Longevity extension in rats via improved redox homeostasis with high carbohydrate diet intervention from weaning to adulthood: a comprehensive multi-omics study.

Early dietary patterns potentially influence the health status and lifespan throughout adulthood and the entire lifespan. However, dietary behaviors are difficult for everyone to control during adolescence. It is even more important to study the effects of interventions of early dietary patterns on the lifespan under arbitrary feeding conditions. The research involves observing the survival status and lifespan of rats from weaning to adulthood with three different dietary patterns (a high-carbohydrate diet (HC), a high-protein diet (HP), and a high-fat diet (HF)) under ad libitum feeding conditions. The administration of high-carbohydrate diets leads to a significant extension of both median and maximum survival times (P < 0.05) in Wistar rats. Furthermore, it markedly enhanced the spatial memory capacity, mitigated the occurrence of liver and kidney pathological outcomes in elderly rats, and increased the abundance of gut microbiota improving amino acid metabolism. Additionally, feeding rats a high-carbohydrate diet improved glutathione (GSH) synthesis and recycling and activated the expression and upregulation of the lifespan-related proteins Foxo3a/Sirt3 and the key metabolic enzyme GPX-4. The high-carbohydrate diet from weaning to adulthood may potentially extend the lifespan by enhancing rat systemic glutathione synthesis, recycling, and improving the redox state pathway.

A prediction model based on digital breast pathology image information.

BACKGROUND: The workload of breast cancer pathological diagnosis is very heavy. The purpose of this study is to establish a nomogram model based on pathological images to predict the benign and malignant nature of breast diseases and to validate its predictive performance. METHODS: In retrospect, a total of 2,723 H&E-stained pathological images were collected from 1,474 patients at Qingdao Central Hospital between 2019 and 2022. The dataset consisted of 509 benign tumor images (adenosis and fibroadenoma) and 2,214 malignant tumor images (infiltrating ductal carcinoma). The images were divided into a training set (1,907) and a validation set (816). Python3.7 was used to extract the values of the R channel, G channel, B channel, and one-dimensional information entropy from all images. Multivariable logistic regression was used to select variables and establish the breast tissue pathological image prediction model. RESULTS: The R channel value, B channel value, and one-dimensional information entropy of the images were identified as independent predictive factors for the classification of benign and malignant pathological images (P < 0.05). The area under the curve (AUC) of the nomogram model in the training set was 0.889 (95% CI: 0.869, 0.909), and the AUC in the validation set was 0.838 (95% CI: 0.7980.877). The calibration curve results showed that the calibration curve of this nomogram model was close to the ideal curve. The decision curve results indicated that the predictive model curve had a high value for auxiliary diagnosis. CONCLUSION: The nomogram model for the prediction of benign and malignant breast diseases based on pathological images demonstrates good predictive performance. This model can assist in the diagnosis of breast tissue pathological images.

Cardiovascular profile of contemporary treatments of renal cell carcinoma: A single-center prospective study.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). Emerging data suggest that these agents can result in clinically significant cardiotoxicity, compromising the care. METHODS: We conducted a prospective longitudinal study to evaluate the incidence of de novo cardiac dysfunction as assessed by echocardiography and blood biomarkers in mRCC patients receiving TKI with or without ICI followed at baseline, 3-month and 6-month. We recruited consecutive newly diagnosed mRCC patients treated at our institution between 2015 and 2018 as well as patients with localized RCC not treated with systemic therapies and healthy control (HC) subjects for comparison. RESULTS: Twenty-eight patients were enrolled in the mRCC group (a mean age of 65.2 ± 7.5 years), 29 patients in the localized RCC group (63.6 ± 8.9 years), and 20 volunteers in the HC group (52.9 ± 9.6 years). At baseline, patients from all three groups had normal cardiac function as measured by left ventricular ejection fraction (LVEF), although patients with mRCC or localized RCC had significantly lower mean LVEF compared to HC (61.9%, 62.4%, and 68.1% respectively). Otherwise, there were no statistically significant changes in echocardiographic parameters or incidence of clinical heart failure from baseline to 6-months in patients with mRCC. Cardiac blood biomarkers including troponin I, brain natriuretic peptide, and galectin-3 remained stable over time. CONCLUSION: Our findings suggest that contemporary treatment strategies of mRCC at this single institution are well tolerated without clinically meaningful overt declines in cardiac function over time. Further studies are warranted to include a larger number of patients to better assess the overall cardiovascular safety associated with contemporary treatments of mRCC.

Modification of Palladium Nanocrystals with Single Atom Platinum via an Electrochemical Self-Catalysis Strategy for Efficient Formic Acid Electrooxidation.

Single atom alloys (SAA) have recently drawn increased attention due to their unique structure, high atomic utilization, and fascinating catalytic performance. However, their controllable synthesis still presents a challenge. This study proposes an electrochemical self-catalysis (ESC) strategy to synthesize Pd@Pt/C SAA catalysts, that is, depositing Pt atoms on Pd nanocrystals through in situ decomposition of sodium formate. The relationship between composition and structure of Pd@Pt/C is distinguished through a combination of electrochemical analysis, sphere-corrected scanning transmission electron microscopy, and X-ray adsorption spectra. That relationship evolved from SAA to a sea-island structure and even a core-shell structure with composition-controllable atomic ratios, highlighting the great diversity and convenience of this method in nanostructure construction. The Pd@Pt/C SAA catalyst showed excellent catalytic activity to formic acid oxidation with a peak current density of 5.2 A/mgmetal, which is about 18.6 times that of the commercial Pd/C. density functional theory calculations revealed that the enhanced activity was due to the "passivation" of Pd sites near the Pt single atoms, which attenuated the adsorption of CO. Based on electrochemical principles, this ESC strategy was also expanded to prepare a series of Pd-based SAA, including Pd-Au, Pd-Ir, and Pd-Bi.

Ginsenoside Rg2 Ameliorates Brain Injury After Intracerebral Hemorrhage in a Rat Model of Preeclampsia.

The incidence of maternal hemorrhagic stroke is elevated in women with preeclampsia during pregnancy. Panax ginseng is a traditional medicinal herb with numerous applications, and ginsenosides are the key bioactive compounds in Panax ginseng. This study aims to evaluate the effects of ginsenoside Rg2 on pregnancy outcomes and brain injury after intracerebral hemorrhage (ICH) in a rat model of preeclampsia. Preeclampsia was induced in rats by N(ω)-nitro-L-arginine methyl ester. Then, an ICH model was prepared by intrastriatal injection of bacterial collagenase. Ginsenoside Rg2 markedly elevated the survival ratio of fetuses. The placental and body weights were increased in the ginsenoside Rg2 group. Compared with the preeclampsia group, the Garcia test score of ginsenoside Rg2-treated rats was significantly increased. Ginsenoside Rg2 treatment ameliorated the ICH-induced augmentation of Evans blue extravasation, inhibited the ICH-induced elevation of brain water content, and reduced the interleukin-1ß and tumor necrosis factor-α levels in the hemorrhagic hemisphere after ICH in preeclampsia model rats. Furthermore, ginsenoside Rg2 treatment not only inhibited augmentation of TLR-4, MyD88, p-IκBα, and p-NF-κB expression but also abated the reduction of occludin and claudin-5 expression in the hemorrhagic hemisphere. The findings indicated that ginsenoside Rg2 improved pregnancy outcomes in a rat model of preeclampsia without decreasing the blood pressure and urine protein level. The findings also demonstrated that ginsenoside Rg2 ameliorated ICH-induced neurological disorder and blood-brain barrier dysfunction in an animal model of preeclampsia by regulating the TLR4/NF-κB signaling pathway.

Association between relational trauma and empathy among male offenders in China.

BACKGROUND: Offenders are more likely than the general population to have experienced relationship trauma. They are also more likely to have lower empathy. To date, relationships between historical trauma and later empathic states have not been examined among offenders. AIMS: To explore the association between history of trauma in close personal relationships and empathy among offenders. Our research question is: Is such relational trauma associated with self-rated impairments in empathy? METHODS: All men with a primary school education and above at a single all-male prison in Jiangsu Province in China were invited to participate. The self-reported Interpersonal Reactivity Index was used to evaluate empathy, and the Brief Betrayal Trauma Survey was to explore interpersonal trauma and classify such experiences. RESULTS: Interpersonal trauma was associated with higher personal distress and lower empathic concern among men reporting relational trauma in adulthood, but only higher personal distress when the trauma reported was in childhood. Non-relational trauma was associated with higher empathic concern. Cognitive aspects of empathy varied little between groups. CONCLUSIONS: Our findings add to the existing literature by making distinctions between the types of trauma and the age of key experience in its relationship to self-reported empathy. The differences found suggest that it may be helpful to consider planning any trauma-related interventions differently according to the type and age of trauma experiences.

Surfactant-Free Synthesis of Three-Dimensional Metallic Nanonetworks via Nanobubble-Assisted Self-Assembly.

Three-dimensional metallic nanonetworks (3D-MNWs) demonstrate unique performances across a wide range of fields, and their facile and green synthetic method is of high significance. Herein, we report a self-generated-nanobubble scaffolding strategy for the fabrication of 3D-MNWs, which employs aqua ammonia (AA) as a nanobubble reservoir and avoids the use of any surfactants or polymeric capping agents. Benefiting from the interaction between ammonia and metallic nanoparticles, finely interlocked nanonetworks (Au, Pt, Ag, and Cu) with curved geometry and abundant pores are obtained by precisely controlling the anisotropic kinetic growth using a strong reducing agent and a high concentration of AA. As a demonstration, the methanol oxidation reaction (MOR) is tested to assess the electrocatalytic performance of the Pt 3D-MNWs. The peak current of Pt 3D-MNWs reaches 152 mA/mgPt, which is 2.5 times higher than that of commercial Pt black. This unique nanobubble-assisted strategy has great potential in the basic synthetic prototype for polyporous nanomaterials.

Atrial Fibrillation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.

PURPOSE: To examine the incidence and risk factors for de novo atrial fibrillation (AF) after allogeneic hematopoietic cell transplantation (HCT) and to describe the impact of AF on HCT-related outcomes. METHODS: A retrospective cohort study design was used to examine AF and associated outcomes in 487 patients who underwent allogeneic HCT from 2014 to 2016 and to characterize patient- and HCT-related risk factors. A nested case-control study design was used to describe the association between pre-HCT echocardiographic measures and future AF events. RESULTS: The median age at HCT was 52.4 years (18.1-78.6); the median time to AF was 117.5 days (4.0-1,405.0). The 5-year cumulative incidence of AF was 10.6%. Older (≥ 50 years) age (hazard ratio [HR], 2.76; 95% CI, 1.37 to 5.58), HLA-unrelated donor (HR, 2.20; 95% CI, 1.18 to 4.12), dyslipidemia (HR, 2.40; 95% CI, 1.23 to 4.68), and pre-HCT prolonged QTc interval (HR, 2.55; 95% CI, 1.38 to 4.72) were independent risk factors for AF. Despite having comparable left ventricular systolic function, patients who developed AF were significantly more likely to have lower left atrial ejection fraction, left atrial reservoir function, and elevated tricuspid regurgitant jet velocity prior to HCT, compared with patients who did not. The incidence rate of stroke after AF was 143 per 1,000 person-years. In adjusted analyses, AF was associated with a 12.8-fold (HR, 12.76; 95% CI, 8.76 to 18.57) risk of all-cause mortality and 15.8-fold (HR, 15.78; 95% CI, 8.70 to 28.62) risk of nonrelapse mortality. CONCLUSION: The burden of AF after allogeneic HCT population is substantial, and the development of AF is associated with poor survival. We identified important associations between patient demographics, pre-HCT cardiac parameters, HCT-related exposures, and risk of AF, setting the stage for targeted prevention strategies during and after HCT.

Exosomes Derived From CircAkap7-Modified Adipose-Derived Mesenchymal Stem Cells Protect Against Cerebral Ischemic Injury.

BACKGROUND: Cerebral ischemic injury is a complicated pathological process. Adipose-derived stromal cells (ADSCs) have been used as a therapeutic strategy, with their therapeutic effects chiefly attributed to paracrine action rather than trans-differentiation. Studies have shown that circAkap7 was found to be downregulated in a mouse model of transient middle cerebral artery occlusion (tMCAO). METHODS: To explore whether exosomes derived from circAkap7-modified ADSCs (exo-circAkap7) have therapeutic effects on cerebral ischemic injury, a mouse model of tMCAO, as well as an in vitro model of oxygen and glucose deprivation-reoxygenation (OGD-R) in primary astrocytes, were used. RESULTS: Results showed that treatment with exo-circAkap7 protected against tMCAO in mice, and in vitro experiments confirmed that co-culture with exo-circAkap7 attenuated OGD-R-induced cellular injury by absorbing miR-155-5p, promoting ATG12-mediated autophagy, and inhibiting NRF2-mediated oxidative stress. CONCLUSION: We demonstrate here that exo-circAkap7 protected against cerebral ischemic injury by promoting autophagy and ameliorating oxidative stress.

Endocarditis following Consumption of Cereal Associated with Salmonella enterica Subtype Mbandaka Outbreak.

A 69-year-old immunocompromised man developed mitral valve endocarditis due to Salmonella enterica serotype Mbandaka, contracted from the cereal outbreak. The patient had a history of HLA-matched related hematopoietic stem cell transplant with persistent graft-versus-host disease (GVHD). This case report discusses prior international outbreaks that occurred due to Salmonella enterica subtype Mbandaka, the risks of developing endovascular infections from salmonellosis, and persistent infections that may develop more frequently with S. enterica serotype Mbandaka. The patient received a six-week course of intravenous antibiotics and remains on oral suppressive antibiotics, with his length of therapy to be determined based on his GVHD treatment.

Exosomes from MiR-30d-5p-ADSCs Reverse Acute Ischemic Stroke-Induced, Autophagy-Mediated Brain Injury by Promoting M2 Microglial/Macrophage Polarization.

BACKGROUND/AIMS: Recent studies have indicated that exosomes secreted from adipose-derived stem cells (ADSCs) have important effects in the treatment of ischemic injury. However, the treatment mechanism is unclear. This study aimed to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-30d-5p have a protective effect on acute ischemic stroke (AIS). METHODS: In the current study, inflammatory factors and miR-30d-5p expression were assessed in 70 subjects with AIS and 35 healthy controls. Exosomes were characterized by transmission electron microscopy and further examined using nanoparticle tracking analyses. A rat model of AIS and an in vitro model of oxygen- and glucose-deprived (OGD) primary microglia were established to study the protective mechanism of exosomes from miR-30d-5p-overexpressing ADSCs in ischemia-induced nerve injury. RESULTS: The results showed that following AIS, the expression of inflammatory cytokines increased, while the anti-inflammatory cytokines IL-4, IL-10, and miR-30d-5p decreased both in patients and in animal models. Moreover, in vitro studies demonstrated that suppression of autophagy significantly reduced the OGD-induced inflammatory response. In addition, exosome treatment was more effective in suppressing the inflammatory response by reversing OGD-induced and autophagy-mediated microglial polarization to M1. Furthermore, in vivo studies showed that exosomes derived from ADSCs significantly decreased the cerebral injury area of infarction by suppressing autophagy and promoting M2 microglia/macrophage polarization. CONCLUSIONS: Our results suggest that miR-30d-5p-enhanced ADSC-derived exosomes prevent cerebral injury by inhibiting autophagy-mediated microglial polarization to M1.

Downregulation of circ_008018 protects against cerebral ischemia-reperfusion injury by targeting miR-99a.

Circular RNAs (circRNAs) are highly expressed in eukaryotic cells and regulate physiological and pathophysiological processes. However, the role of circRNAs in cerebral ischemia-reperfusion (I/R) injury remains largely unknown. In this study, we found that circ_008018 level was higher in the cortical tissue of mice with middle cerebral artery occlusion as compared to those in the sham group 24 h after reperfusion. Knockdown of circ_008018 attenuated cerebral I/R-induced brain tissue damage and neurological deficits in mice by inducing microRNA miR-99a overexpression. The decreased phosphorylation of Akt and glycogen synthase kinase 3ß caused by I/R was partly reversed by circ_008018 silencing or miR-99a overexpression. Taken together, these results provide new insight into the mechanisms of apoptosis resulting from cerebral I/R injury and suggest that targeted inhibition of circ_008018 can protect against subsequent neurological damage.

Myocardial strain may be useful in differentiating Takotsubo cardiomyopathy from left anterior descending coronary artery ischemia.

BACKGROUND: Stress-induced cardiomyopathy (SCM) is characterized by transient apical wall motion abnormalities of the left ventricle (LV) in the absence of obstructive coronary artery disease. Although the echocardiographic findings of SCM mimic those of left anterior descending coronary artery ischemia or infarction (LAD), the regional LV wall motion pattern and degree of RV involvement may differ. METHODS: We sought to systematically assess regional LV and RV function with myocardial strain imaging to assess if ventricular involvement may differ between SCM and LAD. RESULTS: This was a retrospective cohort study, with 3 groups: patients with SCM (n=55), patients with LAD (n=36), and 37 normal subjects. All the patients had a comprehensive transthoracic echocardiographic examination, including assessment of longitudinal strain (LS). Global LV longitudinal strain was markedly decreased in both the SCM and LAD groups. However, SCM patients differed by more severe involvement the mid-inferolateral, mid-inferior, apical-lateral, and apical-inferior segments. When compared to the LAD patients, SCM patients had significantly more RV involvement both visually and quantitatively (27-42% versus 0-25%). Predictors of SCM included visually reduced RV systolic function, abnormal TAPSE, RVS' and RV LS in the apical segment. Of the LV variables, regional LS in the mid-inferior and apical-inferior segments could differentiate the groups. CONCLUSIONS: Our results suggest that RV involvement and the pattern of LV regional LS abnormalities may help differentiate SCM from LAD disease during echocardiographic imaging.

[Research on engine remaining useful life prediction based on oil spectrum analysis and particle filtering].

The spectrometric oil analysis(SOA) is an important technique for machine state monitoring, fault diagnosis and prognosis, and SOA based remaining useful life(RUL) prediction has an advantage of finding out the optimal maintenance strategy for machine system. Because the complexity of machine system, its health state degradation process can't be simply characterized by linear model, while particle filtering(PF) possesses obvious advantages over traditional Kalman filtering for dealing nonlinear and non-Gaussian system, the PF approach was applied to state forecasting by SOA, and the RUL prediction technique based on SOA and PF algorithm is proposed. In the prediction model, according to the estimating result of system's posterior probability, its prior probability distribution is realized, and the multi-step ahead prediction model based on PF algorithm is established. Finally, the practical SOA data of some engine was analyzed and forecasted by the above method, and the forecasting result was compared with that of traditional Kalman filtering method. The result fully shows the superiority and effectivity of the

Luteinizing-hormone-releasing-hormone-containing biodegradable polymer micelles for enhanced intracellular drug delivery.

A biodegradable triblock copolymer, poly(ethylene oxide)-block-poly(allyl glycidyl ether)-block-poly(dl-lactide) (mPEG-b-PAGE-b-PLA), with allyl groups on its middle block was designed and synthesized through anionic polymerization of allyl glycidyl ether (AGE) with PEG monomethyl ether sodium salt as the macroinitiator and subsequent ring-opening polymerization of dl-lactide. Luteinizing hormone-releasing hormone (LHRH) was conjugated to the PAGE block through a linkage of -SCH2CH2C([double bond, length as m-dash]O)NH- between the allyl and LHRH residues. The LHRH content in the conjugate was ca. 25 wt%. Owing to the amphiphilic nature of the conjugate, it was self-assembled into micelles of 15-40 nm in diameter and with the LHRH moieties in the hydrophilic corona of the micelles. Cellular uptake experiments were carried out using flow cytometry and confocal laser scanning microscopy (CLSM) with HeLa cells as LHRH-receptor overexpressing cells and HepG-2 cells as normal cells. HeLa cells displayed more cellular uptake of the LHRH-micelles than the normal cells. In vivo biodistribution of the LHRH-containing micelles and LHRH-free micelles was studied using a CRI Maestro™ imaging system. Preferred accumulation in tumor sites of LHRH-containing micelles was observed at 24 hours post injection. Therefore, LHRH-conjugated amphiphilic copolymers might be used as a potential drug delivery system for the treatment of LHRH receptor overexpressing carcinoma.

Meta-analysis on association between the ATP-binding cassette transporter A1 gene (ABCA1) and Alzheimer's disease.

PURPOSE: In the past decade, a number of case-control studies have been carried out to investigate the relationship between ABCA1 polymorphisms and Alzheimer's disease (AD). However, these studies have yielded contradictory results. To investigate this inconsistency, a meta-analysis was performed. METHODS: Databases including PubMed, Web of Science, EMBASE and CNKI were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. RESULTS: A total of 13 case-control studies, involving 6214 patients and 6034 controls for ABCA1 polymorphisms were included. In a combined analysis, the summary per-allele odds ratio for AD of the 219K was 1.03 (95% CI: 0.93-1.14, p=0.56). A meta-analysis of studies on the 883M and 1587K variant showed no significant overall association with AD, yielding a per-allele odds ratio of 1.10 (95% CI: 0.96-1.26, p=0.16), and 1.09 (95% CI: 0.97-1.24, p=0.16) respectively. Similar results were also found for heterozygous and homozygous. In the subgroup analysis by ethnicity, sample size, APOE status and onset type, no significant associations were found in almost all genetic models. CONCLUSIONS: In summary, there was no significant association detected between ABCA1 R219K, I883M and R1587K polymorphisms and risk for AD.

Preeclampsia activates 15-lipoxygenase and its metabolite 15-hydroxyeicosatetraenoic acid enhances constriction in umbilical arteries.

OBJECTIVE: To compare the differential expression of 15-lipoxygenase (15-LO) isoenzymes, 15-LO-1 and 15-LO-2 in preeclampsia (PE), and normal pregnancy and its metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) on the vasoconstriction of human umbilical artery (HUA) rings. STUDY DESIGN: We performed western blotting and isometric tension studies and t-test analysis on data from 6 women with normal pregnancy and 8 women with PE. RESULTS: Expressions of 15-LO-1 and 15-LO-2 in placentas and HUA rings in PE increased more than that in normal groups (P<0.01). 15-HETE increased HUA rings tension in a dose-dependence manner, which were significantly greater in PE than in normal pregnant controls (P<0.01). However, the constriction of HUA rings was completely eliminated by 2-aminoethoxydiphenyl borate (2-APB) in both normal pregnancy and PE (P<0.01) and attenuated partly by nifedipine in dose-dependence in normal pregnancy (10(-8)mol/L P>0.05; 10(-7), 10(-6)mol/L P<0.05) and in PE (P<0.01). CONCLUSION: PE upregulates 15-LO pathway via 15-HETE, which increased intercellular calcium level to cause constriction of HUA rings.

Induction of pluripotent stem cells transplantation therapy for ischemic stroke.

Stroke can cause permanent neurological damage, complications, and even death. However, there is no treatment exists to restore its lost function. Human embryonic stems transplantation therapy was a novel and potential therapeutic approach for stroke. However, as we have seen, the ethical controversy pertains to embryonic stem cell research. Human induced pluripotent stem cells (iPSCs) are the latest generation of stem cells that may be a solution to the controversy of using embryonic cells. In our study, we generated iPSCs from adult human fibroblasts by introduction of four defined transcription factors (Oct4, Sox2, Nanog, and Lin-28). And then, we investigated the efficacy of iPSCs transplantation therapy for stroke on the animal models of middle cerebral artery occlusion. Surprisingly, we found that transplanted iPSCs migrated to injured brain areas, and differentiated into neuron-like cells successfully. After 4-16 days iPSCs grafting, sensorimotor function of rats has been improved significantly. In one word, we may prove that iPSCs therapy in stroke to be an effective form of treatment.

Inhibitory effect of small interfering RNA targeting insulin-like growth factor-I receptor in ovarian cancer OVCAR3 cells.

AIM: Insulin-like growth factor-I receptor (IGF-IR) is widely overexpressed in a variety of human cancers including ovarian cancer. It plays an important role in cancer cell proliferation and tumor growth. In this study, small interfering RNA (siRNA) was used to silence IGF-IR gene expression in the human ovarian cancer cell line OVCAR3 and then its effects on proliferation, apoptosis, angiogenesis, and the growth of tumor cells in vitro and in nude mice were evaluated. METHODS: Three siRNA sequences for the IGF-IR gene were cloned into expression plasmids and transfected into OVCAR3 cells. The downregulation of IGF-IR expression at both mRNA and protein levels were detected by real-time polymerase chain reaction and western blot analysis. Cell proliferation inhibition rates were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Nude mice (n = 6 per group) were subcutaneously xenografted with 2 × 10(6) OVCAR3 cancer cells. Tumor growth, cellular proliferation (Ki-67 immunohistochemistry), apoptosis, and angiogenesis (CD31 immunohistochemistry) were compared for mice administered either IGF-IR-specific or negative control siRNA over 5 weeks. RESULTS: The mRNA and protein expression of IGF-IR was significantly decreased at 48 hours after transfection, leading to a potent suppression of tumor cell proliferation in vitro. The IGF-IR-specific siRNA dramatically suppressed tumor growth and cellular proliferation, as well as promoted tumor cellular apoptosis and inhibited angiogenesis in an OVCAR3 s.c. xenograft model. CONCLUSIONS: The siRNA targeting of IGF-IR can effectively inhibit the growth of ovarian cancer cells and may be used as a potent therapy.