Intracellular stores release the calcium during its action.</p>