1.Hypothermia combined with dexamethasone reduces ICAM1 expression and protects spermatogenesis after testicular torsion-detorsion.
Hui-Chang LI ; Wu-Bin WENG ; Chang-Ming LIU ; Ben-Jiang QIAN ; Miao-Chun LIN
National Journal of Andrology 2014;20(7):618-623
OBJECTIVETo investigate the protective effect of hypothermia combined with dexamethasone on spermatogenesis and the expression of intercellular adhesion molecule 1 (ICAM1) after testicular torsion-detorsion.
METHODSWe made unilateral testicular torsion models in 100 pubertal male Sprague-Dawley rats by 720 degree torsion of the left testis and then randomly divided them into four groups of equal number to be treated with normal temperature + physiological saline (group A), hypothermia + physiological saline (group B), normal temperature + dexamethasone (group C), and hypothermia + dexamethasone (group D). After 48 hours, we collected the testes, observed pathological changes of the testicular tissue by HE staining under the light microscope, detected the apoptosis of spermatogenic cells by TUNEL, and determined the expression of ICAM1 by Western blot.
RESULTSHE staining showed different degrees of testicular tissue injury in the four groups of rats, most obvious in group A, but mild in the other three. The ICAM1 protein expression was significantly higher in group A (0.68 +/-0. 03) than in B (0. 49 +/- 0. 06, P <0. 05) , C (0. 46 +/- 0. 09, P < 0.05) , and D (0.17 +/- 0.08, P <0.01). The nuclei were deep brown or brown. Lots of apoptotic spermatogenic cells were seen in the torsion testis of group A, with a significantly higher apoptosis index ( [33. 13 +/- 3.21 ]%) than in B ( [ 17. 12 +/-5.23 ]%, P < 0.05), C ([14.13 +/- 2.03]%, P <0.05), and D ([9.05 +/- 1.03]%, P <0.01).
CONCLUSIONHypothermia combined with dexamethasone can protect the testis from injury as well as the reproductive function of the testis after testicular torsion-detorsion and reduce the expression of ICAM1.
Animals ; Dexamethasone ; pharmacology ; Disease Models, Animal ; Hypothermia, Induced ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Spermatic Cord Torsion ; metabolism ; physiopathology ; Spermatogenesis ; drug effects
2.Advances on Keap1-Nrf2 protein-protein interaction inhibitors and degraders
Jian-yu YAN ; Guo-dong LIU ; Zhen-yuan MIAO ; Chun-lin ZHUANG
Acta Pharmaceutica Sinica 2022;57(10):2932-2948
Oxidative stress is a redox imbalance in the body, which is one of the important factors leading to tissue damage and diseases. The nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) signaling pathway is not only an important defense system against oxidative damage, but also one of the key signaling pathways of the antioxidant capacity. Numerous studies have shown that targeting the Keap1-Nrf2 signaling pathway to activate Nrf2 has become an effective strategy for the treatment of oxidative stress and related diseases. Using small molecules to directly block the Keap1-Nrf2 protein-protein interaction (PPI) is one of the important directions for activating Nrf2 and exerting the cytoprotective effect, which can avoid the potential side effects of covalent modification of Nrf2. On the other hand, the Keap1 is an efficient E3 ubiquitin ligase that has been used in the design of proteolysis targeting chimeras (PROTACs). This review summarizes the research progresses of Keap1-Nrf2 protein interaction inhibitors and degraders based on the Keap1 E3 ubiquitination system in recent years.
3.Crypotanshione reduces the expression of metadherin in DU145 prostate cancer cells.
Yi YAO ; Hui-zhang LI ; Ben-jiang QIAN ; Chang-ming LIU ; Jia-bin ZHANG ; Miao-chun LIN
National Journal of Andrology 2015;21(9):782-787
OBJECTIVETo investigate the effects of crypotanshinone (CPT) on the proliferation and apoptosis of DU145 prostate cancer cells as well as on the metadherin expression and the downstream PI3K/AKT signaling pathway in the DU145 cells.
METHODSWe treated DU145 prostate cancer cells with different concentrations of CPT for 24, 48, and 72 hours followed by evaluation of the proliferation and apoptosis of the cells by MTT assay and TUNEL, respectively. We determined the expressions of metadherin protein and mRNA in the DU145 cells by Western blot and RT-PCR respectively at different time points after CPT treatment. We also detected the expressions of the proteins metadherin, AKT, p-AKT, and Bcl-2 in the CPT-treated DU145 cells at 48 hours.
RESULTSCPT significantly inhibited the proliferation of the DU145 cells in a dose- and time-dependent manner (P < 0.05). After treatment with 10 µmol/L CPT for 24, 48, and 72 hours, the apoptosis rates of the DU145 cells were (29.42 ± 4.51), (55.07 ± 5.67) and (70.84 ± 4.66)%, respectively, significantly higher than (3.1 ± 2.48)% in the control group (P < 0.05). The expression of metadherin was remarkably downregulated at the transcription and translation levels (P < 0.05) and the expressions of the AKT signaling pathway and the Bcl-2 protein were markedly inhibited in the DU145 cells after treated with 10 µmol/L CPT for 48 hours (P < 0.05).
CONCLUSIONCPT can inhibit the proliferation and induce the apoptosis of DU145 prostate cancer cells, which may be associated with its suppression of the downstream PI3K/AKT signaling pathway by reducing the expression of metadherin in the DU145 cells.
Apoptosis ; drug effects ; Cell Adhesion Molecules ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Abietane ; pharmacology ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Humans ; In Situ Nick-End Labeling ; Male ; Neoplasm Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; Time Factors
4.Effect of the positive sera of autoantibodies against the human beta1-adrenoceptor from patients with congestive heart failure on activity of L-type Ca2+ channel in guinea pig cardiac myocytes.
Shu-yan WANG ; Xin-chun YANG ; Guo-bin MIAO ; Xiu-lan LIU ; Lin ZHANG
Acta Academiae Medicinae Sinicae 2005;27(3):332-336
OBJECTIVETo investigate the effect of the positive sera of autoantibodies against the human beta1-adrenoceptor from patients with congestive heart failure on activity of L-Type Ca2+ channel in guinea pig cardiac myocytes.
METHODUsing whole cell patch-clamp technique, we quantitatively researched the ionic intensity and density of L-type Ca2+ channel (ICa-L).
RESULTSThe beta-adrenocepter agonist isoprenaline increased the ICa-L peak intensity and density from (997.09 +/- 227.5) pA and (8.20 +/- 0.86) pA/pF to (2241.01 +/- 348.5) pA and (18.98 +/- 1.18) pA/pF, respectively (P < 0.01). The positive sera of autoantibodies against the beta1-adrenoceptor could also increase ICa-L peak intensity and density from (963.57 +/- 207.56) pA and (8.14 +/- 0.72) pA/pF to (1382.41 +/- 241.36) pA and (11.70 +/- 1.03) pA/pF (P < 0.01). Esmolol, a beta1-adrenoceptor antagonist blocked these effects of isoprenaline and autoantibodies.
CONCLUSIONSHuman cardiac positive sera of autoantibodies against the beta1-adrenoceptor has an isoproterenol-like effect on cardiac myocytes receptor. It may participate in the pathophysiologic process of cardiac myocytes.
Animals ; Autoantibodies ; blood ; Calcium Channels, L-Type ; metabolism ; Female ; Guinea Pigs ; Heart Failure ; immunology ; Male ; Myocytes, Cardiac ; metabolism ; Patch-Clamp Techniques ; Receptors, Adrenergic, beta ; immunology
5.An improved association-mining research for exploring Chinese herbal property theory: based on data of the Shennong's Classic of Materia Medica.
Rui JIN ; E-mail: ZHANGBING6@263.NET. ; Zhi-jian LIN ; Chun-miao XUE ; Bing ZHANG
Journal of Integrative Medicine 2013;11(5):352-365
Knowledge Discovery in Databases is gaining attention and raising new hopes for traditional Chinese medicine (TCM) researchers. It is a useful tool in understanding and deciphering TCM theories. Aiming for a better understanding of Chinese herbal property theory (CHPT), this paper performed an improved association rule learning to analyze semistructured text in the book entitled Shennong's Classic of Materia Medica. The text was firstly annotated and transformed to well-structured multidimensional data. Subsequently, an Apriori algorithm was employed for producing association rules after the sensitivity analysis of parameters. From the confirmed 120 resulting rules that described the intrinsic relationships between herbal property (qi, flavor and their combinations) and herbal efficacy, two novel fundamental principles underlying CHPT were acquired and further elucidated: (1) the many-to-one mapping of herbal efficacy to herbal property; (2) the nonrandom overlap between the related efficacy of qi and flavor. This work provided an innovative knowledge about CHPT, which would be helpful for its modern research.
Data Mining
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Drugs, Chinese Herbal
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Humans
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Materia Medica
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Medicine, Chinese Traditional
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Qi
6.Research and analysis to Shui nationality medicine treatment orthopedics & traumatology.
Jian-Shan HU ; Pu LI ; Yong YANG ; Xin-Chun CHEN ; Li LIN
China Journal of Chinese Materia Medica 2013;38(10):1618-1620
To investigated Shui nationality folk medicine's awareness to orthopedics & traumatology, the history of orthopedics & traumatology treatment, Shui nationality folk doctors' practicing medicine, heritage, diagnosis and treatment methods and tools, etc, through investigated drug resources category and distribution characteristics of Shui nationality medicine to orthopedics & traumatology treatment, explored and finished Shui nationality medicine orthopedics & traumatology treatment theoretical system. After more than 5 years' exploration and finishing, preliminarily formed the theoretical system framework and medicine application characteristics of Shui nationality medicine treating orthopedics & traumatology. Shui nationality medicine treatment orthopedics & traumatology has distinctive national style, and worthy to further exploration and research.
Bone Diseases
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ethnology
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history
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therapy
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China
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ethnology
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History, 20th Century
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History, 21st Century
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Humans
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Orthopedics
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history
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methods
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Religion and Medicine
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Traumatology
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history
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methods
7.Patient-controlled intravenous analgesia with sufentanil and fentanyl after thoracotomy: a comparative study.
Chun-shui LIN ; Gang LU ; Luo-yang RUAN ; Miao-ning GU
Journal of Southern Medical University 2006;26(2):240-244
OBJECTIVETo evaluate the clinical efficacy of sufentanil and fentanyl at equivalent dose for patient-controlled intravenous analgesia (PCIA) after thoracotomy.
METHODSSixty ASA I-II patients (20-60 years of age) undergoing radical operation for lung or esophageal cancer were randomly divided into sufentanil intravenous analgesia group (group S, with sufentanil 1 microg/ml) and fentanyl intravenous analgesia group (group F, fentanyl 10 microg/ml). PCIA was administered with background infusion of 2.5 ml/h, bolus injection of 2.5 ml and lockout time of 15 min. The pain intensity according to visual analogue scale (VAS), cumulative analgesic consumption (CAC), sedative scores and side effects at 24 and 48 h after administration were recorded. SpO(2), respiratory rate (RR), blood pressure (BP) and ECG were continuously monitored.
RESULTSThere were no significant differences in CAC between the two groups, but he VAS was lower in group S than in group F (P<0.05) and the sedative efficacy was superior in group S (P<0.05). The incidence of nausea and vomiting in group S was lower than that in group F (P<0.05). No significant differences were observed in SpO(2), RR, heart rate and mean arterial pressure between the two groups.
CONCLUSIONPCIA with sufentanil provides better efficacy of analgesia and sedation with lower incidence of nausea and vomiting than with fentanyl in postoperative patients with thoracotomy.
Adult ; Analgesia, Patient-Controlled ; Esophageal Neoplasms ; surgery ; Female ; Fentanyl ; administration & dosage ; adverse effects ; Humans ; Infusions, Intravenous ; Lung Neoplasms ; surgery ; Male ; Middle Aged ; Nausea ; chemically induced ; Pain, Postoperative ; drug therapy ; Sufentanil ; administration & dosage ; adverse effects ; Thoracotomy ; Vomiting ; chemically induced
8.Advances in studies on eudistomin marine alkaloids.
Xiao-chun DONG ; Yu-ping MIAO ; Zhi-gang LIN ; Fan YU ; Ren WEN
Acta Pharmaceutica Sinica 2003;38(11):876-880
9.Effect of propofol at uptake equilibrium on γ-aminobutyric acid in different cerebral regions in dogs.
Yan WANG ; Chun-Shui LIN ; Miao-Ning GU ; Gao-Feng GUO ; Zhi-Feng ZHOU ; Ying CHEN
Journal of Southern Medical University 2012;32(3):427-429
OBJECTIVETo investigate the effect of propofol at doses for different anesthesia depths on γ-aminobutyric acid (GABA) in different cerebral regions at propofol uptake equilibrium in dogs.
METHODSTwelve 12-18-month-old healthy hybrid dogs weighing 10-12 kg were randomly divided into light anesthesia group (n=6) and deep anesthesia group (n=6) with a single bolus dose of propofol (5.5 and 7.0 mg/kg, respectively) completed in 15 s followed by intravenous propofol infusion at a constant rate (55 and 70 mg·kg(-1)·h(-1), respectively). Blood samples (2 ml) were taken from the internal carotid artery and jugular vein to measure plasma propofol concentrations 50 min after the start of the infusion. The dogs were then sacrificed and tissues were taken from different brain regions and the cervical cord to measure GABA concentrations using high-pressure liquid chromatography (HPLC).
RESULTSThe plasma propofol concentrations in internal carotid artery and jugular vein were similar in both light anesthesia group (3.00 ± 0.31 and 3.10 ± 0.51 µg/ml, respectively, P>0.05) and deep anesthesia group (6.41 ± 0.05 and 6.40 ± 0.11 µg/ml, respectively, P>0.05). GABA concentrations in the brain regions were significantly higher in deep anesthesia group than in light anesthesia group (P<0.05). The dorsal thalamus and hypothalamus showed greater GABA variations [(83.83 ± 2.230%) and (85.83 ± 1.72)%] compared to other brain regions at different anesthesia depths (P<0.05).
CONCLUSIONSIn both groups, plasma propofol concentrations in the internal carotid artery and internal jugular vein reach equilibrium at 50 min of propofol infusion. The variation of GABA is associated with the anesthesia depth of propofol, and GABA variation in the dorsal thalamus and hypothalamus plays an important role in propofol anesthesia.
Anesthetics, Intravenous ; pharmacokinetics ; Animals ; Brain ; metabolism ; Dogs ; Female ; Male ; Propofol ; blood ; pharmacokinetics ; gamma-Aminobutyric Acid ; metabolism
10.Protective effects of lidocaine against lung injury after hemorrhagic shock in rabbits.
Luo-yang RUAN ; Chun-shui LIN ; Ying-ying LIU ; Miao-ning GU
Journal of Southern Medical University 2007;27(4):543-545
OBJECTIVETo study the protective effect of lidocaine against lung injury after hemorrhagic shock in rabbits.
METHODSEighteen healthy rabbits were randomly divided into 3 groups (n=6), namely lidocaine group (group L), hemorrhagic shock group (group H) and control group (group C). Hemorrhagic shock model was established in rabbits in groups L and H, and the venous blood samples were collected for measurement of plasma malondialdehyde (MDA) and superoxidedismutase (SOD) before phlebotomy (T0), 2 h after hemorrhagic shock (T1) and 2 h after resuscitation (T2). Blood samples were also taken for measurement of MDA and SOD at the same time points in group C. The wet to dry weight ratio of the lung (W/D) was measured at T2.
RESULTSMDA level was significantly lower while SOD level significantly higher in group L than in group H (P<0.05). The W/D ratio in group L was reduced significantly as compared with that in group H (P<0.05).
CONCLUSIONLidocaine can remarkably alleviate lung injury after hemorrhagic shock by inhibiting MDA production and increasing SOD content.
Animals ; Disease Models, Animal ; Lidocaine ; pharmacology ; Lung ; drug effects ; metabolism ; Lung Injury ; prevention & control ; Malondialdehyde ; blood ; Rabbits ; Shock, Hemorrhagic ; drug therapy ; Superoxide Dismutase ; blood