Effects of miR-490-5p targeting CDK1 on proliferation and apoptosis of colon cancer cells via ERK signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effects of micro ribonucleic acid (miR)-490-5p on the proliferation and apoptosis of colon cancer cells, and to explore its potential mechanism. PATIENTS AND METHODS: The mRNA expression of miR-490-5p in 30 pairs of colon cancer tissues and adjacent normal tissues was detected via reverse transcription-polymerase chain reaction (RT-PCR). Human colon cancer SW480 cell lines were cultured in vitro and divided into Control group and miR-490-5p overexpression group (miR-490-5p mimic group). The nonsense sequence and miR-490-5p mimic were transfected using liposome transfection technique into colon cancer cells in control group and miR-490-5p mimic group, respectively. Cell proliferation and apoptosis in each group were then observed. At the same time, the effect of miR-490-5p on the growth of colon cancer in vivo was explored using subcutaneous tumorigenesis assay. The protein expressions of extracellular signal-regulated kinase (ERK)1/2 signaling pathway and cyclin-dependent kinase 1 (CDK1) were determined via Western blotting. Furthermore, immunohistochemical staining was performed to verify the protein expression of CDK1 in vivo. RESULTS: The expression of miR-490-5p in colon cancer tissues was significantly lower than that in adjacent normal tissues (p<0.05). After transfection with miR-490-5p mimic in vitro, EdU staining and colony formation assay showed that the proliferation ability of SW480 cells was significantly weakened (p<0.05). Meanwhile, the number of colonies in miR-490-5p mimic group was markedly less than that in Control group (p<0.05). The results of Western blotting revealed that overexpression of miR-490-5p remarkably up-regulated the Bax/Bcl-2 and C-Caspase3/T-Caspase3 ratios in cancer cells (p<0.05). Subsequent results indicated that the subcutaneous tumorigenesis of colon cancer cells was markedly inhibited by overexpression of miR-490-5p (p<0.05). According to the results of Western blotting, the activation of ERK signaling pathway and the protein expression of CDK1 were significantly suppressed by overexpression of miR-490-5p (p<0.05). In vivo experiments further revealed that the protein expression of CDK1 in colon cancer tissues increased significantly (p<0.05). CONCLUSIONS: MiR-490-5p was found lowly expressed in colon cancer patients. In addition, overexpression of miR-490-5p inhibited the proliferation and promoted the apoptosis of colon cancer cells via down-regulating CDK1 both in vitro and in vivo.

Perinatal exposure to di-(2-ethylhexyl) phthalate induces hepatic lipid accumulation mediated by diacylglycerol acyltransferase 1.

INTRODUCTION: Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer in consumer products and medical devices. It is also suspected to exacerbate the development of fatty liver. However, the mechanisms underlying excessive lipid synthesis and its deposition in the liver are yet to be identified. This study was aimed to evaluate the molecular mechanisms of hepatic lipid accumulation in adult male offspring after perinatal exposure to DEHP. METHOD: Corn oil and DEHP (0.75 mg/kg/day) were administered once per day to dam from gestation day 6 to postnatal day (PND) 21 by oral gavage. After the weaning period, DEHP treated male pups were categorized into early life stage- and lifelong period group. Male rats both control and early life stage group administered corn oil, and lifelong period group administered DEHP from PND 22 to 70. Histological examination and triglyceride (TG) levels in the liver were analyzed. Expressions of transcription factors associated with lipid accumulation in the liver were analyzed. RESULTS: Both early life stage- and lifelong period group, hepatic TG levels, and mRNA and protein expression of diacylglycerol acyltransferase 1 (DGAT1) were significantly higher than control (TG: all p < 0.05, mRNA & protein: p < 0.05 and p < 0.001, respectively). The average body weight from PND 35 to 63, and mRNA and protein expression of sterol regulatory element binding protein 1c in lifelong period group were significantly lower than control (all p < 0.05); however, alanine transaminase were significantly higher than control (p < 0.01). CONCLUSION: Perinatal exposure to DEHP may induce the hepatic lipid accumulation through up-regulation of DGAT1 expression.

Effects of lncRNA-HEIH on proliferation, apoptosis and invasion of gastric cancer cells.

OBJECTIVE: The aim of this study was to explore the expression of long non-coding ribonucleic acid HEIH (lncRNA-HEIH) in gastric cancer (GC) tissues, and to investigate its effects on the proliferation, apoptosis and invasion of HGC-27 cells. PATIENTS AND METHODS: A total of 80 tissue samples were collected from patients diagnosed with GC in Shenzhen People's Hospital. Meanwhile, para-carcinoma tissues were enrolled as normal controls (Control group). Total RNA was extracted from tissues, and the expression of lncRNA-HEIH was detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). HGC-27 cells were cultured and transfected with small-interfering RNA-HEIH (si-HEIH group). At 48 h after transfection, cell proliferation, apoptosis and invasion were detected via methyl thiazolyl tetrazolium (MTT) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and transwell assay, respectively. RESULTS: (1) Compared with Control group, the expression of lncRNA-HEIH rose significantly in GC tissues (p<0.01). (2) The expression of lncRNA-HEIH in HGC-27 cells was significantly down-regulated in si-HEIH group compared with si-NC group (p<0.01). (3) Compared with those in si-NC group, the proliferation of HGC-27 cells was suppressed (p<0.05), while the apoptosis of HGC-27 cells was promoted (p<0.01) in si-HEIH group. (4) The invasion of HGC-27 cells was remarkably inhibited in Si-HEIH group than si-NC group (p<0.05). CONCLUSIONS: LncRNA-HEIH is highly expressed in GC patients, which affects the proliferation, apoptosis and invasion of GC HGC-27 cells.

Effects of microRNA-378 on epithelial-mesenchymal transition, migration, invasion and prognosis in gastric carcinoma by targeting BMP2.

OBJECTIVE: Gastric cancer (GC) is a common malignancy. Recent studies have suggested that microRNAs are crucial factors in tumorigenesis. Thus, we investigated the effect of miR-378 on GC metastasis and further explored the underlying mechanism. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was carried out to measure the miR-378 expressions in GC and adjacent normal tissue samples. MiR-378 expressions in human GC cells were determined using qRT-PCR and Western blots. Moreover, transwell assays were conducted to measure the invasion and migration capacities of GC cells. Additionally, the regulating effects on BMP2 by miR-378 were assessed by luciferase reporter assays and western blots. Western blot was also carried out to observe the protein expressions of epithelial-mesenchymal transition (EMT) related genes. RESULTS:  MiR-378 expressions in GC tissues were downregulated. In the meantime, reduced miR-378 expression was associated with poor prognosis and malignant clinicopathologic features of GC patients. MiR-378 overexpression repressed GC cell invasion, migration and EMT. Furthermore, BMP2 was a direct target of miR-378 and implicated in miR-378-mediated suppressive functions in GC invasion, migration and EMT. CONCLUSIONS: We showed that miR-378 served as a tumor suppressor in GC via modulating BMP2, suggesting that miR-378/BMP2 axis might be therapeutic targets and promising biomarkers for GC treatment.

Paeoniflorin attenuates postoperative pain by suppressing Matrix Metalloproteinase-9/2 in mice.

BACKGROUND: Recent studies have implicated that matrix metalloproteinase (MMP)-9 and MMP-2 play key roles in neuropathic pain due to their facilitation of inflammatory cytokine maturation and induction of neuroinflammation. However, the role of MMP-9/2 in postoperative pain is still unclear. We previously suggested that the natural compound paeoniflorin inhibited microglia activation induced by morphine treatment. In the present study, we demonstrated that paeoniflorin could alleviate postoperative pain via specific inhibition of matrix metalloproteinases (MMPs). METHODS: Mice received a plantar incision surgery and their mechanical allodynia was assessed with von Frey filaments. The activity of MMP-9/2 was determined by gelatin zymography. Cell signalling was assayed by western blot and immunohistochemistry. RESULTS: The expression of MMP-9/2 was significantly increased in mice spinal cords with plantar incision surgery. Paeoniflorin remarkably suppressed the activity of MMP-9/2 and relieved plantar incision-induced mechanical allodynia. Interestingly, the administration of paeoniflorin blocked the maturation of interleukin-1ß, which is a critical substrate of MMPs. Thereafter, paeoniflorin markedly suppressed microglia activation, inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and the expression of neuronal c-Fos. CONCLUSION: These results indicated that MMP-9/2 activation in spinal microglia plays a key role in incision-induced mechanical allodynia in mice. Moreover, utilizing paeniflorin blockage of the microglia MMP-9/2 activity might represent a valuable alternative for treating postoperative pain. SIGNIFICANCE: Our results provided direct evidence for the first time that paeoniflorin can inhibit plantar incision-induced microglia TLR4/MMP-9/2/IL-1ß signalling pathway and suppress postoperative pain. Thus, regulation of microglia MMP-9/2 may provide a new strategy for ameliorating postoperative pain.

Prognostic factors for the outcome of extracorporeal shockwave therapy for calcific tendinitis of the shoulder.

AIMS: We conducted a study to identify factors that are prognostic of the outcome of extracorporeal shockwave therapy (ESWT) for calcific tendinitis of the shoulder. PATIENTS AND METHODS: Since 1998, patients with symptomatic calcific tendinitis of the rotator cuff have been treated with ESWT using an electrohydraulic mode shockwave device. One year after ESWT, patients were grouped according to the level of resorption of calcification. RESULTS: Of 241 symptomatic shoulders, complete resorption (CR) of calcification occurred in 134 (CR group). The remaining 107 shoulders had incomplete resorption (ICR) (ICR group). Gartner type I calcification was most common (64.5%) in the ICR group. The mean duration of symptoms before ESWT was significantly longer in the ICR group. Overall, 81% of the CR group and 23.4% of the ICR group were symptom free. There was a strong relationship between subsidence of symptoms and remission of calcification. Poor prognosis was significantly related to Gartner type I calcification, calcification extent > 15 mm and duration of symptoms > 11 months. CONCLUSION: Patients with calcific tendinitis of the shoulder who have the factors identified for a poor outcome after ESWT should undergo a different procedure. Cite this article: Bone Joint J 2017;99-B:1643-50.

Bone marrow cells differentiation into organ cells using stem cell therapy.

Bone marrow cells (BMC) are progenitors of bone, cartilage, skeletal tissue, the hematopoiesis-supporting stroma and adipocyte cells. BMCs have the potential to differentiate into neural cells, cardiac myocytes, liver hepatocytes, chondrocytes, renal, corneal, blood, and myogenic cells. The bone marrow cell cultures from stromal and mesenchymal cells are called multipotent adult progenitor cells (MAPCs). MAPCs can differentiate into mesenchymal cells, visceral mesoderm, neuroectoderm and endoderm in vitro. It has been shown that the stem cells derived from bone marrow cells (BMCs) can regenerate cardiac myocytes after myocardial infarction (MI). Adult bone marrow mesenchymal stem cells have the ability to regenerate neural cells. Neural stem/progenitor cells (NS/PC) are ideal for treating central nervous system (CNS) diseases, such as Alzheimer's, Parkinson's and Huntington disease. However, there are important ethical issues about the therapeutic use of stem cells. Neurons, cardiac myocytes, hepatocytes, renal cells, blood cells, chondrocytes and adipocytes regeneration from BMCs are very important in disease control. It is known that limbal epithelial stem cells in the cornea can repair the eye sight and remove symptoms of blindness. Stem cell therapy (SCT) is progressing well in animal models, but the use of SCT in human remains to be explored further.

Polymer-based disposable microneedle array with insertion assisted by vibrating motion.

This work presents a disposable polymer-based microneedle array that carries out insertions by mimicking the vibrating motion of a mosquito's proboscis. The proposed device, which comprises a 10:1 high-aspect-ratio parylene microneedle array and a chamber structure, was monolithically realized using a novel fabrication process. The vibrating motion of the microneedles was generated using a piezoelectric actuator. This device can be potentially applied to extract and collect blood by puncturing the dermis layer of human skin. The fabricated device is advantageous because of its biocompatibility, simple fabrication process, and low associated costs. Additionally, the graph of the measured extraction flow rate versus the pressure drop that is presented shows an agreement with the results predicted by analytical models. A 40% reduction of insertion force was demonstrated when the microneedle insertion was assisted by actuator-induced vibratory motions. Buckling analyses for estimating the maximum loads that the microneedle can sustain before failure occurs were also evaluated. Finally, the relationship between the insertion force and the vibration frequency was demonstrated in this study.

AIM2 contributes to the maintenance of intestinal integrity via Akt and protects against Salmonella mucosal infection.

The mechanism regulating the gastrointestinal epithelial barrier remains poorly understood. We herein demonstrate that Absent in melanoma-2 (AIM2) contributes to the maintenance of intestinal barrier integrity and defense against bacterial infection. AIM2-deficient mice displayed an increased susceptibility to mucosal but not systemic infection by Salmonella typhimurium, indicating a protective role for AIM2 in the gastrointestinal tract. In a Salmonella colitis model, compared with wild-type mice, AIM2(-/-) mice exhibited more severe body weight loss, intestinal damage, intestinal inflammation, and disruption of basal and activated epithelial cell turnover. In vivo and in vitro data showed that AIM2 restricted the early epithelial paracellular invasion of Salmonella and decreased epithelial permeability. The decreased epithelial barrier in AIM2(-/-) mice might be attributed to the altered expression of tight junction proteins that contribute to epithelial integrity. AIM2 promoted the expression of tight junction proteins through Akt activation. Together, these results suggest that AIM2 is required for maintaining the integrity of the epithelial barrier.

Etiology of renal artery stenosis in 2047 patients: a single-center retrospective analysis during a 15-year period in China.

Systematic investigation with large sample size of the distribution of etiologies of renal artery stenosis (RAS) is scant in both Western countries and China. We retrospectively analyzed the etiology of RAS in 2047 consecutive inpatients diagnosed with RAS for hypertension at Fuwai Hospital between 1999 and 2014. The number of patients with atherosclerosis was 1668 (81.5%), 259 (12.7%) with Takayasu's arteritis (TA), 86 (4.2%) with fibromuscular dysplasia (FMD), 34 (1.6%) with other causes. There was an obvious increase with age in the proportion of atherosclerotic RAS (P<0.001). In patients aged ⩽40 years (n=319) the predominant etiology of RAS was TA (60.5%), followed by FMD (24.8%). In patients aged >40 years (n=1728) the major cause of RAS was atherosclerosis (94.7%), followed by TA (3.8%).The proportion of TA and FMD in female patients was significantly higher than that in male patients (P<0.001). In female patients aged ⩽40 years (n=215), the top three etiologies of RAS were TA (68.4%), FMD (27.9%) and atherosclerosis (1.4%). The present analysis showed that atherosclerosis, TA and FMD were sequentially the top three causes of RAS in the National Center of China. Age and gender had a significant effect on the distribution of etiologies of RAS.

Effect of sophoridine on Ca²âº induced Ca²âº release during heart failure.

Sophoridine is a type of alkaloid extract derived from the Chinese herb Sophora flavescens Ait (kushen) and possess a variety of pharmacological effects including anti-inflammation, anti-anaphylaxis, anti-cancer, anti-arrhythmic and so on. However, the effect of sophoridine on heart failure has not been known yet. In this study, the effect of sophoridine on heart failure was investigated using Sprague-Dawley (SD) rat model of chronic heart failure. Morphological results showed that in medium and high dose group, myofilaments were arranged orderly and closely, intermyofibrillar lysis disappeared and mitochondria contained tightly packed cristae compared with heart failure group. We investigated the Ca(2+) induced Ca(2+) transients and assessed the expression of ryanodine receptor (RyR2) and L-type Ca(2+) channel (dihydropyridine receptor, DHPR). We found that the cytosolic Ca(2+) transients were markedly increased in amplitude in medium (deltaF/F(0)=43.33+/-1.92) and high dose groups (deltaF/F(0)=47.21+/-1.25) compared with heart failure group (deltaF/F(0)=16.7+/-1.29, P<0.01), Moreover, we demonstrated that the expression of cardiac DHPR was significantly increased in medium- and high dose-group compared with heart failure rats. Our results suggest that sophoridine could improve heart failure by ameliorating cardiac Ca(2+) induced Ca(2+) transients, and that this amelioration is associated with upregulation of DHPR.

Cancer stem cells: targeting tumors at the source.

The cancer stem cell hypothesis states that tumors rely exclusively on the continued proliferation of a subset of cancer cells that originated from normal adult stem cells. These cells have two key traits: multipotency, and self-renewal. The prolonged lifespan of stem cells makes them perfect candidates for the accumulation of carcinogenic mutations that would convert them into cancer stem cells (CSCs) no longer responsive to the many regulatory pathways in place that are responsible for tight governance of proliferation and differentiation in normal stem cells. Comprehending what these regulatory pathways are, and how their derailment contributes to oncogenic transformation, can hold the key to finding new strategies to target CSCs in order to effectively treat cancer. Additionally, what environmental factors are involved in promoting or suppressing CSC tumorigenicity requires attention. The possibility that some cancers may have clonal origins in non-stem cell populations that were able to acquire stem cell-like properties, and the lack of complete cell autonomy in carcinogenesis, suggests that the CSC hypothesis is continually evolving. Continued research in this field can shed light on how effective selective elimination of CSCs as opposed to generalized targeting of cancer cells will be in the treatment of cancer.

Hematopoietic stem cells: cancer involvement and myeloid leukemia.

Hematopoietic stem cells (HSCs) are rare multipotent cells that possess ability to self-renew and differentiate to progenitor cells, which give rise to all blood cell lineages. The process involves specific regulation of gene transcription and its deregulation resulting in imbalance between self-renew and differentiation, can lead to cellular transformation and cancers. Substantial evidence indicates that accumulated mutations in HSCs contribute to the initiation and pathogenesis of at least some hematopoietic cancers. In particular, myeloid leukemias have been extensively characterized with regard to HSC and progenitor involvement. Thus, as a focal point for scientific and therapeutic endeavours, formation of cancer cells from HSCs represents a critical area of investigation. Consequently, understanding how HSCs function and how they undergo to transformation, is of fundamental importance to get insight in their contribution to the hematopoietic cancer development.

Pathways involved in the evolution of leukemic stem cells.

Understanding the evolution of the cancer cell from a normal cell holds the key to developing novel, potent therapies against cancer. Two hypotheses describing the origins of cancer cells have been developed: one stating that any normal cell can acquire the ability to replicate indefinitely and evade natural cell death signals by accumulating multiple mutations over time, and a second suggesting that adult stem cells, by virtue of their pre-existing capacity for differentiation, asymmetric division and self-renewal, are the more likely targets of carcinogenic mutation. The leukemic stem cell (LSC) was the first cancer stem cell described. Evolving from the aberrant regulation and mutation of hematopoietic stem cells (HSCs), LSCs are suggested to encompass the subset of tumor cells sufficient for continued tumorigenesis. LSCs were also found to differentiate into a variety of cancer cell progenitors in a manner reminiscent of HSC differentiation, also explaining the observed heterogeneity of leukemic cells. How these cells form from HSCs remains to be fully comprehended. However, over recent years, marked progress has been made in contributing to our knowledge of cancer stem cells and what signaling cascades are involved in their development. Therapeutics targeting the pathways allowing for LSCs to sustain proliferation and self-renewal may prove to be more effective treatments for lymphoblastic leukemia.

Estrogen combined with progesterone decreases cell proliferation and inhibits the expression of Bcl-2 via microRNA let-7a and miR-34b in ovarian cancer cells

PURPOSE: This study evaluated the effect of estrogen (E2), progesterone (P4), and the combination of them (E2 + P4) on survival rate, apoptosis, and the expressions of Bcl-2, hsa-let-7a and has-miR-34b in primary ovarian cancer cells to provide new clues for the clinical treatments of ovarian cancer. METHODS: The primary ovarian cancer cells from 60 cases of clinical ovarian cancer tissues were isolated and then cultured. The survival rate of ovarian cancer cells after the treatment of E2, P4 and E2 + P4 was analyzed by MTT assay. Cell apoptosis rate and cell cycle were measured by FACS analysis. Moreover, the relative abundance of Bcl-2 and microRNAs (let-7a, miR-34b) expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS: Low concentrations of estrogen (10(-10), 10(-8), 10(-6 )mol/L) did not affect the proliferation of ovarian cancer cells. However, the high concentration of estrogen (10(-4 )mol/L) inhibited survival rate of ovarian cancer cells. Progesterone (10(-4 )mol/L) inhibited the proliferation of cancer cells. The combination of estrogen and progesterone significantly inhibited the survival rate of ovarian cancer cells with a time- and dose-dependent manner. High concentration of estrogen combined with progesterone (E2 + P4) induced apoptosis of ovarian cancer cells. E2 + P4 promoted the expression of let-7a and miR-34b and reduced the expression of Bcl-2 in ovarian cancer cells. When the expression of let-7a or/and miR-34b was inhibited using miRNA inhibitors, E2 + P4 treatment did not change the protein level of Bcl-2. CONCLUSION: E2 + P4 significantly inhibited the cell survival, promoted the cell apoptosis, induced the expression of let-7a and miR-34b, and reduced the expression of Bcl-2 in ovarian cancer cells (AU)

No disponible

An SLE patient with prolactinoma and recurrent granulomatous mastitis successfully treated with hydroxychloroquine and bromocriptine.

Granulomatous mastitis (GM) is a rare benign mammary lesion in which autoimmunity and hyperprolactinemia are considered possible etiological factors. GM has a high frequency of relapse and may lead to chronic ulceration and fistula if not treated properly. Here we report a case of a 22-year-old systemic lupus erythematosus (SLE) patient with three years' disease duration, stable on prednisone and hydroxychloroquine, who was found to have prolactinoma and recurrent GM after she discontinued medication on her own accord. The patient subsequently recovered and remained free of GM relapse under treatment of prednisone, hydroxychloroquine and bromocriptine. Though autoimmune disorders and prolactinoma were reported in GM, a coexisting condition of SLE, prolactinoma, and granulomatous mastitis has rarely been observed in one patient. We suggest our case as an illustrative example of the complex interaction between autoimmunity, neuroendocrine dysfunction, and manifestations in the breast: Immunological disturbances in the background of SLE, coupled with elevated prolactin levels secondary to a prolactinoma, may have predisposed the patient to the development of GM. The mammary lesion recovered and maintained free of relapse under immunosuppressive and antiprolactinemic therapy.

Perivascular epithelioid cell tumor of the liver: a case report and literature review.

Perivascular epithelioid cell tumors (PEComas) are mesenchymal tumors containing variable component of smooth muscles, fat and vessels. They occured pretty rare in the liver and no characteristic of imaging data have been demonstrated up to now. We herein present a case of a 58-year-old man with a hepatic PEComa which was correct diagnosed through immunohistochemical confirmation with HMB-45. The clinicopathological and imaging features of hepatic PEComa were analyzed retrospectively. This is the first paper which demonstrated the characteristic of imaging data among liver PEComas and other liver lesions. However, the diagnostic criteria of PEComa depends on pathology. Hepatectomy is the effective treatment.

Menin mediates epigenetic regulation via histone H3 lysine 9 methylation.

Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor that leads to multiple endocrine tumors upon loss of its function. Menin functions as a transcriptional activator by tethering MLL complex to mediate histone H3 K4 methylation. It also functions as a repressor. However, the molecular mechanism of how menin contributes to the opposite outcome in gene expression is largely unknown. Here, we investigated the role of menin in the epigenetic regulation of transcription mediated by histone covalent modification. We show that the global methylation level of histone H3 K9, as well as H3 K4, was decreased in Men1(-/-) MEF cells. Consistently, menin was able to interact with the suppressor of variegation 3-9 homolog family protein, SUV39H1, to mediate H3 K9 methylation. This interaction decreased when patient-derived MEN1 mutation was introduced into the SUV39H1-interaction domain. We show that menin mediated different chromatin changes depending on target genes. Chromatin immunoprecipitation studies showed that menin directly associated with the GBX2 promoter and menin-dependent recruitment of SUV39H1 was essential for chromatin remodeling and transcriptional regulation. These results provide a molecular basis of how menin functions as a transcriptional repressor and suggest that menin-dependent integration of H3 K9 methylation might play an important role in preventing tumors.

Statin administration does not improve the mobilization of very small embryonic-like stem cells (VSELs) in contrast to resveratrol treatment in a murine model of acute myocardial infarction.

We have found that short-term statin treatment plus stem cell transplantation in acutely infarcted hearts improves cardiac function because statins promote the efficacy of cellular cardiomyoplasty. Autologous Sca-1(+)Lin(-)CD45(-)(CXCR(+)) very small embryonic-like stem cell (VSEL) mobilization in acute myocardial infarction (AMI) correlates with the preservation of cardiac function. Whether short-term atorvastatin (Ator) can enhance the mobilization or recruitment of VSELs in AMI is still unclear. We divided mice into 4 groups: 1) sham; 2) AMI; 3) AMI+resveratrol (RSV) as a positive control; and 4) AMI+Ator. There was an increase in the circulating VSEL/full population of leukocytes (FPL) ratio 48 hours after AMI, and AMI+RSV increased it further. Ator administration did not increase the VSEL/FPL ratio. The cardiac stromal cell-derived factor-1 (SDF-1) and SDF-1alpha levels were in agreement with the results of VSEL mobilization. One week after AMI, more Sca-1(+)CXCR(+) cells were recruited to the myocardium of AMI+RSV mice but not AMI+Ator mice. Short-term Ator administration failed to upregulate cardiac SDF-1 and could not enhance the recruitment of VSELs early after AMI.

Surgical consideration of in situ prosthetic replacement for primary infected abdominal aortic aneurysms.

OBJECTIVES: To review our surgical experience of primary infected abdominal aortic aneurysms, with the aim of assessing the safety and durability of in situ prosthetic replacement. DESIGN: Retrospective study in a university hospital. MATERIALS AND METHODS: Thirty-four patients who underwent surgery for primary infected abdominal aortic aneurysms over the past 18 years were reviewed. Operative details and outcomes were recorded for analysis. RESULTS: There were six suprarenal and 28 infrarenal infections. Salmonellae (18 patients) were the most common pathogens. Thirty patients underwent in situ prosthetic replacement, two underwent extra-anatomic bypass and two underwent endovascular repair. The surgical mortality for overall patients was 18%, and for patients reconstructed in situ, 17%. Among the 30 patients reconstructed in situ, four patients who underwent concomitant gastrointestinal procedures (e.g., repair of the duodenal defect) died. By contrast, 25 of 26 patients without gastrointestinal involvement survived surgery. After a median follow-up period of 58 months, two discharged patients who underwent in situ reconstruction died of late graft infection. CONCLUSIONS: Our experience suggests that in situ prosthetic replacement can be performed safely with durable outcomes in the majority of patients with infected abdominal aortic aneurysms. Nevertheless, we advise caution when considering this technique with concomitant gastrointestinal procedures.