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 595 records · Page 33Linked to original sources
PubMed2025

The application of AI-driven and engineered intratumoral microbes in cancer therapy.

BACKGROUND: Although investigations of the intratumoral microbiota date back thousands of years, breakthrough transformations have only recently been achieved through high-throughput sequencing and multiomic technologies. These advances have revealed diverse and tumor type-specific microbial communities that drive carcinogenesis via immunomodulation, metabolic reprogramming, and genomic instability. Current cornerstones of cancer therapies-including chemotherapy, radiotherapy, immunotherapy, and targeted therapy-are limited by systemic toxicity, localized tissue damage, drug resistance, and low patient response rates. These constraints underscore the urgent need for more effective and precise therapeutic strategies. MAIN BODY: This review comprehensively integrates artificial intelligence (AI) technologies into the characterization of the intratumoral microbiota, facilitating the development of novel computational pipelines for mapping microbe-host crosstalk. We systematically summarize recent advances in engineered microbial therapeutics, including bacteria designed for targeted antitumor activity and engineered microorganisms that enable the localized delivery of therapeutic agents. Furthermore, this review critically evaluates the safety profiles of microbiota-based interventions and discusses key challenges in clinical translation. CONCLUSIONS: By combining cutting-edge computational technologies, biological research, and clinical insights, this review aims to bridge the gap between microbiome science and oncological practice, pioneering innovative strategies for microbiota-guided diagnostics and personalized cancer therapy.

Humans↗
PubMed2003

Blockade of paeoniflorin on sodium current in mouse hippocampal CA1 neurons.

AIM: To study the blockade of paeoniflorin (Pae) on I(Na) in the acutely isolated hippocampus neurons of mice. METHODS: The whole-cell patch clamp technique was used. RESULTS: Pae inhibited I(Na) in frequency-dependent and concentration-dependent manners, with an IC50 of 271 micromol/L. Pae 0.3 mmol/L shifted the activation potential of the maximal I(Na) from -40 mV to -30 mV, shifted the steady-state activation and inactivation curves toward more positive and negative potentials by 10.8 mV, and 18.2 mV, respectively, and postponed the recovery of I(Na) inactivation state from (4.2+/-0.7) ms to (9.8+/-1.2) ms. CONCLUSION: Pae inhibited I(Na) in mouse hippocampus neurons.

Animals↗
PubMed2006

Action of beta-amyloid peptide₁₋₄₀ on I(HVA) and its modulation by ginkgolide B.

Whole-cell patch clamp recording was used to investigate the action of beta-amyloid peptide(1-40) (Abeta(1-40)) on high voltage-activated calcium channel current (I(HVA)) in acutely isolated hippocampal CA1 pyramidal neurons in rats and observe its modulation by ginkgolide B (GB). Drug was applied by extracellular bath or adding in the pipette solution, and its effect was determined by comparing the amplitude of I(HVA) before and after the drug application. Bath application of aggregated Abeta(1-40) at concentrations of 0.01~30 mumol/L increased the amplitude of I(HVA) in a dose-dependent manner by (5.43+/-3.01)% (n=8, P>0.05), (10.49+/-4.13) % (n=11, P>0.05), (40.69+/-8.01) % (n=16, P<0.01), (58.32+/-4.85) % (n=12, P<0.01), and (75.45+/-5.81) % (n=6, P<0.01), respectively, but had no effect on the I-V curve of I(HVA); fresh Abeta(1-40) almost had no effect on I(HVA) (n=5, P>0.05). L-type calcium channel antagonist nifedipine abolished the increase of I(HVA)by Abeta(1-40). The increase of I(HVA) by Abeta(1-40) (1.0 mumol/L) was enhanced to (66.19+/-5.74) % (P<0.05) by 8-Br-cAMP (membrane permeable analogue of cAMP) and to (73.21+/-6.90) % (P<0.05) by forskolin, an adenylyl cyclase (AC) agonist, and reduced to (20.08+/-2.18) % (P<0.05) by H-89, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) antagonist. GB effectively inhibited the increase of I(HVA) by Abeta(1-40). The results indicate that Abeta(1-40) leads to an intracellular calcium overload by increasing I(HVA) via AC-cAMP-PKA. This may be one of the mechanisms for its neurotoxicity. GB can prevent neurons from neurotoxicity by inhibiting abnormal calcium influx caused by Abeta(1-40).

Amyloid beta-Peptides↗
PubMed1993

[Qing-shen tiao-zhi tablet in the treatment of hyperlipemia in the middle and old aged].

The effect of Qing-Shen Tiao-Zhi (QSTZ) tablet which consisted of Rheum palmatum and Alismatis orientale etc. on serum TC, TG, HDL-C, LDL-C and atherogenic index (AI) was reported in 73 senile hyperlipemic patient, while another 21 patients took Yue Jian Cao (YJC) oil capsule. The results showed that total effective rate was 91.7% in QSTZ group, and 71.43% in the YJC group (P < 0.05). The levels of TC, TG and LDL-C before and after medication showed significant difference, P < 0.01 in QSTZ group and that there was only a few persons those P < 0.05 in control group. About AI, it revealed in QSTZ and control group as P < 0.01 and > 0.05 respectively.

Aged↗
PubMed2004

The effect of embryonic death rates in cattle on the efficacy of estrus synchronization programs.

Reproductive failure in inseminated cattle results from poor fertilization and embryo survival. Recent studies utilizing dairy and beef cattle indicate that fertilization rates are higher for nulliparous dairy and beef heifers and nonlactating beef cows than lactating beef and dairy cows and nonlactating dairy cows. Several factors affect fertilization rates, but the greatest impact was observed for high producing cows under heat stress, when fertilization was only 55%. Once fertilization has occurred, the fate of a successful pregnancy is then determined by the survival of the embryo and fetus. Losses of pregnancy are characterized by early embryonic death, which occurs prior to the period of corpus luteum (CL) maintenance in the cow at days 15-17 of the cycle, and late embryonic death, which occurs from CL maintenance to the end of the differentiation stage, at approximately 42 days of gestation. After 50 days of gestation, pregnancy losses are less frequent and characterize fetal death. Most pregnancy losses occur prior to the period of maintenance of the CL, but in high producing lactating dairy cattle, substantial losses continue to occur up to 42-56 days after insemination. Several factors affect pregnancy losses in cattle, such as compromised oocytes, which result in poorly developed embryos incapable of cross-talking with the endometrial epithelial cells, to inadequate uterine environment and infectious agents resulting in death of the embryo from undernourishment. Recently, studies have indicated that anovulation/anestrous, the metabolic status of the animal, some dietary ingredients, as well as occurrence of diseases, predispose the cow to experience embryonic and fetal death. Although some insemination protocols might impact embryo survival, when timed AI has been implemented properly, it has not influenced embryonic or fetal death in cattle. Improvements in reproductive programs in the future will have to focus on enhancing fertilization rates and minimizing embryonic losses to optimize conception rates in dairy and beef cattle.

Animal Nutritional Physiological Phenomena↗
PubMed2006

Association of XRCC1 gene polymorphisms with the susceptibility and chromosomal aberration of testicular germ cell tumors.

It is known that many genomic and genetic alterations caused by aging or environmental factors are responsible for cancer development and progression. XRCC1 is involved in the repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. The objective of this study was to investigate the association of genomic alterations and the susceptibility of testicular germ cell tumors with XRCC1 polymorphisms. Two polymorphisms of XRCC1, Arg194Trp and Arg399Gln, were genotyped in 83 patients with testicular germ cell tumors (TGCT) and 87 male controls. Allelic imbalances (AI) were evaluated using 4 microsatellite markers in a subgroup of 50 patients. Patients with at least one Gln allele of the Arg399Gln polymorphism had an increased risk of TGCT than those with the Arg/Arg genotype (aOR=1.775, 95% CI=1.045-3.016, P=0.034). Furthermore, the increased risk associated with the Gln allele against the Arg homozygote was more strongly observed in patients with pure seminoma (aOR=2.242, 95% CI=1.149-4.374, P=0.018) or with metastasis (aOR=2.481, 95% CI=1.267-4.862, P=0.008). In the Arg194Trp polymorphism, there was no significant difference in the genotype distribution between TGCT patients and the controls. In AI analysis, the frequency of AI was significantly higher in tumors with at least one Gln allele than those with the Arg/Arg genotype in D13S317 (P=0.010) and in a combination of 4 markers (0.51+/-0.32 vs 0.32+/-28, P=0.028). Our results suggest that the Gln allele of the XRCC1 Arg399Gln polymorphism may genetically modify the development and progression of TGCT through genomic instability.

Chromosome Aberrations↗
PubMed2007

Aromatase inhibitors and cardiac toxicity: getting to the heart of the matter.

Recent advances in breast cancer treatment include the advent of aromatase inhibitors (AIs) in the adjuvant setting with better efficacy and toxicity profiles than tamoxifen. However, AIs generally do not improve lipid profile as tamoxifen does, and there has been suggestion of increased cardiovascular risk with AI use. This has become an area of concern, particularly in light of the view that tamoxifen may protect against cardiovascular disease. This review of the current literature and updated trial data examines the effect both AIs and tamoxifen have on lipids and cardiovascular risk. It also highlights the importance of interpreting such data within the larger context of cardiovascular health in postmenopausal women.

Antineoplastic Agents, Hormonal↗
PubMed2005

Autoinducer 2-like activity in poultry-associated enteric bacteria in response to subtherapeutic antibiotic exposure.

The autoinducer-2 molecule, AI-2, is considered to be a universal signal for regulating a wide variety of physiological processes in bacteria by modulating gene expression. Studies were conducted to observe how Escherichia coli cells would respond to subtherapeutic tetracycline concentrations under continuous culture (chemostat) conditions, to observe AI-2 activity within the probiotic chicken microbial consortium (Preempt CF3; MS Bioscience, Dundee, IL) under in vitro conditions simulating a chicken cecum, and to observe the AI-2 activity in vivo within a chicken cecum as a function of exposure to subtherapeutic levels of chlortetracydine, tylosin, and vancomycin. The AI-2 activity in the E. coli continuous culture showed a 20-fold increase over baseline conditions for up to 24 hours. When the E. coli culture was subsequently exposed to pulses of chlortetracydine additions at subtherapeutic concentrations (2 microg/ml), AI-2 activity increased with increasing levels of tetracycline additions. The probiotic Preempt CF3 culture, however, did not exhibit any AI-2 activity in Viande Levure (VL) medium in the presence or absence of subtherapeutic levels of tetracycline. In vivo studies in the cecum of poultry chicks demonstrate that though AI-2 activity increased initially in the presence of vancomycin, there was no significant increase in AI-2 activity in the presence of tetracydine or tylosin. These results indicate that detectable levels of AI-2 activity are not evident within the probiotic culture (CF3) or within the chicken cecum. Understanding the relationships between AI-2 activity and microbial consortia characteristics could provide dues regarding the vulnerability of poultry chicks to enteric bacterial pathogen colonization.

Animals↗
PubMed2003

A selective angiotensin receptor antagonist, Valsartan, produced regression of left ventricular hypertrophy associated with a reduction of arterial stiffness.

We investigated whether a selective angiotensin II receptor blocker (ARB) would have a regressive effect on left ventricular hypertrophy (LVH) in patients on continuous ambulatory peritoneal dialysis (CAPD). In a double-blind study, 24 CAPD patients with LVH [left ventricular mass index (LVMi) > 110 g/m2 for women and LVMi > 137 g/m2 for men] were randomized to 12 months' administration of either the ARB valsartan (n = 14) or a placebo (n = 10). The target blood pressure (BP) was 140/90 mmHg or lower in both groups. The following parameters were measured before and at the end of the study: aortic and large-artery compliance and arterial wave reflections [pulse wave velocity (PWV) and augmentation index (AI) application tonometry] and cardiac echocardiography. Periodically recorded were body weight, BP (mercury sphygmomanometer), serum creatinine, electrolytes, complete blood cell counts, urine volume, drainage volume, and weekly creatinine clearance. Two-way analysis of variance for repeated measurements was used for statistical analysis. Systolic and diastolic BP were both reduced in patients treated with ARB. The LVMi was significantly reduced in patients treated with ARB (to 121 +/- 4 from 145 +/- 5) but not in those receiving placebo (to 137 +/- 3 from 152 +/- 3, p < 0.05). The decrease in LVMi was associated with a reduction in PWV and AI. In CAPD patients with LVH, ARB reduced LVMi in association with alterations in arterial hemodynamics.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Changing the gold standard in adjuvant therapy for breast cancer:from tamoxifen to aromatase inhibition.

The introduction of third generation aromatase inhibitors [anastrozole, letrozole, and exemestane] has certainly improved outcomes inpatients with early breast cancer. Although survival benefit has not been identified (except in the subpopulation of patients with lymph node positive breast cancer on the MA 17 study), the primary endpoints in all studies reached statistical significance in favor of AI. The strategy can include: replacing TAM outright after diagnosis; switching from TAM to one of the aromatase inhibitors after 2-3 years; or to add an AI after 5 years of TAM. DFS, recurrence, and the incidence of contra lateral breast cancer is influenced favorably with such an approach. The following issues remained unanswered: Will the OS be improved as well? Is the incidence of serious long-term side effects acceptable to our patients [osteoporosis, fractures, cognitive function and lipid profile changes]? What is the influence of chemotherapy on the effect of aromatase inhibitors? We still do not know the true role of AI in HER2 positive disease. Which effect do AI have in pre-menopausal women(with the use of LHRH agonists)? How long should patients after TAM be receiving AI? Several of these questions will be certainly answered with the new generation of studies, but many of these questions have just been generated with these new results.

Anastrozole↗
PubMedDate not supplied

[Comparative evaluation of the hypoglycemic activity of the vegetal complex of Phaseolus vulgaris and chlorpropamide in experimental diabetes].

Experiments on rabbits with alloxan diabetes showed that the plant complex (PC) reduced the level of glycemia after single administration for 6-8 h by 27-32%. A similar effect was demonstrated with chlorpropamide. However the PC produced a longer hypoglycemic effect. In course treatment the PC returned the blood level of glucose (5.14 +/- 0.62 mmol/l) to normal on the 11th day whereas with chlorpropamide this indicator was almost normal (6.6 +/- 1.1 mmol/l) on the 15th day only. A rapid decrease in the blood glucose concentration caused by the PC was observed in AIS induced hyperglycemia. The PC demonstrated its sugar reducing action by extrapancreatic means.

Alloxan↗
PubMed1993

A multicentre comparative study of serum lipids and apolipoproteins in long-term users of DMPA and a control group of IUD users. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation Special Programme of Research, Development and Research Training in Human Reproduction.

A clinical trial was conducted in three centres to assess the effects of long-term use of the injectable contraceptive depot-medroxyprogesterone acetate (DMPA) on lipid metabolism. Fifty women who had used DMPA at a dose of 150 mg every three months for 3 to 9 years were recruited in Bangkok, Christchurch and Mexico City. They were compared to a control group of 120 IUD users. Total cholesterol, LDL-cholesterol, HDL-cholesterol, total triglycerides, apolipoproteins AI, AII and B were measured throughout one injection interval. Significant findings differed between centres. Compared to their own centre controls, DMPA users in Bangkok had higher LDL-cholesterol levels; those in Christchurch had lower HDL-cholesterol, apolipoprotein (apo) AI and apo AI/B ratio and higher apo B levels; those in Mexico City had a lower apo AI/B ratio. Further changes were observed during the injection interval, some of which were correlated to changes in serum MPA levels. It is concluded that long-term use of DMPA induces moderate changes in lipid metabolism which are unfavourable in terms of risk for atherosclerosis. This should be borne in mind when weighing the overall risks and benefits of this contraceptive method for a potential user.

Adult↗
PubMed2002

Isolation and characterization of a full-length resistance gene homolog from soybean.

Using mixed resistance gene analogs as probes, a putative resistance gene (KR1) was isolated from soybean and characterized further. The KR1 protein consists of a Toll/interleukin receptor (TIR) domain, a nucleotide binding site (NBS) domain, an imperfect leucine-rich repeat (LRR) domain and two C-terminal transmembrane segments. Due to these features, KR1 represents a distinct member in the TIR-NBS-LRR class of resistance genes. Southern-blot analysis indicated that there were several KR1-related sequences within the soybean genome, and two polymorphic loci were mapped onto linkage group L. KR1 was induced by SA treatment and soybean mosaic virus (SMV) infection in the resistant line (Kefeng 1). An orthologue (NR1) and a homologue (NR2) of the KR1 gene were also identified in the SMV susceptible-line Nannong1138-2. Sequencing analysis revealed that NR2 was highly homologous to KR1 and NR1, but had a 21-bp deletion. Moreover, the NR1, NR2 transcription and the ratio of NR1/ NR2 was up-regulated by viral infection in Nannong1138-2. These results indicated the complexity of the regulatory mechanism in the plant responses to SMV infection.

Amino Acid Sequence↗
PubMed1993

Effects of pravastatin on apolipoprotein-specific high density lipoprotein subpopulations and low density lipoprotein subclass phenotypes in patients with primary hypercholesterolemia.

UNLABELLED: The HMG-CoA reductase inhibitor class of cholesterol-lowering agents reduces very low density lipoproteins (VLDL) and low density lipoproteins (LDL) and slightly increases high density lipoproteins (HDL). However, the effects of these agents on subclasses within the LDL and HDL fractions are not well understood. We have employed an HMG-CoA reductase inhibitor, pravastatin, to determine if LDL subclass phenotypes, as determined by gradient gel electrophoresis, and HDL particles containing both apolipoprotein (apo) A-I and A-II, Lp(AI w AII), and those containing apo A-I but not A-II, Lp(AI w/o AII) are affected by pravastatin (10 mg daily). Twenty-four subjects with LDL-cholesterol (LDL-C) > 160 mg/dl, triglyceride (TG) < 350 mg/dl and no recent myocardial infarction or secondary causes of hypercholesterolemia were enrolled. Compared with an age- and sex-matched normolipidemic reference group (controls), the hypercholesterolemic subjects had reduced levels of Lp(AI w/o AII) and increased levels of Lp(AI w AII) at baseline. In addition, both of their HDL subpopulations had significantly more small (7.0-8.2 nm) particles (P < 0.02 and 0.0001) but significantly fewer large (9.2-11.2 nm) particles (P < 0.002 and 0.0001). Pravastatin induced statistically significant (P < 0.001) reductions in plasma total C (15%), LDL-C (18%), and apo B (16%). While apo A-I and A-II levels increased 5% (P < 0.001) and 6% (P < 0.05), respectively, concentration, composition, and size abnormalities in Lp(AI w AII) and Lp(AI w/o AII) persisted. Lp(a), apo E and cholesteryl ester transfer protein (CETP) levels also did not change. Although changes in LDL subclass phenotypes were observed, all changes involved the intermediate phenotype, and no significant changes in LDL peak particle diameter were seen in either group. Interrelationships between CETP, LDL subclass phenotypes and HDL subpopulations were also seen. CONCLUSIONS: Although pravastatin decreased plasma apo B and LDL lipid concentrations, no major changes were seen in LDL subclass phenotypes or HDL subpopulations even in the presence of abnormalities associated with arteriosclerosis. Similarly, CETP, which is believed to play a role in HDL and LDL particle size distribution, did not change with pravastatin treatment. Further research is needed to determine the pathophysiological basis of abnormal HDL and LDL subclasses in hypercholesterolemia and explore methods of rectifying the abnormalities.

Adult↗
PubMed2004

In vitro growth, acidogenicity and cariogenicity of predominant human root caries flora.

Streptococcus mutans (Sm), Lactobacillus acidophilus (La) and Actinomyces israelii (Ai) have been associated with root surface caries, which is an increasing problem in elderly Chinese. The aim of this study therefore, was to evaluate in vitro, the growth, acidogenicity and cariogenicity of these organisms, both in mono- and co-cultures using an in vitro model. Forty-eight root specimens were prepared using intact extracted human molars. Fresh, wild-type bacteria obtained from root caries lesions were assembled into seven experimental groups as either mono- or co-cultures and incubated with the root specimens. Appropriate controls were included. Growth curve of each experimental group was monitored for 24h, aerobically, at 37 degrees C using a microplate reader. The pH of the medium was recorded after 24-h incubation using a pH meter. Mean depths of artificial root lesions produced in each cultural group were measured using polarized light microscopy in specimens cut into thin sections (100+/-20 microm). Compared with mono-cultures, synergistic growth was observed in co-cultures of 'La+Sm', 'Ai+La' and 'Ai+La+Sm'. Mean lesion depth produced in La group was significantly shallower than other mono- or co-culture groups (p<0.01). The pH values of all culture media were similar after 24-h incubation. The current data elucidate the complex interactions of three predominant bacterial species considered prime agents of human root surface caries.

Acids↗
PubMed2006

The effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers.

Ropinirole is a nonergoline dopamine D(2)-receptor agonist and has been proven to be effective in both monotherapy and combination therapy for idiopathic Parkinson's disease. The purpose of the present study was to examine the effect of Madopar on the pharmacokinetics of ropinirole in healthy Chinese volunteers by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). A single dose of 1mg ropinirole was given orally after administration of the placebo or Madopar (containing 200 mg levodopa and 50 mg benserazide) to six healthy males and six healthy females in a cross-over randomized study with a minimum washout period of 8 days. Pharmacokinetic parameters were calculated for both treatments. Coadministration of ropinirole and Madopar did not result in a notable change in rate or extent of availability of ropinirole, as shown by the ratios (90% confidence intervals) of 1.045 (0.900, 1.222) for C(max) (maximum plasma concentration) and 1.167 (1.086, 1.262) for AUC(0-inf) (the area under the concentration-time curve). Likewise, no significant difference in any of the other pharmacokinetic parameters [T(max) (the time needed to reach the C(max)), MRT (mean residence time), volume of distribution (V/F), and clearance (CL/F)] was observed between the treatment groups. No clinically relevant adverse effects were detected under either conditions and there are no pharmacokinetic grounds for adjusting the dose of ropinirole when given in combination with Madopar in Chinese patients.

Adult↗
PubMed2005

Dopamine D4 receptor gene exon III polymorphism and interindividual variation in response to clozapine.

To investigate the relationship between 48 bp variant number tandem repeat polymorphism in dopamine D4 receptor gene and response to clozapine in schizophrenic patients, the authors included 81 inpatients with a DSM-IV diagnosis of schizophrenia and patients meeting criteria for refractory to treatment were excluded. This study found that the frequencies of five 48 bp repeats homozygous genotype and five 48 bp repeats allele were significantly less in the responders than the nonresponders, which divided by improving total schizophrenic symptom. The results of this study suggest that inherited variants of D4 may explain some of the interindividual variation seen in patient response to clozapine.

Adult↗