Retinoid resistance has limited clinical activity of retinoids as differentiation-inducing and apoptosis-inducing drugs. The present study was designed to investigate whether celecoxib (selective COX-2 inhibitor) has effects on cellular retinoid sensitivity of human colon cancer cell lines and its possible mechanism. Cell viability was measured by MTT assay. Apoptosis was detected by Annexin-V/PI staining and flow cytometry assay. PGE2 production was measured by ELISA assay. Expression of RARbeta was assayed by Western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, and the addition of PGE2 did not affect the number of apoptotic cells induced by the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA on both cell lines. Western blotting showed that the expression of RARbeta in HT-29 cell lines increased in celecoxib group and combination group. And the addition of PGE2 did not affect the expression of RARbeta induced by celecoxib either. In conclusion, celecoxib increased expression of RARbeta and cellular ATRA sensitivity through COX-2-independent mechanisms, which may provide a potential strategy for combination therapy.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Celecoxib ; Cell Line, Tumor ; Cell Survival ; drug effects ; Colonic Neoplasms ; metabolism ; pathology ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Dinoprostone ; metabolism ; Drug Synergism ; HT29 Cells ; Humans ; Nitrobenzenes ; pharmacology ; Pyrazoles ; pharmacology ; Receptors, Retinoic Acid ; metabolism ; Sulfonamides ; pharmacology ; Tretinoin ; pharmacology

Aim To explore the effect of ZLY18 on angiotensin II-induced cardiac fibrosis and the underlying mechanism. Methods Ang II was used to induce cardiac fibrosis in vitro and in vivo. Cardiac fibroblasts were divided into blank control group, model group and medicine group. The medicine group was subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 1, 2, 5 μmol·L-1 respectively. C57BL/6 mice were randomly divided into control group, model group and medicine group. The medicine group were subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 10,20 and 50 mg·kg-1 respectively. Both the model group and the medicine group were given with Ang II to induce cardiac fibrosis. The changes of protein levels were detected by Western blot and immunofluorescence. The changes of cardiac function indexes in C57BL/6 mice were detected by small animal echocardiography. The morphology, cell arrangement and collagen fibers of cardiac fibroblasts were observed by tissue section staining and other methods. Results The model of Ang II-induced myocardial fibrosis was successfully established at the cell and animal levels, and ZLY18 treatment improved the elevated fibrosis-related protein caused by Ang II and abnormal cardiac function in mice. Moreover, ZLY18 was able to inhibit the increased phosphorylation of TGF-1 and Smad3 caused by Ang II and increased Smad2/3 nuclear entry, suggesting that the antifibrotic effect of ZLY18 might be related to the activation of TGF-1/Smads signaling pathway. Conclusions ZLY18 has a protective effect on Ang II-induced cardiac fibrosis. ZLY18 may inhibit TGF-β/Smads signaling pathway activation to exert anti-fibrotic effects.

OBJECTIVETo investigate the expression and its significance of retinoic acid receptor-beta (RAR-beta) in colorectal cancer.

METHODSRAR-beta was detected by immunohistochemistry methods and carcino-embryonic antigen (CEA) was tested by chemiluminescence immunoassay methods in normal tissues, paracancerous tissues and colorectal cancer tissues of 60 patients with colorectal cancer treated from January 2006 to January 2007. Above-mentioned data, together with the clinicopathological data of these 60 patients, were analyzed to figure out the expression and its significance of RAR-beta in colorectal cancer.

RESULTSThe expression rate of RAR-beta in tumor tissues (48%) was significantly lower than those in both normal tissues (87%) and paracancerous tissues (87%) (P < 0.05). And its expression was also significant lower in patients with lymph node metastasis (32%) and patients with advanced cancer (TNM stage III and IV) (29%) than in those without lymph nodes metastasis (60%) and those with early stage cancer (stage I and II) (69%). There was no significant differences among well, mildly and poorly differentiated cancer tissues. The CEA level rose in 20 patients, and its rising rate was remarkably higher in patients with lymph node metastasis (48%) and in patients with advanced cancer (52%) than those without lymph node metastasis (23%) and in early stage(14%).

CONCLUSIONSThe expression of RAR-beta decreases significantly in cancer tissues in patients with colorectal cancer, which may be related to the carcinogenesis of colorectal cancer; and its decreasing degree is correlated negatively with the lymph node metastasis and advanced clinicopathological stage. The expression level of RAR-beta may be a new prognostic indication of patients with colorectal cancer.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Male ; Middle Aged ; Receptors, Retinoic Acid ; metabolism ; Young Adult

OBJECTIVETo investigate the effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats.

METHODSMale SD rats weighing 250-300 g were randomly divided into 5 groups (n = 6), namely the control group, ouabain group, tizanidine group, combined ouabain and tizanidine injection group, and the antagonist group. Intrathecal catheter was implanted 7 days before spinal nerve ligation to establish the neuropathic pain model. Mechanical withdrawal threshold (MWT) before and after intrathecal administration of the agents was recorded in the rats. Isobolographic analysis was performed to evaluate the interactions between the agents.

RESULTSIntrathecal injection of ouabain (0.25-5 microg) or tizanidine (0.5-5 microg) alone produced dose-dependent analgesic effect against the neuropathic pain (P < 0.05). Isobolographic analysis revealed a synergistic interaction between ouabain and tizanidine. Intrathecal pretreatment with atropine (5 microg) or yohimbine (20 microg) antagonized the effects of ouabain and tizanidine administered alone or in combination (P < 0.05).

CONCLUSIONIntathecal injection of ouabain or tizanidine produces dose-dependent analgesic effects against neuropathic pain, and their synergistic effect after combined injection probably involves the cholinergic transmission and alpha2 receptor.

Analgesics ; administration & dosage ; Animals ; Clonidine ; administration & dosage ; analogs & derivatives ; Injections, Spinal ; Ouabain ; administration & dosage ; Pain ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves ; injuries

OBJECTIVETo investigate the clinical efficacy of noninvasive positive pressure ventilation (NPPV) in treatment of patients with arrhythmia complicated by sleep apnea syndrome (SAS).

METHODSOne hundred and thirty-five arrhythmia patients with polysomnography diagnosed SAS were randomly divided into NPPV group (69 cases) and control group (66 cases), the NPPV group was treated with standard medications and NPPV, and the control group was treated with standard medications. SAS related parameters were compared between the groups after 3 months therapy.

RESULTS(1) Epworth sleepiness scale (ESS) score, apnea-hypopnea index (AHI) and arousal index were significantly lower (8.25 ± 5.41 vs.4.08 ± 3.43, 39.95 ± 7.32 vs. 4.71 ± 1.80 and 39.69 ± 4.40 vs. 15.20 ± 2.05, P < 0.01) while not rapid eye movement (NREM) III and rapid eye movement stage of sleep time and lowest pulse oxygen saturation (LSaO2) were significantly higher in NPPV group than in control group [(4.53 ± 2.10)% vs. (16.78 ± 2.59)%,(8.37 ± 1.380)% vs. (15.25 ± 1.41)%, (77.15 ± 6.72)% vs. (93.35 ± 2.03)%, P < 0.01] after 3 months therapy. (2) Incidence of Sinus bradycardia, sinus tachycardia, sinus arrest, atrial premature beats, ventricular premature beats, paroxysmal atrial tachycardia, paroxysmal ventricular tachycardia, atrial fibrillation, II-III degree atrioventricular block, ST-T segment changes were reduced from 57.4%, 44.4%, 7.4%, 20.4%, 13.0%, 36.5%, 12.0%, 8.3%, 37.0%, 53.7% to 4.6%, 1.9%,0.0%, 3.7%, 2.8%, 7.0%, 0.9%, 0.0%, 1.9%, 4.6% (all P < 0.05) and the total number of arrhythmias happened at night were significantly lower (all P < 0.05) while the heart rate variability (HRV) were significantly higher (P < 0.01) in NPPV group than in control group; AHI was positively while LSaO2 was negatively correlated with the total night arrhythmia number (P < 0.01).

CONCLUSIONNoninvasive positive pressure ventilation is an effective therapy strategy for treating patients with arrhythmia complicated by sleep apnea syndrome.

Adult ; Aged ; Arrhythmias, Cardiac ; complications ; prevention & control ; Female ; Humans ; Male ; Middle Aged ; Noninvasive Ventilation ; Positive-Pressure Respiration ; Sleep Apnea Syndromes ; complications ; therapy

ObjectiveProlonged storage of packed red blood cells （PRBC） is reportedly associated with poor clinical outcomes in critically ill， trauma， and cardiac surgery patients. However， the impact of PRBC’s age on long-term oncological outcomes in cancer patients remains poorly defined. Here we retrospectively evaluated the effect of PRBC’s age on overall survival and biochemical recurrence in patients undergoing curative resection of hepatocellular carcinoma. MethodsA total of 1 221 qualified patients undergoing curative hepatectomy for HCC between August 1， 2008 and June 30， 2012 at the Sun Yat-sen University Cancer Center （Guangzhou， PR China） were divided into nontransfused or transfused group. Transfused patients were further divided according to PRBC storage duration （fresh PRBC group， ≤ 14 days； old PRBC group， > 14 days）. Overall survival （OS）， intrahepatic recurrence-free survival （IRFS）， extrahepatic metastasis-free survival （EMFS） were assessed and multivariate analyses were performed to evaluate the association of PRBC storage duration with cancer outcomes. ResultsA total of 251 （20.6%） patients received intraoperative PRBC transfusion. Of these， 112 and 125 patients were grouped in the fresh and the old PRBC groups， respectively. The Kaplan–Meier curves showed that both fresh PRBC group and old PRBC group had worse OS， IRFS， and EMFS than nontransfused group （P<0.001）. Cox regression analyses further indicated that old PRBC transfusion was an independent prognostic factor of OS （HR=1.417， P=0.049）， IRFS （HR=1.519， P=0.013） for patients with HCC； conversely， new PRBC transfusion was not. ConclusionIn patients undergoing curative hepatectomy， intraoperative transfusions of PRBC that had been stored for more than 2 weeks is independently associated with a significantly increased risk of intrahepatic recurrence and reduced overall survival.

Objective To study the epidemiological characteristics on the clustering nature of pandemic (H1N1) 2009 in China.Methods Time and place distribution of pandemic (H1N1) 2009on the nature of clustering through data from Public Health Emergency Management Information System were described.Results As of August 10,2010,2773 pandemic (H1N1) 2009 clusters,a total of 77363 cases (including 20 deaths) were reported in the mainland of China.The most reported number of clusters was from schools and kindergartens with the total number of 2498 (accounted for 90.08％ of the total number).Middle schools appeared the have the most clusters (1223,accounting for 48.96％ ).The number of clusters reported in the southern provinces (cities) accounted for 77.03％ of the total,and was more than that in the northern provinces (cities).Two reported peaks in the southern provinces (cities) were in June and November,2009,respectively.There was only one reported peakin the northern provinces in September,2009.Conclusion Time and place distribution characteristics on the clusters of pandemic (H1N1) 2009 were similar to the seasonal influenza,but the beginning of winter peak was much earlier and intensity of reporting was much higher on the clusters of pandemic (H1N1 ) 2009 than that of seasonal influenza.

Adult ; Angiomyolipoma ; diagnosis ; genetics ; Exons ; genetics ; Humans ; Kidney Neoplasms ; diagnosis ; genetics ; Male ; Mutation ; genetics ; Tuberous Sclerosis ; complications ; Tuberous Sclerosis Complex 2 Protein ; genetics ; Young Adult

Objective: In order to explore natural active ingredients of Scutellariae Radix and alleviate the pressure of traditional medicinal resources,this research aimmed to screen endophytic fungus strains from Scutellariae Radix which could transform baicalin into some active ingredients.Method: Taking fresh plants of Scutellariae Radix as strain resource,endophytic fungus strains were isolated by potato dextrose agar (PDA) plate separation,Scutellariae Radix powder selective culture and HPLC detection.Result: An endophytic fungus strain R3 was isolated and it can transform baicalin to baicalein and oroxylin A simultaneously in potato dextrose broth (PDB) contained 0.1% baicalin and the conversion rate reached 61.09% in 5 d cultured at 28℃ and 150 r·min^-1,molar ratio of baicalein and oroxylin A was 3:5.With the method of morphological analysis,microscopic identification and 18SrDNA sequence analysis,the bacterium was identified as Penicillium sp.R3. Conclusion: Penicillium sp.R3 can transform baicalin to baicalein and oroxylin A with certain research value and application value.