Prenatal prednisone exposure impacts liver development and function in fetal mice and its characteristics.

Prednisone, a widely used glucocorticoid drug in human and veterinary medicine, has been reported to cause developmental toxicity. However, systematic studies about the effect of prednisone on fetal liver development are still unclear. We investigated the potential effects of maternal exposure to clinically equivalent doses of prednisone during different gestational stages on cell proliferation and apoptosis, cell differentiation, glucose and lipid metabolism, and hematopoiesis in the liver of fetal mice, and explored the potential mechanisms. Results showed that prenatal prednisone exposure (PPE) could suppress cell proliferation, inhibit hepatocyte differentiation, and promote cholangiocyte differentiation in the fetal liver. Meanwhile, PPE could result in the enhancement of glyconeogenesis and bile acid synthesis and the inhibition of fatty acid ß-oxidation and hematopoiesis in the fetal liver. Further analysis found that PPE-induced alterations in liver development had obvious stage and sex differences. Overall, the alteration in fetal liver development and function induced by PPE was most pronounced during the whole pregnancy (GD0-18), and the males were relatively more affected than the females. Additionally, fetal hepatic insulin-like growth factor 1 (IGF1) signaling pathway was inhibited by PPE. In conclusion, PPE could impact fetal liver development and multiple functions, and these alterations might be partially related to the inhibition of IGF1 signaling pathway.

Overcoming barriers for left atrial appendage thrombus: a systematic review of left atrial appendage closure.

BACKGROUND: Approximately 90% of intracardial thrombi originate from the left atrial appendage in non-valvular atrial fibrillation patients. Even with anticoagulant therapy, left atrial appendage thrombus (LAAT) still occurs in 8% of patients. While left atrial appendage closure (LAAC) could be a promising alternative, the current consensus considers LAAT a contraindication to LAAC. However, the feasibility and safety of LAAC in patients with LAAT have yet to be determined. METHODS: This systematic review synthesizes published data to explore the feasibility and safety of LAAC for patients with LAAT. RESULTS: This study included a total of 136 patients with LAATs who underwent successful LAAC. The Amulet Amplatzer device was the most frequently utilized device (48.5%). Among these patients, 77 (56.6%) had absolute contraindications to anticoagulation therapy. Cerebral protection devices were utilized by 47 patients (34.6%). Transesophageal echocardiography (TEE) is the primary imaging technique used during the procedure. Warfarin and novel oral anticoagulants were the main anticoagulant medications used prior to the procedure, while dual antiplatelet therapy was primarily used post-procedure. During a mean follow-up period of 13.2 ± 11.5 months, there was 1 case of fatality, 1 case of stroke, 3 major bleeding events, 3 instances of device-related thrombus, and 8 cases of peri-device leakage. CONCLUSIONS: This review highlights the preliminary effectiveness and safety of the LAAC procedure in patients with persistent LAAT. Future large-scale RCTs with varied LAAT characteristics and LAAC device types are essential for evidence-based decision-making in clinical practice.

Epigenetic programming mediates abnormal gut microbiota and disease susceptibility in offspring with prenatal dexamethasone exposure.

Prenatal dexamethasone exposure (PDE) can lead to increased susceptibility to various diseases in adult offspring, but its effect on gut microbiota composition and the relationship with disease susceptibility remains unclear. In this study, we find sex-differential changes in the gut microbiota of 6-month-old infants with prenatal dexamethasone therapy (PDT) that persisted in female infants up to 2.5 years of age with altered bile acid metabolism. PDE female offspring rats show abnormal colonization and composition of gut microbiota and increased susceptibility to cholestatic liver injury. The aberrant gut microbiota colonization in the PDE offspring can be attributed to the inhibited Muc2 expression caused by decreased CDX2 expression before and after birth. Integrating animal and cell experiments, we further confirm that dexamethasone could inhibit Muc2 expression by activating GR/HDAC11 signaling and regulating CDX2 epigenetic modification. This study interprets abnormal gut microbiota and disease susceptibility in PDT offspring from intrauterine intestinal dysplasia.

Device therapy for patients with atrial fibrillation and heart failure with preserved ejection fraction.

Device therapy is a nonpharmacological approach that presents a crucial advancement for managing patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). This review investigated the impact of device-based interventions and emphasized their potential for optimizing treatment for this complex patient demographic. Cardiac resynchronization therapy, augmented by atrioventricular node ablation with His-bundle pacing or left bundle-branch pacing, is effective for enhancing cardiac function and establishing atrioventricular synchrony. Cardiac contractility modulation and vagus nerve stimulation represent novel strategies for increasing myocardial contractility and adjusting the autonomic balance. Left ventricular expanders have demonstrated short-term benefits in HFpEF patients but require more investigation for long-term effectiveness and safety, especially in patients with AF. Research gaps regarding complications arising from left ventricular expander implantation need to be addressed. Device-based therapies for heart valve diseases, such as transcatheter aortic valve replacement and transcatheter edge-to-edge repair, show promise for patients with AF and HFpEF, particularly those with mitral or tricuspid regurgitation. Clinical evaluations show that these device therapies lessen AF occurrence, improve exercise tolerance, and boost left ventricular diastolic function. However, additional studies are required to perfect patient selection criteria and ascertain the long-term effectiveness and safety of these interventions. Our review underscores the significant potential of device therapy for improving the outcomes and quality of life for patients with AF and HFpEF.

Protective effects of catalpol on cardio-cerebrovascular diseases: A comprehensive review.

Catalpol, an iridoid glucoside isolated from Rehmannia glutinosa, has gained attention due to its potential use in treating cardio-cerebrovascular diseases (CVDs). This extensive review delves into recent studies on catalpol's protective properties in relation to various CVDs, such as atherosclerosis, myocardial ischemia, infarction, cardiac hypertrophy, and heart failure. The review also explores the compound's anti-oxidant, anti-inflammatory, and anti-apoptotic characteristics, emphasizing the role of vital signaling pathways, including PGC-1α/TERT, PI3K/Akt, AMPK, Nrf2/HO-1, estrogen receptor (ER), Nox4/NF-κB, and GRP78/PERK. The article discusses emerging findings on catalpol's ability to alleviate diabetic cardiovascular complications, thrombosis, and other cardiovascular-related conditions. Although clinical studies specifically addressing catalpol's impact on CVDs are scarce, the compound's established safety and well-tolerated nature suggest that it could be a valuable treatment alternative for CVD patients. Further investigation into catalpol and related iridoid derivatives may unveil new opportunities for devising natural and efficacious CVD therapies.

Azithromycin exposure during pregnancy disturbs the fetal development and its characteristic of multi-organ toxicity.

AIMS: Azithromycin is widely used in clinical practice for treating maternal infections during pregnancy. Meanwhile, azithromycin, as an "emerging pollutant", is increasingly polluting the environment due to the rapidly increasing usage (especially after the COVID-19). Previous studies have suggested a possible teratogenic risk of prenatal azithromycin exposure (PAzE), but its effects on fetal multi-organ development are still unclear. This study aimed to explore the potential impacts of PAzE. MATERIALS AND METHODS: We focused on pregnancy outcomes, maternal/fetal serum phenotypes, and fetal multiple organ development in mice at different doses (50/200 mg/kg·d) during late pregnancy or at 200 mg/kg·d during different stages (mid-/late-pregnancy) and courses (single-/multi-course). KEY FINDINGS: The results showed PAzE increased the rate of the absorbed fetus during mid-pregnancy and increased the intrauterine growth retardation rate (IUGR) during late pregnancy. PAzE caused multiple blood phenotypic changes in maternal and fetal mice, among which the number and degree of changes in fetal blood indicators were more significant. Moreover, PAzE inhibited long bone/cartilage development and adrenal steroid synthesis, promoting hepatic lipid production and ovarian steroid synthesis in varying degrees. The order of severity might be bone/cartilage > liver > gonads > other organs. PAzE-induced multi-organ alterations differed in stages, courses doses and fetal sex. The most apparent changes might be in high-dose, mid-pregnancy, multi-course, and female, while there was no typical rule for a dose-response relationship. SIGNIFICANCE: This study confirmed PAzE could cause fetal developmental abnormalities and multi-organ functional alterations, which deepens the comprehensive understanding of azithromycin's fetal developmental toxicity.

Lactational retrorsine exposure changes maternal milk components and disturbs metabolism homeostasis of offspring rats.

Pyrrolizidine alkaloids (PAs) are a type of plant-derived environmental toxins, which pose a health hazard to human and livestock via contaminating soil, water, plants and food. In this study, we aimed to investigate the effect of lactational retrorsine (RTS, a typical toxic PA) exposure on breastmilk components and glucose-lipid metabolism of offspring rats. Dams were intragastrically administered with 5 mg/(kg·d) RTS during lactation. After metabolomic analyses, 114 differential constituents were identified in breastmilk between control and RTS groups, featured by reduction of lipids and lipid-like molecules, while presence of abundant RTS and its derivative in RTS-exposed milk. RTS exposure induced liver injury in pups, but the leakage of transaminases in serum recovered in their adulthood. Serum glucose levels were lower in pups but higher in male adult offspring from RTS group. RTS exposure also induced hypertriglyceridemia, hepatic steatosis and decreased glycogen content in both pups and adult offspring. Additionally, suppression of PPARα-FGF21 axis persisted in offspring liver after RTS exposure. These data indicated that inhibition of PPARα-FGF21 axis induced by milk deficient in lipid contents, together with hepatotoxic injury caused by RTS in breastmilk, may disrupt glucose and lipid metabolism of pups, and the persistent suppression of PPARα-FGF21 axis may program metabolic disorder of glucose and lipid in adult offspring.

Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy.

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

Ginsenoside Rc: A potential intervention agent for metabolic syndrome.

Ginsenoside Rc, a dammarane-type tetracyclic triterpenoid saponin primarily derived from Panax ginseng, has garnered significant attention due to its diverse pharmacological properties. This review outlined the sources, putative biosynthetic pathways, extraction, and quantification techniques, as well as the pharmacokinetic properties of ginsenoside Rc. Furthermore, this study explored the pharmacological effects of ginsenoside Rc against metabolic syndrome (MetS) across various phenotypes including obesity, diabetes, atherosclerosis, non-alcoholic fatty liver disease, and osteoarthritis. It also highlighted the impact of ginsenoside Rc on multiple associated signaling molecules. In conclusion, the anti-MetS effect of ginsenoside Rc is characterized by its influence on multiple organs, multiple targets, and multiple ways. Although clinical investigations regarding the effects of ginsenoside Rc on MetS are limited, its proven safety and tolerability suggest its potential as an effective treatment option.

Prenatal dexamethasone exposure induced pancreatic ß-cell dysfunction and glucose intolerance of male offspring rats: Role of the epigenetic repression of ACE2.

The prevalence of diabetes in children and adolescents has been rising gradually, which is relevant to adverse environment during development, especially prepartum. We aimed to explore the effects of prenatal dexamethasone exposure (PDE) on ß-cell function and glucose homeostasis in juvenile offspring rats. Pregnant Wistar rats were subcutaneously administered with dexamethasone [0.1, 0.2, 0.4mg/(kg.d)] from gestational day 9 to 20. PDE impaired glucose tolerance in the male offspring rather than the females. In male offspring, PDE impaired the development and function of ß-cells, accompanied with lower H3K9ac, H3K14ac and H3K27ac levels in the promoter region of angiotensin-converting enzyme 2 (ACE2) as well as suppressed ACE2 expression. Meanwhile, PDE increased expression of glucocorticoid receptor (GR) and histone deacetylase 3 (HDAC3) in fetal pancreas. Dexamethasone also inhibited ACE2 expression and insulin production in vitro. Recombinant expression of ACE2 restored insulin production inhibited by dexamethasone. In addition, dexamethasone activated GR and HDAC3, increased protein interaction of GR with HDAC3, and promoted the binding of GR-HDAC3 complex to ACE2 promoter region. Both RU486 and TSA abolished dexamethasone-induced decline of histone acetylation and ACE2 expression. In summary, suppression of ACE2 is involved in PDE induced ß-cell dysfunction and glucose intolerance in juvenile male offspring rats.

Identification and validation of reference genes for RT-qPCR analysis in fetal rat pancreas.

The choice of reference gene is crucial for quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) assay. To screen and determine the suitable reference genes in fetal rat pancreas, we selected eight candidate reference genes (Gapdh, Actb, Rn18 s, B2m, Rpl13a, Tbp, Ywhaz and Ubc), and evaluated the constancy of gene expression from fetal rat pancreases in non-pathological situation and prenatal dexamethasone exposure (PDE) model, using four algorithms: GeNorm, NormFinder, Bestkeeper and Comparative ΔCt method. In addition, the alteration of mRNA levels of pancreatic insulin was compared between control and PDE groups to validate the reliability of selected reference genes for data normalization of RT-qPCR. The comprehensive ranking of reference genes under physiological condition was as follow: Gapdh > Actb > Ywhaz > Ubc > Rn18s > Rpl13a > B2m > Tbp (female); Actb > Ywhaz > Gapdh > Ubc > B2m > Rpl13a > Rn18 s | Tbp (male). The top ranking reference genes were also stably expressed in PDE fetal pancreas. The best reference gene combinations are: Ywhaz+Actb for female and Ywhaz+Gapdh for male fetal rat pancreas, respectively. Compared with low ranking or single reference gene, the change trend of insulin mRNA normalized by the best reference gene combination between control and PDE groups was more significant and consistent with that of serum insulin level. In conclusion, our results provided the optimal combination of stable reference genes for RT-qPCR assay in pancreatic developmental toxicity study.

Prenatal Exposure to Retrorsine Induces Developmental Toxicity and Hepatotoxicity of Fetal Rats in a Sex-Dependent Manner: The Role of Pregnane X Receptor Activation.

Pyrrolizidine alkaloids (PAs) are a type of natural phytotoxin that contaminate food and feed and become an environmental health risk to humans and livestock. PAs exert toxicity that requires metabolic activation by cytochrome P450 (CYP) 3A, and case reports showed that fetuses are quite susceptible to PAs toxicity. The aim of this study was to explore the characteristics of developmental toxicity and fetal hepatotoxicity induced by retrorsine (RTS, a typcial toxic PA) and the underlying mechanism. Pregnant Wistar rats were intragastrically administered with 20 mg/(kg·day) RTS from gestation day (GD) 9 to 20. Results showed that prenatal RTS exposure lowered fetal bodyweights, reduced hepatocyte numbers, and potentiated hepatic apoptosis in fetuses, particularly females. Simutaneously, RTS increased CYP3A expression and pregnane X receptor (PXR) activation in female fetal liver. We further confirmed that RTS was a PXR agonist in LO2 and HepG2 cell lines. Furthermore, agonism or antagonism of androgen receptor (AR) either induced or blocked RTS-mediated PXR activation, respectively. As a PXR agonist, RTS toxicity was exacerbated in female fetus due to the increased CYP3A induction and self-metabolism, while the inhibitory effect of AR on PXR activation reduced the susceptibility of male fetus to RTS. Our findings indicated that PXR may be a potential therapeutic target for PA toxicity.

Prenatal dexamethasone exposure induces nonalcoholic fatty liver disease in male rat offspring via the miR-122/YY1/ACE2-MAS1 pathway.

Epidemiological studies have shown that nonalcoholic fatty liver disease (NAFLD) has an intrauterine developmental origin. We aimed to demonstrate that NAFLD is caused by prenatal dexamethasone exposure (PDE) in adult male rat offspring and to investigate the intrauterine programming mechanism. Liver samples were obtained on gestational day (GD) 21 and postnatal week (PW) 28. The effects and epigenetic mechanism of dexamethasone were studied with bone marrow mesenchymal stem cells (BMSCs) hepatoid differentiated cells and other cell models. In the PDE group, lipid accumulation increased, triglyceride synthesis-related gene expression increased, and oxidation-related gene expression decreased in livers of adult male rat offspring. In utero, hepatic triglyceride synthesis increased and oxidative function decreased in PDE fetal male rats. Moreover, low hepatic miR-122 expression, high Yin Yang-1 (YY1) expression and angiotensin-converting enzyme 2 (ACE2)-Mas receptor (MAS1) signaling pathway inhibition were observed before and after birth. At the cellular level, dexamethasone (100-2500 nM) elevated the intracellular triglyceride content, increased triglyceride synthesis-related gene expression and decreased oxidation-related gene expression. Dexamethasone treatment also decreased miR-122 expression, increased YY1 expression and inhibited the ACE2-MAS1 signaling pathway. Interference or overexpression of glucocorticoid receptor (GR), miR-122, YY1 and ACE2 could reverse the changes in downstream gene expression. In summary, PDE could induce NAFLD in adult male rat offspring. The programming mechanism included inhibition of miR-122 expression after GR activation, and dexamethasone increased hepatocyte YY1 expression; these effects resulted in ACE2-MAS1 signaling pathway inhibition, which led to increased hepatic triglyceride synthesis and decreased oxidative function. The increased triglyceride synthesis and decreased oxidative function of hepatocytes caused by low miR-122 expression due to dexamethasone could continue postnatally, eventually leading to NAFLD in adult rat offspring.

Epigenetic repression of AT2 receptor is involved in ß cell dysfunction and glucose intolerance of adult female offspring rats exposed to dexamethasone prenatally.

Prenatal exposure to dexamethasone (PDE) impairs pancreatic ß cell development and glucose homeostasis in offspring especially females. To explore the underlying intrauterine programming mechanism, pregnant Wistar rats were subcutaneously administered with dexamethasone (0, 0.2 and 0.8 mg/kg·d) from gestational days (GD) 9 to 20. Female offspring were collected on GD20 (fetus) and in postnatal week 28 (adult), respectively. PDE reduced the serum insulin levels, ß cell mass, and pancreatic insulin expressions in fetuses and adults, causing glucose intolerance after maturity. The persistent suppression of pancreatic angiotensin II receptor type 2 (AT2R) expression before and after birth could be observed in the PDE females, which is accompanied with decreased histone 3 lysine 14 acetylation (H3K14ac) and H3K27ac levels in AT2R promoter. PDE increased the gene expressions of glucocorticoid receptor (GR) and histone deacetylase 2 (HDAC2) in fetal pancreas. Furthermore, dexamethasone inhibited insulin biosynthesis while activated GR and HDAC2 expression in the rat INS-1 cells. The AT2R expression was repressed by dexamethasone in vitro but only H3K27ac levels in AT2R promoter were lowered. Dexamethasone enhanced the interaction between GR and HDAC2 proteins as well as the binding of GR/HDAC2 complex to AT2R promoter. Moreover, overexpression of AT2R could restore the suppressed insulin biosynthesis induced by dexamethasone in vitro, and both GR antagonist and histone deacetylase abolished the decreased H3K27ac level and gene expression of AT2R. In conclusion, continuous epigenetic repression of AT2R before and after birth may be involved in ß cell dysfunction and glucose intolerance of the PDE adult female offspring.

Female-specific activation of pregnane X receptor mediates sex difference in fetal hepatotoxicity by prenatal monocrotaline exposure.

Pyrrolizidine alkaloids (PAs) are a group of hepatic toxicant widely present in plants. Cytochrome P450 (CYP) 3A plays a key role in metabolic activation of PAs to generate electrophilic metabolites, which is the main cause of hepatotoxicity. We have previously demonstrated the sex difference in developmental toxicity and hepatotoxicity in fetal rats exposed to monocrotaline (MCT), a representative toxic PA. The aim of this study was to explore the underlying mechanism. 20 mg·kg-1·d-1 MCT was intragastrically given to pregnant Wistar rats from gestation day 9 to 20. CYP3As expression and pregnane X receptor (PXR) activation were specifically enhanced in female fetal liver. After MCT treatment, we also observed a significant increase of CYP3As expression in LO2 cells (high PXR level) or hPXR-transfected HepG2 cells (low PXR level). Employing hPXR and CYP3A4 dual-luciferase reporter gene assay, we confirmed the agonism effect of MCT on PXR-dependent transcriptional activity of CYP3A4. Agonism and antagonism of the androgen receptor (AR) either induced or blocked MCT-induced PXR activation, respectively. This study was the first report identifying that MCT served as PXR agonist to induce CYP3A expression. CYP3A induction may increase self-metabolic activation of MCT and subsequently lead to more severe hepatotoxicity in female fetus. While in male, during the intrauterine period, activated AR by testosterone secretion from developing testes represses MCT-induced PXR activation and CYP3A induction, which may partially protect male fetus from MCT-induced hepatotoxicity.

Involvement of organic cation transporter 2 in the metformin-associated increased lactate levels caused by contrast-induced nephropathy.

The application of iodinated contrast medium has become a risk factor for metformin-associated lactic acidosis (MALA), which leads to the accumulation of metformin in vivo is one of the principal reasons for MALA. However, the molecular mechanism of the adverse event is not yet clear. In this study, iohexol injection was used as a model drug. The contrast agent acute kidney injury rat model, in vivo rat pharmacokinetic study, kidney slices and HK-2 cells were performed to elucidate the pharmacokinetic molecular mechanism of accumulation of metformin caused by contrast-induced nephropathy (CIN). Plasma exposure of metformin was increased significantly in the CIN group compared with that in the normal and control groups. The AUC of metformin was from 2791 ±â€¯382 µg min mL-1 to 4784 ±â€¯767 µg min mL-1. The cumulative urinary excretion of metformin was also reduced in the CIN group. The uptake of metformin decreased in kidney slices in the CIN group. Compared with the normal and control groups, the blood lactate concentration was increased after intravenous administration of metformin in the CIN group followed a similar trend to the plasma concentrations of metformin. After treatment with contrast medium, the expression of OCT2 was reduced in rat kidney and HK-2 cells. These findings highlight that OCT2 deficiency was associated with increased lactate levels during metformin treatment caused by CIN.

Activating the PGC-1α/TERT Pathway by Catalpol Ameliorates Atherosclerosis via Modulating ROS Production, DNA Damage, and Telomere Function: Implications on Mitochondria and Telomere Link.

Catalpol, an iridoid glucoside, has been found present in large quantities in the root of Rehmannia glutinosa L. and showed a strong antioxidant capacity in the previous study. In the present work, the protective effect of catalpol against AS via inhibiting oxidative stress, DNA damage, and telomere shortening was found in LDLr-/- mice. This study also shows that activation of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)/telomerase reverse transcriptase (TERT) pathway, which is the new link between mitochondria and telomere, was involved in the protective effects of catalpol. Further, by using PGC-1α or TERT siRNA in oxLDL-treated macrophages, it is proved that catalpol reduced oxidative stress, telomere function, and related DNA damage at least partly through activating the PGC-1α/TERT pathway. Moreover, dual luciferase activity assay-validated catalpol directly enhanced PGC-1α promoter activity. In conclusion, our study revealed that the PGC-1α/TERT pathway might be a possible therapeutic target in AS and catalpol has highly favorable characteristics for the treatment of AS via modulating this pathway.

The anti-tumor effects of the recombinant toxin protein rLj-RGD3 from Lampetra japonica on pancreatic carcinoma Panc-1 cells in nude mice.

Recombinant Lampetra japonica RGD peptide (rLj-RGD3) is a soluble toxin protein with three RGD (Arg-Gly-Asp) motifs and a molecular weight of 13.5kDa. The aim of this study was to investigate the effects and mechanisms of rLj-RGD3 on tumor growth and survival in pancreatic carcinoma Panc-1 cell-bearing mice. A Panc-1 human pancreatic carcinoma-bearing nude mouse model was successfully generated, and the animals were treated with different doses of rLj-RGD3 for 3 weeks. The volume and weight of the subcutaneous tumors, the survival of the nude mice, histopathological changes, the intratumoral MVD, the number of apoptotic Panc-1 cells, and apoptosis-related proteins and gene expressions were determined. rLj-RGD3 significantly decreased the tumor volumes and weights, and the maximum tumor volume and weight IR values were 53.2% (p<0.001) and 55.9% (p<0.001), respectively. The life expectancy of Panc-1-bearing nude mice treated with rLj-RGD3 was increased by 56.3% (p<0.001). Meanwhile, rLj-RGD3 promoted the expression of Bax, caspase-3, and caspase-9 and inhibited Bcl-2 and VEGF expression. In addition, rLj-RGD3 did not change FAK, PI3K and Akt expression, but p-FAK, p-PI3K and p-Akt, levels were down-regulated. These results show that rLj-RGD3 induced potent anti-tumor activity in vivo and suppressed the growth of transplanted Panc-1 cells in a nude mouse model, implying that rLj-RGD3 may serve as a potent clinical therapeutic agent for human pancreatic carcinoma.