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1.
BMC Pregnancy Childbirth ; 23(1): 820, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38012579

ABSTRACT

BACKGROUND: Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients. AIMS: To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response. METHODS: From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count < 30 × 109/L who did not respond to steroids and/or intravenous immunoglobulin were retrospectively analysed. Of these patients, 33 received rhTPO treatment (rhTPO group) while 48 did not (control group). Baseline characteristics, haematological disease outcomes before delivery, obstetric outcomes, and adverse events were compared between groups. In the rhTPO group, a generalised estimating equation (GEE) was used to investigate the factors influencing the response to rhTPO treatment. RESULTS: The baseline characteristics were comparable between both groups (P > 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5-67.5] vs. 25 [19-29] × 109/L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P < 0.001). Gestational weeks of delivery (37.6 [37-38.4] vs 37.1 [37-37.2] weeks, P = 0.001) were longer in the rhTPO group than in the control group. The rates of caesarean section, postpartum haemorrhage, foetal or neonatal complications, and complication types in both groups were similar (all P > 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment. CONCLUSION: rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.


Subject(s)
Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Female , Humans , Pregnancy , Cesarean Section , Cohort Studies , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Recombinant Proteins/therapeutic use , Retrospective Studies , Thrombopoietin/therapeutic use
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 301: 122963, 2023 Nov 15.
Article in English | MEDLINE | ID: mdl-37302200

ABSTRACT

Aflatoxin B1 (AFB1) is usually the major aflatoxin produced by toxigenic strains and has been identified the most potent natural carcinogen. Here, a SERS/fluorescence dual-mode nanosensor has been designed while gold nanoflowers (AuNFs) was used as substrate for the detection of AFB1. AuNFs exhibited excellent SERS enhancement effect as well as the good fluorescence quenching effect which made the dual signal detection possible. First, the surface of AuNFs was modified with AFB1 aptamer via Au-SH group. Then, the complementary sequence functionalized with Cy5 (the signal molecule) was attached to AuNFs based on the base complementary pairing principle. On this case, Cy5 was close to AuNFs, the SERS intensity was greatly enhanced and the fluorescence intensity was quenched. After incubation with AFB1, the aptamer was preferentially combined to its target AFB1. Thus, the complementary sequence detached from AuNFs which caused the SERS intensity of Cy5 decreased while its fluorescence effect recovered. Then, the quantitative detection was realized with two optical properties. The LOD was calculated to be 0.03 ng/mL. It was a convenient and fast detection method which expanded the application of nanomaterials based multi-signal simultaneous detection.


Subject(s)
Aptamers, Nucleotide , Metal Nanoparticles , Aflatoxin B1/analysis , Gold/chemistry , Aptamers, Nucleotide/chemistry , Limit of Detection , Metal Nanoparticles/chemistry
3.
Anal Chim Acta ; 1240: 340776, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36641156

ABSTRACT

Histamine is a significant biomarker to assess the freshness of fish products. In this study, a novel MOF-based SERS sensor for histamine determination was synthesized by wrapping PVP-capped Au nanoflowers with a ZIF-67 shell (Au NFs@ZIF-67). The highly branched Au NFs core exhibited a strong electromagnetic field enhancement effect and provided an ultra-sensitive SERS fingerprint spectrum, while ZIF-67 shell was the contributor to enrich the target and stabilize the substrate. The morphology of the core-shell structures can be easily controlled by the concentrations of the capping agent PVP and MOF precursor Co ion. Consequently, 4-MBA pre-grafted on the optimized SERS substrate can act as the Raman internal standard (IS) to eliminate signal fluctuations through standardizing all spectra against its peak at 1074 cm-1. Moreover, as the specific receptor for histamine molecules, 4-MBA helped reach the low detection sensitivity, where the SERS intensity ratio, I1172/I1074 presented a good linear relationship towards the histamine concentrations (10-3-10-7 M) with the LOD of 0.87 × 10-7 M (R2 = 0.9930). Furthermore, the application in monitoring fish spoilage process demonstrated the feasibility and reliability of the developed sensor. This work provided a facile strategy to construct MOF-based SERS substrate as a potential platform for the shelf-life prediction of fish products.


Subject(s)
Metal Nanoparticles , Nanocomposites , Animals , Histamine , Reproducibility of Results , Sulfhydryl Compounds/chemistry , Fishes , Spectrum Analysis, Raman , Gold/chemistry , Metal Nanoparticles/chemistry
4.
Chin J Integr Med ; 28(12): 1088-1095, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36327049

ABSTRACT

OBJECTIVE: To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS). METHODS: PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 ß-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively. RESULTS: The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05). CONCLUSION: The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.


Subject(s)
Curcumin , Hyperandrogenism , Insulin Resistance , Ovarian Cysts , Ovarian Neoplasms , Polycystic Ovary Syndrome , Animals , Female , Rats , Cell Proliferation , Curcumin/pharmacology , Curcumin/therapeutic use , Follicle Stimulating Hormone , Glucose , Insulin Receptor Substrate Proteins/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Polycystic Ovary Syndrome/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Testosterone
5.
Front Nutr ; 9: 976400, 2022.
Article in English | MEDLINE | ID: mdl-36051900

ABSTRACT

Acrolein (ACR), an α, ß-unsaturated aldehyde, is a toxic compound formed during food processing, and the use of phenolics derived from dietary materials to scavenge ACR is a hot spot. In this study, rutin, a polyphenol widely present in various dietary materials, was used to investigate its capacity to scavenge ACR. It was shown that more than 98% of ACR was eliminated under the conditions of reaction time of 2 h, temperature of 80 °C, and molar ratio of rutin/ACR of 2/1. Further structural characterization of the formed adduct revealed that the adduct of rutin to ACR to form a cyclic hemiacetal compound (RAC) was the main scavenging mechanism. Besides, the stability of RAC during simulated in vitro digestion was evaluated, which showed that more than 83.61% of RAC was remained. Furthermore, the cytotoxicity of RAC against Caco-2 and GES-1 cells was significantly reduced compared with ACR, where the IC50 values of ACR were both below 20 µM while that of RAC were both above 140 µM. And the improvement of the loss of mitochondrial membrane potential (MMP) by RAC might be one of the detoxification pathways. The present study indicated that rutin was one of the potential ACR scavengers among natural polyphenols.

6.
Front Nutr ; 9: 893991, 2022.
Article in English | MEDLINE | ID: mdl-35578612

ABSTRACT

5-(Hydroxymethyl)-2-furfural (HMF), an active furfural, widely exists in various food products and has potential safety risks. It can be eliminated by occurring aldol condensation with α-unsubstituted ketones in the presence of catalysts. However, the elimination process between HMF and ketones from food is rarely studied. In this study, the adduct formation between HMF and zingerone (ZGR) catalyzed by proline was investigated. It revealed that the adduct formation led to 99.75% of HMF being trapped under the optimized reaction condition. Moreover, the in vitro digestion stability of HMF-ZGR adduct (HMZ) and its cytotoxicity against Caco-2 cells were evaluated. The results indicated that more than 75% of HMZ was remained after a three-stage simulated digestion. Following 24 and 48 h of incubation, HMZ exhibited cytotoxicity against Caco-2 cells with IC50 values of 41.47 ± 5.33 and 25.39 ± 3.12 mM, respectively, versus 35.39 ± 4.03 and 19.17 ± 2.10 mM by HMF.

7.
J Mater Chem B ; 10(4): 571-581, 2022 01 26.
Article in English | MEDLINE | ID: mdl-34994374

ABSTRACT

The monitoring of small-molecule thiols (especially glutathione) has attracted widespread attention due to their involvement in numerous physiological processes in living organisms and cells. In this work, a dual-mode nanosensor was designed to detect small-molecule thiols, which is based on the "on-off" switch of fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS). Briefly, DNA was modified by Cy5 (signal probe) and disulfide bonds (recognition element). Gold nanoflowers (AuNFs) were used as the fluorescence-quenching and SERS-enhancing substrate. However, small-molecule thiols can cleave disulfide bonds and release short Cy5-labeled chains, causing the recovery of the fluorescence signal and a decrease of the SERS signal. The nanosensor showed a sensitive response to small-molecule thiols represented by GSH, with a linear range of 0.01-3 mM and a detection limit of 913 nM. In addition, it competed with other related biological interferences and presented good stability and better selectivity towards small-molecule thiols. Most importantly, the developed nanosensor had been successfully applied to in situ imaging and quantitative monitoring of the concentration of small-molecule thiols which changed during T-2 toxin-induced apoptosis in HeLa cells. Meanwhile, nanosensors are also versatile with their potential applications and can be easily extended to the detection and imaging of other human cell lines. The proposed method combines the dual advantages of fluorescence and SERS, which has broad prospects for in situ studies of physiological processes involving small-molecule thiols in biological systems.


Subject(s)
Apoptosis , DNA/chemistry , Fluorescence , Gold/chemistry , Metal Nanoparticles/chemistry , Sulfhydryl Compounds/analysis , Fluorescence Resonance Energy Transfer , HeLa Cells , Humans , Materials Testing , Spectrum Analysis, Raman
8.
Carbohydr Polym ; 267: 118194, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34119161

ABSTRACT

Allium sativum L. is a widely distributed plant used as a spice, vegetable and medicine. In this study, one novel water-soluble polysaccharide (GBP-1a), with a molecular weight of 15.0 kDa, was isolated from the scape of A. sativum (garlic bolt). GBP-1a consists of galactose, glucose and arabinose at a ratio of 73.29:4.36:1.70. It has a backbone, which is composed of 1,4-linked Galp, with 1,2,6-linked Galp branches and 1-linked Glcp residue. In addition, the anti-oxidant activities of GBP-1a, as well as the two main polysaccharide fractions on ABTS radicals, metal ions and superoxide anion radicals, were evaluated in vitro. This study added new data to the study of polysaccharides from garlic bolt.


Subject(s)
Free Radical Scavengers/chemistry , Garlic/chemistry , Polysaccharides/chemistry , Carbohydrate Sequence , Free Radical Scavengers/isolation & purification , Molecular Weight , Polysaccharides/isolation & purification
9.
Zhongguo Zhen Jiu ; 37(8): 814-818, 2017 Aug 12.
Article in Chinese | MEDLINE | ID: mdl-29231339

ABSTRACT

OBJECTIVE: To observe the efficacy differences between acupoint catgut embedding combined with ginger-partitioned moxibustion and regular acupuncture on chronic fatigue syndrome (CFS) of spleen-kidney yang deficiency syndrome, and to explore its effects on T lymphocyte subsets and activity of NK cell. METHODS: A total of 60 patients with CFS of spleen-kidney yang deficiency syndrome were randomly divided into a catgut embedding combined with ginger-partitioned moxibustion (CECGP) group and a regular acupuncture group, 30 cases in each one. The patients in the CECGP group were treated with acupoint catgut embedding combined with ginger-partitioned moxibustion; the acupoint catgut embedding was applied at Guanyuan (CV 4), Shenshu (BL 23), Pishu (BL 20), Zusanli (ST 36), Qihai (CV 6), once a week, while the ginger-partitioned moxibustion was applied at Guanyuan (CV 4), Qihai (CV 6) and Zusanli (ST 36), once every three days for consecutive one month. The patients in the regular acupuncture group were treated with regular acupuncture at Guanyuan (CV 4), Shenshu (BL 23), Pishu (BL 20), Zusanli (ST 36), Qihai (CV 6), once a day, 6 treatments per week (one day for rest) for consecutive one month. The clinical symptom scores, fatigue scale-14 (FS-14), fatigue assessment instrument (FAI), laboratory test results and total effective rate were compared between the two groups before and after treatment. RESULTS: (1) After treatment, the clinical symptom scores, FS-14 and FAI were reduced in the two groups (all P<0.05); after treatment, the clinical symptom scores, FS-14 and FAI in the CECGP group were significantly lower than those in the regular acupuncture group (all P<0.05). (2) After treatment, the CD4+/CD8+, natural killer cell% (NK%), CD3+%, CD% were all increased in the two groups (all +4 P<0.05); the CD4+/CD8+, CD3+%, CD% in the CECGP group were significantly higher than those in the regular acupuncture group (all P<0.05). (3) After treatment, the total effective rate was 96.7% (29/30) in the CECGP group, which was similar to 93.3% (28/30) in the regular acupuncture group (P>0.05). CONCLUSIONS: The acupoint catgut embedding combined with ginger-partitioned moxibustion, which could effectively relieve the symptoms, regulate T lymphocyte subsets and the activity of NK cell, is an effective method for CFS of spleen-kidney yang deficiency syndrome.


Subject(s)
Catgut , Fatigue Syndrome, Chronic/therapy , Killer Cells, Natural/physiology , Moxibustion/methods , T-Lymphocyte Subsets/physiology , Yang Deficiency/therapy , Zingiber officinale , Acupuncture Points , Acupuncture Therapy/methods , Humans , Kidney , Spleen
10.
Zhongguo Zhen Jiu ; 37(8): 836-839, 2017 Aug 12.
Article in Chinese | MEDLINE | ID: mdl-29231343

ABSTRACT

OBJECTIVE: To observe the efficacy differences between acupoint catgut embedding combined with auricular point pressure with beans and nilestriol on menopausal syndrome of liver-kidney deficiency type, and to explore their effects on estradiol (E2). METHODS: Sixty patients with menopausal syndrome of liver-kidney deficiency type were randomly divided into an acupoint stimulation group and a medication group, 30 cases in each group. The patients in the acupoint stimulation group were treated by acupoint catgut embedding at Taixi (KI 3), Sanyinjiao (SP 6), Shenshu (BL 23), Ganshu (BL 18) and Taichong (LR 3), combined with auricular point pressure at Gan (CO12), Shen (CO10), Neifenmi (CO18), Shenmen (TF4), Pizhixia (AT4); the treatment was given once a week for consecutive four weeks. The patients in the medication group were treated with oral administration of nilestriol, 1 mg, once a day, combined with oral administration of oryzanol, 20 mg, three times per day for consecutive four weeks. The clinical symptom score was compared between the two groups before and after treatment as well as in follow-up visit. The level of E2 was obserced before and after treatment, and the clinical effect was compared. RESULTS: (1) Compared before treatment, the clinical symptom score in the two groups was significantly reduced after treatment and in follow-up visit (all P<0.05); In follow-up visit, the clinical symptom score in the acupoint stimulation group was significantly lower than that in the medication group (P<0.05). The different value before treatment and at follow-up in the acupoint stimulation group was better than that in the medication group (P<0.05). (2) Compared before treatment, the level of E2 in the two groups were increased after treatment (both P<0.05); compared before and after treatment, the difference in the treatment group was significantly higher than that in the medication group (P<0.05). (3) After treatment, the total effective rate was 93.33% (28/30) in the acupoint stimulation group, which was similar to 90.00% (27/30) in the medication group (P>0.05). CONCLUSIONS: Compared with nilestriol, acupoint catgut embedding combined with auricular point pressure with beans could better improve clinical symptoms for patients with menopausal syndrome of liver-kidney deficiency type, and increased the level of E2.


Subject(s)
Acupuncture Points , Acupuncture, Ear/methods , Catgut , Menopause , Drug Therapy, Combination/methods , Estradiol/deficiency , Estrogens/therapeutic use , Female , Humans , Kidney , Liver , Phenylpropionates/therapeutic use , Quinestrol/analogs & derivatives , Quinestrol/therapeutic use , Syndrome , Treatment Outcome , Yang Deficiency/complications
11.
Theriogenology ; 94: 48-58, 2017 May.
Article in English | MEDLINE | ID: mdl-28407860

ABSTRACT

The present study was undertaken to examine the effect of MG132, a proteasome inhibitor, on the in vitro development, zygotic genome activation (ZGA) and epigenetic modification of Debao porcine somatic cell nuclear transfer (SCNT) embryos. Treatment of oocytes with 1 µM MG132 from 30 h to 42 h of maturation and SCNT embryos with 5 µM MG132 for 2 h after fusion resulted in higher blastocyst yield (36.5%) of SCNT embryos compared with the control group (11.0%). The ZGA of SCNT embryos at 2- and 4-cell stages was also enhanced by MG132 treatment through altering the RNA pol II status and increasing the expression of eIF3A and TFIIA. Meanwhile, MG132 treatment also resulted in increase of inner cell mass (ICM) and trophectoderm (TE) and total cell numbers and decrease of apoptotic cell numbers of SCNT blastocysts. Expression of BCL-2, OCT4, NANOG and CDX2 in SCNT blastocysts developed from SCNT embryos and oocytes treated with MG132 was increased significantly (P < 0.01), while the expression of pro-apoptotic BAX gene was suppressed significantly (P < 0.01). In addition, MG132 treatment not only affected the expression patterns of H3K9 acetylation, H3K4 and H3K9 trimethylation, but also regulated the relative expression of SMYD3, ASH2L, KDM5B, HAT1, HDAC1 and HDAC2 of Debao porcine SCNT embryos. These results demonstrate that MG132 treatment can improve the developmental potential of Debao porcine SCNT embryos through regulating the expression of genes related to histone acetylation and the processes of ZGA.


Subject(s)
Embryonic Development/drug effects , Leupeptins/pharmacology , Proteasome Inhibitors/pharmacology , Swine/embryology , Acetylation/drug effects , Animals , Apoptosis/drug effects , Blastocyst/drug effects , Blastocyst Inner Cell Mass/drug effects , Embryo Culture Techniques/veterinary , Epigenesis, Genetic , Gene Expression Regulation, Developmental/drug effects , Histones/metabolism , Nuclear Transfer Techniques/veterinary
13.
Int J Radiat Oncol Biol Phys ; 85(1): e47-54, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23122981

ABSTRACT

PURPOSE: Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. METHODS AND MATERIALS: Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. RESULTS: IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). CONCLUSIONS: IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.


Subject(s)
Nasopharyngeal Neoplasms/radiotherapy , Quality of Life , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma , Chemoradiotherapy/methods , China , Dose Fractionation, Radiation , Female , Humans , Language , Male , Middle Aged , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/diagnostic imaging , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Radiotherapy, Intensity-Modulated/mortality , Surveys and Questionnaires , Tomography, X-Ray Computed , Treatment Outcome , Tumor Burden/radiation effects
14.
J Cardiovasc Pharmacol ; 54(5): 437-44, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19940642

ABSTRACT

In the present study, we examined the ability of a chemically synthesized compound based on the structure of leonurine, a phytochemical component of Herba leonuri, to protect H9c2 rat ventricular cells from apoptosis induced by hypoxia and serum deprivation, as a model of ischemia. The results revealed a concentration-dependent increase in cell viability associated with leonurine treatment, accompanied by a consistent decline in lactate dehydrogenase leakage into the culture medium. The fraction of annexin V-fluorescein isothiocyanate-positive cells was increased by hypoxia but reduced by leonurine. These changes were associated with increased expression of the antiapoptotic gene, Bcl-2, and reduced expression of the proapoptotic gene, Bax. Leonurine also reduced the cytosolic Ca overload induced by hypoxia. These results suggest that leonurine elicits potent cardioprotective effects in H9c2 cells, and these effects may be mediated by inhibition of intracellular Ca overload and apoptosis during hypoxia.


Subject(s)
Apoptosis/drug effects , Cardiotonic Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Gallic Acid/analogs & derivatives , Myocytes, Cardiac/drug effects , Animals , Blotting, Western , Calcium/metabolism , Cell Hypoxia , Cell Line , Cell Survival/drug effects , Cytochromes c/metabolism , Cytosol/drug effects , Cytosol/metabolism , Flow Cytometry , Gallic Acid/pharmacology , Heart Ventricles/cytology , Heart Ventricles/metabolism , Heart Ventricles/pathology , Microscopy, Fluorescence , Mitochondria, Heart/drug effects , Mitochondria, Heart/enzymology , Mitochondria, Heart/metabolism , Molecular Structure , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Rats , Superoxide Dismutase/biosynthesis , bcl-2-Associated X Protein/biosynthesis
15.
Biol Pharm Bull ; 32(8): 1406-10, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19652381

ABSTRACT

Hydrogen sulfide (H(2)S), as an endogenous gas signaling molecule with important biological function that has been found recently, may play a protection in ischemic reperfusion (I/R) myocardium. We investigated the cardioprotective effect of H(2)S in rats model of ischemic reperfusion in vivo and a probably influence on the expression of survivin, an anti-apoptosis gene. Animals were randomly divided into 3 groups and received either vehicle, sodium hydrosulfide (NaHS) or DL-propargylglycine (PAG) respectively everyday for 1 week before surgery and the treatment continued for a further 2 d after I/R till the animals were sacrificed. We investigated the plasma H(2)S concentration and blood pressure, with the electrocardiogram (ECG) together, to prove the effect of H(2)S to the heart function. We also compared the heart infarct size and the expression of an anti-apoptosis gene, survivin, among groups. As the data shown, the NaHS group had great improvement in blood pressure and electrocardiogram situation. And the remarkable shrink of the infarct size and up-regulation of survivin in NaHS group comparing with the other two groups also showed the cardio protective effect of H(2)S in our study.


Subject(s)
Cardiotonic Agents/therapeutic use , Gene Expression/drug effects , Hydrogen Sulfide/blood , Microtubule-Associated Proteins/genetics , Myocardial Reperfusion Injury/prevention & control , Myocardium/metabolism , Sulfides/therapeutic use , Alkynes/pharmacology , Animals , Apoptosis/drug effects , Blood Pressure/drug effects , Blotting, Western , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/pharmacokinetics , Cystathionine gamma-Lyase/antagonists & inhibitors , Cystathionine gamma-Lyase/metabolism , Disease Models, Animal , Electrocardiography , Glycine/analogs & derivatives , Glycine/pharmacology , Immunohistochemistry , Male , Myocardial Infarction/etiology , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Myocardial Infarction/prevention & control , Myocardial Reperfusion Injury/complications , Myocardial Reperfusion Injury/genetics , Myocardial Reperfusion Injury/pathology , Myocardium/enzymology , Myocardium/pathology , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Sulfides/administration & dosage , Sulfides/pharmacokinetics , Survivin
16.
J Recept Signal Transduct Res ; 29(3-4): 182-94, 2009.
Article in English | MEDLINE | ID: mdl-19604037

ABSTRACT

Targeting dysregulated signaling pathways in tumors has led to the development of a novel class of signal transduction inhibitors, including inhibitors of the epidermal growth factor (EGF) receptor (EGFR). To dissect oncogenic pathways, identify key pathway determinants, and evaluate the efficacy of targeted agents, it is vital to develop technologies that allow the detection of temporal signaling events under physiological conditions. Here we report the application of a label-free optical biosensor to reveal the rapid response of cancer cells to EGF, expressed as a dynamic mass redistribution (DMR) signal. In response to EGF, squamous cell carcinoma of the head and neck cells exhibited a rapid rise in DMR signal, whereas lung adenocarcinoma cells showed a biphasic DMR profile, suggesting a cell type-dependent DMR response. Pharmacological studies suggested the importance of EGFR and the phosphatidylinositol-3 kinase pathway in mediating the EGF-induced DMR response. The defined DMR signatures offer a simple yet sensitive tool for evaluating EGFR-targeted agents, as shown with gefitinib and erlotinib. The assay can also be used for cell-based high-throughput screening of EGF pathway inhibitors, as demonstrated by its robust performance in a 384-well plate format (Z' > 0.5). This technology is applicable to other oncogenic pathways for the discovery of novel therapeutic agents for the treatment of various cancers.


Subject(s)
Biosensing Techniques , ErbB Receptors/metabolism , Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/drug effects , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Epidermal Growth Factor/pharmacology , Erlotinib Hydrochloride , Gefitinib , Humans , Protein Kinase Inhibitors/pharmacology , Quinazolines/pharmacology , Signal Transduction/physiology
17.
Article in English | MEDLINE | ID: mdl-12168034

ABSTRACT

Incubation of rat hepatic sinusoidal cells with FITC-HDL(2), FITC-ox-HDL(2) and [(3)H]CE-HDL(2)(rHDL(2)), ox-rHDL(2) showed that binding of FITC-HDL(2) to the cells was competitive to ox-HDL(2), but not to HDL(2). The cell-endocytic fluorescence strength (FS) of FITC-HDL(2) and radioactivity of ox-rHDL(2) were 45.5% of that of FITC-HDL(2) and 61.4% of that of rHDL(2), respectively. Endocytic FS and radioactivity were mainly in TCA-precipitable and supernatant part, respectively. The cell-released FS and radioactivity were 67.7% and 10.9% of the cell-endocytic FS and the radioactivity, respectively, and both of them were mainly TCA-precipitable. These results suggest that: (1) There is probably an ox-HDL receptor on the surface of rat hepatic sinusoidal cells, which is different from HDL receptor. (2) The metabolic behaviour of ox-rHDL(2) in the cells is similar to HDL(2). Both of them do not take a lysosomal pathway. Apoproteins and CE components dissociate from endocytic lipoprotein in the cells. After the cells have taken up most of CE, the residual CE recombines with apolipoprotein to form a lipoprotein and is released from the cells by retroendocytosis. (3) Oxidative modification of HDL(2) weakens its ability to cholesterol reverse transport.

18.
Article in English | MEDLINE | ID: mdl-12232594

ABSTRACT

The recombined (3)H-CE-HDL(2)(rHDL(2)) keeps the biological activities of the native HDL(2). After rat hepatic sinusoidal cells were incubated with rHDL(2) at 37 degrees for 3 h (normal group), the cell-endocytic cpm was 995-/+147(mean-/+s, n=2). After the cells were further incubated for 2 h, the cell-release TCA-precipitable cpm and the TCA-supernatant cpm were 78-/+32 and 12-/+9 respectively. These values were 339-/+62, 19-/+11 and 9-/+5 respectively in the acetylimidazole-modified group, and 542-/+78, 34-/+14 and 9-/+8 respectively in the heparin-pretreated group. Our results suggested that: (1) Rat hepatic sinusoidal cells internalize HDL(2) and take up HDL(2)-CE by its HDL receptor, and HDL(3) was secreted out of the cells by retroendocytosis. (2) Hepatic lipase (HL) induces directly the selective uptake of HDL(2)-CE by the cells. (3) There is cooperation between the HDL receptor and HL in the selective uptake of HDL(2)-CE by the cells.

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