Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AI agents”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed2005

The treatment of relapsing primary nephrotic syndrome in children.

OBJECTIVE: To explore better therapy and reduce the rate of re-relapse of primary nephritic syndrome in children who had been treated with corticosteroids but relapsed. METHODS: Eighty relapsers were enrolled from Jan. 1994 to Apr. 2000, who were randomly divided into two groups. The treatment group (n=39) had been treated with tripterysium glucosides for three months, with the control group (n=41) members were treated with cyclophosphmide (CTX) by intermission intravenous pulse, with total dose of CTX not being more than 150 mg/kg. Prednisone, meanwhile, was given to both groups. The total treatment period of prednisone was prolonged by 12-18 months. RESULTS: After following up for 3-7 years, the re-relapse rates of both groups were observed. The re-relapse rate of the treatment group was 28.2% to 29.3% in the CTX-controlled group. The re-relapse rates between two groups were almost similar, and with no observed significant difference (P>0.05). The side effect of tripterysium glucosides was less than that of CTX. CONCLUSION: For the treatment of relapsing nephritic syndrome in children, the combination of tripterysium glucosides and prolonged corticosteroid therapy is as effective as the regimen of CTX plus prolonged use of prednisone.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Increased risk of rebleeding of peptic ulcer bleeding in patients with comorbid illness receiving omeprazole infusion.

BACKGROUND/AIMS: The study aimed to evaluate whether administration of intravenous omeprazole has different rebleeding rates for peptic ulcer bleeding of patients with and without comorbid illness. METHODOLOGY: A total of 80 patients with peptic ulcer bleeding were enrolled after therapeutic endoscopy to achieve hemostasis. Each patient had received omeprazole 80 mg bolus loading and 40 mg twice daily for three days (total dosage of 320 mg within 3 days). Two subgroups were divided, based on the absence (Group A) or presence (Group B) of one or more comorbid illnesses, such as chronic obstructive pulmonary disease, congestive heart failure, uremia, cirrhosis, diabetes mellitus, and old stroke. The 7-day and 28-day rebleeding rates were recorded. RESULTS: The presence of comorbid illness had a higher rebleeding rate than those without comorbid illness (7-day: 32.5 vs. 2.5%, p < 0.05; 28-day: 37.5 vs. 5.0%, p < 0.05). Patients with two or more comorbid diseases had an even higher risk of rebleeding than those with a single comorbid illness (66.7% vs. 26.5%, p < 0.05). CONCLUSIONS: Low-dose infusion of omeprazole can achieve favorable control of rebleeding in the patients with peptic ulcer bleeding but without comorbid diseases. As patients with comorbid illness had a higher risk of rebleeding, a higher dosage or prolonged duration of omeprazole infusion would be rationally indicated to prevent risk of rebleeding.

Adult↗
PubMed2005

[The role of reactive oxygen species in N-[4-hydroxyphenyl] retinamide induced apoptosis in bladder cancer cell lineT24].

OBJECTIVE: To study the mechanism of the apoptosis induced by N-[4-hydroxyphenyl] retinamide (4-HPR) in bladder cancer cell line T24, and the involvement of DNA damage and repair. METHODS: T24 cells were treated with 4-HPR at the concentration of 2.5, 5.0 and 10.0 micromol/L, and the cell grow inhibition was measured by cell counting assay. The fluorescent intensity of reactive oxygen species (ROS) was determined by spectrofluorometer. The apoptosis was measured by flow cytometry and DNA fragment assay. The expression of XRCC1 protein and activation of caspase-3 were detected by Western blot. RESULTS: 4-HPR induced apoptosis in T24 cell. A dose-dependent increase in the percentage of apoptosis cells was observed (1.8%, 4.0% and 10.5% respectively at 2.5, 5.0, 10.0 micromol/L 4HPR). In the meantime, ROS level in the cell was increased (peaked at 3 fold). It also caused down-regulation of the expression of XRCC1, and activation of caspase-3. Vitamin C effectively inhibited ROS rise induced by 4-HPR, and also partially inhibited cell growth, apoptosis, and down-regulation of the expression of XRCC1. CONCLUSION: The generation of ROS and DNA damage may be the major mechanism of the apoptosis of bladder cancer cell line T24 induced by 4-HPR.

Antineoplastic Agents↗
PubMed2006

[Screening of new HIV inhibitors based on the database of traditional Chinese medicine].

AIM: To report the preliminary result of the HIV inhibitor screening based on cheminformatics tools and the traditional Chinese medicine database. METHODS: Database search was carried out with saquinavir molecule as a template, further screening was made with docking. Detailed studies using molecular dynamics simulation of 50 ps and 200 ps were made with respect to a potential leading compound, leucovorin. RESULTS: The leucovorin molecule distinguished from other molecules as a potential drug candidate and is subject to extensive studies. The bonding profile and energy were calculated with MD simulations. CONCLUSION: Our results could be very helpful when we modify leucovorin or design new inhibitors against HIV.

Anti-HIV Agents↗
PubMed2005

Endocrine treatment options for advanced breast cancer--the role of fulvestrant.

For many years, tamoxifen has been the 'gold standard' amongst anti-oestrogen therapies for breast cancer. However, the selective aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, have demonstrated advantages over tamoxifen as first-line treatments for advanced disease. Anastrozole is also more effective as an adjuvant treatment in early, operable breast cancer and is being increasingly used in the adjuvant setting. Generally, the selective oestrogen receptor modulators (SERMs), such as toremifene, droloxifene, idoxifene, raloxifene, and arzoxifene, show minimal activity in tamoxifen-resistant disease and show no superiority over tamoxifen as first-line treatments. In addition to these agents, other treatment options for advanced disease include high-dose oestrogens and progestins. Response rates for high-dose oestrogens and tamoxifen are similar, but the use of oestrogens is limited by their toxicity profile. Consequently, there is a need for new endocrine treatment options for breast cancer, particularly for use in disease that is resistant to tamoxifen or AIs. Fulvestrant ('Faslodex') is a new type of steroidal oestrogen receptor (ER) antagonist that downregulates cellular levels of the ER and progesterone receptor and has no agonist activity. This paper reviews the key efficacy and tolerability data for fulvestrant in postmenopausal women in the context of other endocrine therapies and explores the potential role of fulvestrant within the sequencing of endocrine therapies for advanced breast cancer.

Anastrozole↗
PubMed2005

Aromatase inhibitors for the treatment and prevention of breast cancer.

In a review of current information on aromatase inhibitors (AIs) and their use in breast cancer treatment and prevention, published reports were obtained through a Medline search. Tamoxifen, a selective estrogen receptor modulator, is approved for use in metastatic breast cancer (MBC), the adjuvant treatment of breast cancer, and the prevention of breast cancer in women at high risk. The 50% reduction in breast cancer incidence seen with tamoxifen is significant for women at increased risk but is accompanied by notable toxicities such as thrombotic events and endometrial cancer. Therefore, the development of other effective agents with less toxicity would be a major advance in breast cancer prevention. Aromatase inhibitors, recently approved for the treatment of MBC and in the adjuvant setting, are proving to be slightly more effective than tamoxifen therapy. These drugs, approved for use in only postmenopausal women, inhibit the enzyme aromatase and thereby lower circulating functional estrogen. To date, the most concerning side effect of these agents is an increase in fracture rate. Compared with tamoxifen, thrombotic events and endometrial cancer rates are much lower. Ongoing data from the Arimidex, Tamoxifen, Alone or in Combination trial continue to favor anastrozole over tamoxifen in the reduction of primary contralateral breast cancers. This information has prompted breast cancer chemoprevention trials with AIs. Although tamoxifen is the gold standard for prevention therapy, results of ongoing studies may indicate a role for AIs in the prevention of breast cancer.

Adult↗
PubMed2000

Tumor response and estrogen suppression in breast cancer patients treated with aromatase inhibitors.

BACKGROUND: The rationale for the hormonal treatment of breast cancer (BC) is based on depriving tumor cells of estrogenic stimulation. Aromatase inhibitors (Als) block the conversion of peripheral tissue androgens to estrogens with different levels of potency. In an attempt to investigate the relationship between tumor response and estrogen suppression, we reviewed the hormonal and clinical data of two previous studies with formestane (250 and 500 mg i.m. fortnightly) in advanced BC patients. PATIENTS AND METHODS: Two hundred four BC patients were selected on the basis of the availability of records concerning their plasma estrone (El) and estradiol (E2) levels assessed at scheduled times. The degree of estrogen suppression and the best clinical response of each patient during the trials were considered. RESULTS: There was a positive and significant (P < 0.05) correlation between baseline and post-formestane E1 and E2 levels, with a decrease in the levels of both hormones irrespective of any antitumor response. In particular, the degree of plasma estrogen suppression was similar in the patients who experienced a complete remission and those with progressive disease (PD). CONCLUSIONS: The plasma estrogen suppression induced by aromatase inhibition is not the only mechanism accounting for its clinical activity. Many clinical trials have demonstrated that all AIs induce a similar antitumor response regardless of their potency, and further investigations are warranted in order to improve our understanding as to why the patients with PD also show a significant plasma estrogen suppression. It is possible that intratumoral aromatase activity may be a marker for selecting the BC patients most likely to respond to AI treatment.

Aged↗
PubMed2005

LuxS-based signaling affects Streptococcus mutans biofilm formation.

Streptococcus mutans is implicated as a major etiological agent in human dental caries, and one of the important virulence properties of this organism is its ability to form biofilms (dental plaque) on tooth surfaces. We examined the role of autoinducer-2 (AI-2) on S. mutans biofilm formation by constructing a GS-5 luxS-null mutant. Biofilm formation by the luxS mutant in 0.5% sucrose defined medium was found to be markedly attenuated compared to the wild type. Scanning electron microscopy also revealed that biofilms of the luxS mutant formed larger clumps in sucrose medium compared to the parental strain. Therefore, the expression of glucosyltransferase genes was examined and the gtfB and gtfC genes, but not the gtfD gene, in the luxS mutant were upregulated in the mid-log growth phase. Furthermore, we developed a novel two-compartment system to monitor AI-2 production by oral streptococci and periodontopathic bacteria. The biofilm defect of the luxS mutant was complemented by strains of S. gordonii, S. sobrinus, and S. anginosus; however, it was not complemented by S. oralis, S. salivarius, or S. sanguinis. Biofilm formation by the luxS mutant was also complemented by Porphyromonas gingivalis 381 and Actinobacillus actinomycetemcomitans Y4 but not by a P. gingivalis luxS mutant. These results suggest that the regulation of the glucosyltransferase genes required for sucrose-dependent biofilm formation is regulated by AI-2. Furthermore, these results provide further confirmation of previous proposals that quorum sensing via AI-2 may play a significant role in oral biofilm formation.

Bacterial Proteins↗
PubMed1975

Recent advances in semen preservation.

While the horizons for cryobiology may be bright and granted, tremendous strides have been made in the area of artifical insemination(AI), it is evident that only dairy cattle AI with frozen semen has achieved industrial application. Beef cattle AI has been hampered by the lack of suitable techniques for oestrous control. However, with the advent of prostaglandin F2alpha, it may now be possible to make the genetic progress which has been accomplished through AI in dairy cattle. Genetic progress through AI is possible in all far species but the overriding influence has to be economic...

Animals↗
PubMed1984

High density lipoprotein and diabetes mellitus.

The serum HDL2-C, HDL3-C, apo AI and apo AII levels were measured in the non-insulin-dependent diabetic subjects (NIDD) and normal subjects to study the metabolism of HDL in the diabetics. The serum HDL2-C levels in the insulin-treated group were significantly higher than those in the normal group in which the total cholesterol (TC), triglyceride (TG), obesity index and age were matched whereas there was no difference between the serum HDL2-C levels in the oral agent-treated group or group treated by diet only and those in the normal group. These suggest that insulin increases the HDL2-C levels and the increase of the HDL2-C levels is not directly related to changes in the serum TC and TG levels, obesity index and age. No significant differences in the serum apo AI and apo AII levels were found between the insulin group and normal group. From these results it is suggested that in the insulin group the cholesterol/apoprotein ratio in the HDL2 is higher than that in the normal group. The serum apo AI and apo AII levels were significantly lower in the diabetics with an ischemic heart disease (IHD) than those in the diabetics without the IHD. The results show that in the diabetics the apo AI and apo AII play an important role in preventing the development of IHD.

Adult↗
PubMed1983

Studies in antifertility agents--Part XLI : Secosteroids--X : Syntheses of various stereoisomers of (+/-) 2,6 beta -diethyl-7 alpha -ethynyl-3-(p-hydroxyphenyl)-trans-bicyclo[4.3.0]nonan-7 beta-ol.

The syntheses of (+/-) 2 alpha,6 beta -diethyl-7 alpha -ethynyl-3 alpha-(p-hydroxyphenyl)-trans- bicyclo[4.3.0]nonan-7 beta-ol (8), (+/-)2 beta,6 beta-diethyl-7 alpha-ethynyl-3 beta-(p-methoxy-phenyl)-trans-bicyclo[4.3.0]nonan-7 beta-ol 12 and (+/-) 2 alpha,6 beta-diethyl-7 alpha-ethynyl-3 beta-(p-hydroxyphenyl)- trans-bicyclo[4.3.0]nonan-7 beta-ol (18) and their derivatives, which are essentially B-seco-steroids having cis-anti-trans, cis-syn-trans and trans-anti-trans geometries have been carried out. A study of their antiimplantation activities (AI) and receptor binding affinities (RBA) show that trans-anti-trans compounds are biologically most potent, followed by the corresponding cis-anti-trans and cis-syn-trans compounds. The most potent compound 18 is active at 1 mg/kg in rats. Introduction of 7 alpha-ethynyl group increases their AI activity; however, no significant effect on their RBA is observed.

Animals↗
PubMed1998

Clinical failure of CMV retinitis with intravitreal cidofovir is associated with antiviral resistance.

OBJECTIVES: To determine the incidence of clinical resistance to intraocular cidofovir injection for treatment of acquired immunodeficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis, and to identify virologic features associated with cidofovir treatment failure. PATIENTS AND METHODS: Clinical resistance to intravitreal cidofovir was examined in 64 patients with CMV retinitis who received at least 1 injection of 20 pg of cidofovir. Histopathologic examination, culture, and polymerase chain reaction were used to detect CMV in ocular specimens. Antiviral resistance was assessed by plaque reduction assay and DNA sequencing. RESULTS: Clinical resistance to intravitreal cidofovir injections was identified in 3 patients (5%) and was associated with prior oral ganciclovir or intravenous cidofovir use. Ganciclovir- and cidofovir-resistant CMV isolates were cultured from 2 patients and harbored resistance-associated mutations in the UL97 and polymerase genes. Resistance mutations were also detected by direct analysis of vitreous. In 1 patient, different resistance mutations were identified in ocular vs extraocular CMV strains. CONCLUSIONS: Clinical failure of intravitreal cidofovir occurs infrequently, but may be associated with cidofovir-resistant CMV selected by prior ganciclovir or cidofovir treatment. Ocular CMV disease can result from a localized infection with a resistant CMV strain, and antiviral resistance may develop at a local site of infection independently from resistance that develops systemically.

AIDS-Related Opportunistic Infections↗
PubMed1999

MPTP-Induced pallidal lesions in rhesus monkeys.

Dopamine neurons in the substantia nigra of the midbrain are the primary neuronal population affected by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) toxicity, which produces the pathological and behavioral features of Parkinson's disease in nonhuman primates and man. We have identified another injury site in magnetic resonance imaging (MRI) brain scans in 13 of 37 rhesus monkeys taken 10-12 months after administration of this neurotoxin via the right carotid artery. Focal lesions, ranging in volume from 6.75 to 60 mm3 in the rostral globus pallidus region, were seen on the right side of the brain in these 13 animals in addition to the midbrain effects. While no significant differences were seen between globus pallidus lesioned and nonlesioned animals in the severity of MPTP-induced parkinsonian symptoms, the response to levodopa was muted in pallidal-lesioned animals. To confirm the role of neurotoxicity in producing the lesions, brain scans from an additional 12 monkeys were evaluated during the acute period following exposure to either MPTP (n = 6) or saline (n = 6). Focal lesions in the rostral globus pallidus were seen as early as 2-4 h following a carotid artery infusion in two of six MPTP recipients, but no evidence of injury was seen in saline recipients. The globus pallidus includes important components of the neural circuitry regulating motor functions. The present results indicate that in addition to midbrain dopamine neurons, a focal region of the rostral globus pallidus is selectively vulnerable to MPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2025

Insights into dill (Anethum graveolens) flavor formation via integrative analysis of chromosomal-scale genome, metabolome and transcriptome.

INTRODUCTION: Dill (Anethum graveolens) is a significant medicinal herb belonging to the Apiaceae family. Owing to its high levels of volatile organic compounds (VOCs), dill is commonly utilized for essential oil extraction and medicine purpose. However, the biosynthesis of the crucial VOC in dill remains obscure. OBJECTIVES: Identify the key VOCs related to the flavor formation in dill and dissect the regulatory mechanism of their synthesis. METHODS: The dill chromosomal-level genome was constructed by PacBio HiFi, Hi-C, and BGISEQ second generation sequencing and assembly. The VOCs in dill leaves were identified through GC-MS. The potential mechanism involved in regulating the VOC accumulation in dill flavor formation was analyzed by multi-omics analysis. RESULTS: A 1.17&#xa0;Gb chromosome-scale genome of dill with a contig N50 of 10.78&#xa0;Mb was constructed. A total of 46,538 genes were annotated across 11 assembled chromosomes. Comparative genomics analysis suggested that transposable element insertions, especially LTR-Gypsy, have contributed to the evolution and expansion of the dill genome. The flavor formation of dill was mainly attributed to terpenoids, especially &#x3b1;-phellandrene, &#x3b2;-ocimene, and o-cymene. The contribution of expansion and replication of terpenoid synthesis pathway genes, especially terpene synthase (TPS), to the abundant terpenoid production of dill was identified. Differential gene expression patterns observed at various developmental stages and tissues provided key candidate genes for the regulation of terpenoid synthesis, as well as transcription factors. The different accumulation of esters and aromatics also affected the flavor formation of dill. The key genes implicated in the synthesis of anethole, namely AIS and AMT were further identified. CONCLUSION: This study constructed the chromosome level genome and identified the main VOCs and related key genes in flavor formation of dill, shedding lights on our understanding of terpenoid biosynthesis but also offered guidance for future genetic research on molecular breeding in Anethum graveolens.

Transcriptome↗
PubMed2003

Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines.

Hypermethylation of CpG islands in the promoter regions is an important mechanism to silence the expression of many important genes in cancer. The hypermethylation status is passed to the daughter cells through the methylation of the newly synthesized DNA strand by 5-cytosine DNA methyltransferase (DNMT). We report herein that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol from green tea, can inhibit DNMT activity and reactivate methylation-silenced genes in cancer cells. With nuclear extracts as the enzyme source and polydeoxyinosine-deoxycytosine as the substrate, EGCG dose-dependently inhibited DNMT activity, showing competitive inhibition with a K(i) of 6.89 microM. Studies with structural analogues of EGCG suggest the importance of D and B ring structures in the inhibitory activity. Molecular modeling studies also support this conclusion, and suggest that EGCG can form hydrogen bonds with Pro(1223), Glu(1265), Cys(1225), Ser(1229), and Arg(1309) in the catalytic pocket of DNMT. Treatment of human esophageal cancer KYSE 510 cells with 5-50 microM of EGCG for 12-144 h caused a concentration- and time-dependent reversal of hypermethylation of p16(INK4a), retinoic acid receptor beta (RARbeta), O(6)-methylguanine methyltransferase (MGMT), and human mutL homologue 1 (hMLH1) genes as determined by the appearance of the unmethylation-specific bands in PCR. This was accompanied by the expression of mRNA of these genes as determined by reverse transcription-PCR. The re-expression of RARbeta and hMLH1 proteins by EGCG was demonstrated by Western blot. Reactivation of some methylation-silenced genes by EGCG was also demonstrated in human colon cancer HT-29 cells, esophageal cancer KYSE 150 cells, and prostate cancer PC3 cells. The results demonstrate for the first time the inhibition of DNA methylation by a commonly consumed dietary constituent and suggest the potential use of EGCG for the prevention or reversal of related gene-silencing in the prevention of carcinogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed2005

[Effect of ginsenoside on the cellular proliferation, apoptosis and cell cycles in LC A549 and HUVEC 304 cell lines].

OBJECTIVE: To determine the effect of ginsenoside on the cellular proliferation, apoptosis and cell cycles in LC A549 and HUVEC 304 cell lines. METHODS: A549 and HUVEC 304 cell lines were cultured with different concentrations of ginsenoside. Cellular proliferation was detected with MTT, apoptosis and cell cycles were checked with Flow Cytometer, and change of microstructure was observed by transmission electron microscope. RESULTS: The apoptosis rate was 29.8% in A549 cell lines after being interfered with ginsenoside at 3 x 10(-6) mol/L, significantly higher than that in the control group ( P < 0.05). No change was observed in the cell cycles after being interfered with ginsenoside. The inhibitive rate of ginsenoside was 12.53% for HUVEC 304 cell line at 1 x 10(-4) mol/L (P < 0.05 ). The cells induced by conditioned medium could be inhibited by ginsenoside, and apoptotic body could be found in cells induced by conditioned medium at 10(-6) mol/L. CONCLUSION: The proliferation of vascular endothelial cell could be inhibited by ginsenoside, and apoptosis could also be found in both tumor cells and cells induced by conditioned medium after being interfered with ginsenoside.

Adenocarcinoma↗
PubMed2002

The growth response of Escherichia coli to neurotransmitters and related catecholamine drugs requires a functional enterobactin biosynthesis and uptake system.

The neurotransmitter norepinephrine (NE) stimulates the growth of low inocula of Escherichia coli in a minimal medium (SAPI) supplemented with serum (SAPI+serum) and induces the production of an "autoinducer" (AI) which, in turn, promotes E. coli growth in the absence of NE. Given the importance of NE, epinephrine, and their corresponding adrenergic agonists and antagonists in clinical medicine, we sought to investigate the molecular basis for these observations. Using a variety of NE precursors, metabolites, and therapeutic agents, we demonstrated that their ability to stimulate E. coli growth in SAPI+serum is dependent on the presence of a catechol (1,2-dihydroxybenzene) moiety with maximal activity requiring a two-carbon substituent incorporating a terminal primary amine. Serum contains the iron-binding glycoprotein, transferrin, and when SAPI+serum was supplemented with sufficient Fe(3+) to saturate transferrin, growth inhibition was relieved. Other metal cations, including Mg(2+), Ca(2+), and Zn(2+), had no effect. These data suggested that the stimulation of E. coli growth by NE in SAPI+serum may involve the catecholate siderophore, enterobactin, a cyclic triester of 2,3-dihydroxybenzoylserine. Consistent with this hypothesis, E. coli strains with mutations in ferrienterobactin transport (fepA or tonB) or enterobactin biosynthesis (entA) did not respond to NE. Furthermore, NE induced expression of the ferrienterobactin receptor, FepA, during growth in SAPI+serum. The enterobactin degradation product, 2,3-dihydroxybenzoylserine (DBS) was as effective as NE in stimulating the growth of E. coli and mutations in fepA or tonB abolished the DBS-dependent growth stimulation. In contrast to NE, however, DBS stimulated the growth of the entA mutant. Moreover, after growth in an iron-limited M9 medium in the absence of NE, ethyl acetate extracts of the E. coli entA(+) parent but not of the entA mutant contained AI, i.e., stimulated the growth of E. coli in SAPI+serum. Taken together, these data show that when low numbers of E. coli are inoculated into SAPI+serum, NE, DBS, and related catecholamines induce the enterobactin iron uptake system. This, in turn, facilitates iron sequestration from transferrin and indicates that the AI present in NE-conditioned SAPI+serum medium is enterobactin and its DBS breakdown products.

Catecholamines↗