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Find video protocols related to scientific articles indexed in Pubmed.
Phyllanthus urinaria induces mitochondrial dysfunction in human osteosarcoma 143B cells associated with modulation of mitochondrial fission/fusion proteins.
Mitochondrion
PUBLISHED: 04-14-2014
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Phyllanthus urinaria (P. urinaria), a widely used herbal medicine, has been reported to possess various biological characteristics including anti-inflammation, anti-virus, anti-bacteria, anti-hepatotoxicity and anti-cancer. This study provides molecular evidence associated with the dynamics and organization of mitochondria in osteosarcoma 143B cells resulted from P urinaria. Herein, P. urinaria-induced cytotoxicity and ROS associated with the inhibition of mitochondrial membrane potential were reversed by N-acetylcysteine (NAC). The endogenous antioxidant enzymes such as manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX1) were activated by P. urinaria, but not correlated to catalase. P. urinaria decreased mitochondrial respiration activity as well as respiratory chain enzymes and HIF-1? in osteosarcoma 143B cells. Additionally, both adenosine triphosphate (ATP) synthase activation and ATP production were suppressed by P. urinaria. We further investigated changes of mitochondrial dynamic in osteosarcoma 143B cells. P. urinaria indeed fragmented the mitochondrial network of osteosarcoma 143B cells. We found a significant decrease in optic atrophy type 1 (Opa1) and mitofusin 1 (Mfn1) related to fusion proteins as well as increase mitochondrial fission 1 protein (Fis1) related to fission protein. It indicated that P. urinaria modulated the mitochondrial dynamics via fusion and fission machinery. Altogether, this study offers the evidence that mitochondrial dysfunction with dynamic change is essential components for the anti-cancer mechanism elicited by P. urinaria.
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Resveratrol partially prevents rotenone-induced neurotoxicity in dopaminergic SH-SY5Y cells through induction of heme oxygenase-1 dependent autophagy.
Int J Mol Sci
PUBLISHED: 01-08-2014
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Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons. Mitochondrial dysfunction, oxidative stress or protein misfolding and aggregation may underlie this process. Autophagy is an intracellular catabolic mechanism responsible for protein degradation and recycling of damaged proteins and cytoplasmic organelles. Autophagic dysfunction may hasten the progression of neuronal degeneration. In this study, resveratrol promoted autophagic flux and protected dopaminergic neurons against rotenone-induced apoptosis. In an in vivo PD model, rotenone induced loss of dopaminergic neurons, increased oxidation of mitochondrial proteins and promoted autophagic vesicle development in brain tissue. The natural phytoalexin resveratrol prevented rotenone-induced neuronal apoptosis in vitro, and this pro-survival effect was abolished by an autophagic inhibitor. Although both rotenone and resveratrol promoted LC3-II accumulation, autophagic flux was inhibited by rotenone and augmented by resveratrol. Further, rotenone reduced heme oxygenase-1 (HO-1) expression, whereas resveratrol increased HO-1 expression. Pharmacological inhibition of HO-1 abolished resveratrol-mediated autophagy and neuroprotection. Notably, the effects of a pharmacological inducer of HO-1 were similar to those of resveratrol, and protected against rotenone-induced cell death in an autophagy-dependent manner, validating the hypothesis of HO-1 dependent autophagy in preventing neuronal death in the in vitro PD model. Collectively, our findings suggest that resveratrol induces HO-1 expression and prevents dopaminergic cell death by regulating autophagic flux; thus protecting against rotenone-induced neuronal apoptosis.
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A NEW SIMPLIFIED ONE-PORT LAPAROSCOPIC TECHNIQUE FOR PERITONEAL DIALYSIS CATHETER PLACEMENT.
Perit Dial Int
PUBLISHED: 10-01-2013
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Various techniques for laparoscopic insertion of a peritoneal dialysis catheter have been described. Usually 2 - 3 ports are required, and complications related to the port sites (such as abdominal wall hernia, leakage, and hemorrhage) cannot be avoided. To minimize the potential complications, we designed a simplified 1-port laparoscopic technique for peritoneal dialysis catheter placement.
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Associations of mitochondrial haplogroups b4 and e with biliary atresia and differential susceptibility to hydrophobic bile Acid.
PLoS Genet.
PUBLISHED: 08-01-2013
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Mitochondrial dysfunction has been implicated in the pathogenesis of biliary atresia (BA). This study aimed to determine whether a specific mitochondrial DNA haplogroup is implicated in the pathogenesis and prognosis of BA. We determined 40 mitochondrial single nucleotide polymorphisms in 15 major mitochondrial haplogroups by the use of 24-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes in 71 patients with BA and in 200 controls in the Taiwanese population of ethnic Chinese background. The haplogroup B4 and E prevalence were significantly lower and higher respectively, in the patients with BA than in the controls (odds ratios, 0.82 [p = 0.007] and 7.36 [p = 0.032] respectively) in multivariate logistic-regression analysis. The 3-year survival rate with native liver was significantly lower in haplogroup E than the other haplogroups (P = 0.037). A cytoplasmic hybrid (cybrid) was obtained from human 143B osteosarcoma cells devoid of mtDNA (?(0) cell) and was fused with specific mtDNA bearing E and B4 haplogroups donated by healthy Taiwanese subjects. Chenodeoxycholic acid treatment resulted in significantly lower free radical production, higher mitochondrial membrane potential, more viable cells, and fewer apoptotic cybrid B4 cells than parental 143B and cybrid E cells. Bile acid treatment resulted in a significantly greater protective mitochondrial reaction with significantly higher mitochondrial DNA copy number and mitofusin 1 and 2 concentrations in cybrid B4 and parental cells than in cybrid E cells. The results of the study suggested that the specific mitochondrial DNA haplogroups B4 and E were not only associated with lower and higher prevalence of BA respectively, in the study population, but also with differential susceptibility to hydrophobic bile acid in the cybrid harboring different haplogroups.
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Dislodgement of port-A catheters in pediatric oncology patients: 11 years of experience.
World J Surg Oncol
PUBLISHED: 03-30-2013
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Port-A catheters are frequently used in pediatric cancer patients. Their dislodgement is potentially seriously risky although the incidence is not high. We analyzed our 11 years of data to address this important problem.
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Study of insulin resistance in cybrid cells harboring diabetes-susceptible and diabetes-protective mitochondrial haplogroups.
Mitochondrion
PUBLISHED: 01-27-2013
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This study aims to elucidate the independent role of mitochondria in the pathogenesis of insulin resistance (IR).
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Toll-like receptor 3 expression inhibits cell invasion and migration and predicts a favorable prognosis in neuroblastoma.
Cancer Lett.
PUBLISHED: 01-27-2013
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To evaluate the clinical significance of TLR3 expression on neuroblastomas, we performed immunohistochemical study on archival tissues and in vitro studies on neuroblastoma cell lines. The results showed that positive TLR3 expression was associated with favorable histology and prognosis. Activation of TLR3 by polyinosinic:polycytidylic acid [poly(I:C)] treatment is effective to suppress cell migration and invasion and to decrease organized assembly of F-actin and filopodia formation, in TLR3-expressing SK-N-AS cells, which could be reversed by TLR3-targeting siRNA treatment. TLR3 agonist poly(I:C) promotes GAP-43 expression also in SK-N-AS cells only. Taken together, TLR3 could serve to predict favorable behavior in neuroblastomas.
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2-Deoxyglucose treatment complements the cisplatin- or BH3-only mimetic-induced suppression of neuroblastoma cell growth.
Int. J. Biochem. Cell Biol.
PUBLISHED: 01-09-2013
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Neuroblastoma (NB) is characterized by pleomorphic molecular characteristics, which may influence cellular metabolism as well as the efficacy of glycolytic inhibitors in suppressing NB cell growth. We studied the metabolic profile of four NB cell lines without or with MYCN amplification and found no unanimous metabolic characteristics. The two NB cell lines with MYCN amplification exhibited a significantly higher HIF-1? expression level and ATP content compared to the two cell lines without MYCN amplification. MYCN amplification was associated with significantly greater inhibition of cellular proliferation and more apoptosis after treatment with the glycolytic inhibitor 2-deoxyglucose (2DG). Further analysis showed that 2DG increased PDK1 but decreased the ATP content and increased expression of the proapoptotic BH3-only protein Bad in both SK-N-AS (without MYCN amplification) and SK-N-DZ (with MYCN amplification) cells. In addition, 2DG decreased hexokinase II expression in SK-N-DZ cells and increased HIF-1?, Noxa, and PUMA expression in SK-N-AS cells. Pretreating SK-N-DZ cells with 2DG or cisplatin for 24 h, followed by cisplatin or 2DG for another 24 h, resulted in significantly greater suppression of cellular proliferation compared to treatment with 2DG or cisplatin for 48 h alone. Effective suppression of SK-N-AS proliferation occurred only when the cells were pretreated with cisplatin. Pretreatment of SK-N-DZ, but not SK-N-AS, with 2DG followed by the BH3-only mimetic ABT737 also resulted in significantly greater suppression of cellular proliferation compared to treatment with ABT737 or 2DG alone. A low dose of 2DG (2mM) was as effective as a high dose (20mM) in SK-N-DZ cells. In conclusion, the glycolytic inhibitor 2DG complemented the cisplatin- or ABT737-induced suppression of growth in NB cells, which are sensitive to glycolytic inhibition.
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Toll-like receptor 3-mediated tumor invasion in head and neck cancer.
Oral Oncol.
PUBLISHED: 08-01-2011
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Chronic inflammation associated with some infectious agents can lead to cancer. The Toll-like receptor (TLR) family is one of the largest and best-studied families of pathogen-associated molecular patterns. TLR3 recognizes double-stranded RNA and is a major effector of the immune response against viral pathogens.
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Differential toll-like receptor 3 (TLR3) expression and apoptotic response to TLR3 agonist in human neuroblastoma cells.
J. Biomed. Sci.
PUBLISHED: 05-12-2011
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Toll-like receptor-3 (TLR-3) is a critical component of innate immune system against dsRNA viruses and is expressed in the central nervous system. However, it remains unknown whether TLR3 may serve as a therapeutic target in human neuroblastoma (NB).
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Academic achievements of doctors who studied at a domestic institute for clinical medicine.
Chang Gung Med J
PUBLISHED: 05-05-2011
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The purpose of this study was to investigate the outcomes of doctors who studied at a graduate degree program at a domestic institute for clinical medicine.
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Pediatric malignant ovarian tumors: 15 years of experience at a single institution.
Pediatr Neonatol
PUBLISHED: 04-12-2011
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Malignant ovarian tumors in children are relatively rare. We reviewed our 15-year experience to understand their clinical presentations, managements, and prognoses.
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Severity of lens opacity, age, and correlation of the level of silent information regulator T1 expression in age-related cataract.
J Cataract Refract Surg
PUBLISHED: 01-31-2011
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To evaluate the correlation between the severity of lens opacity, patient age, and the level of silent information regulator T1 (SirT1) expression in the lens epithelium of age-related cataracts.
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Dexamethasone decreases cholestatic liver injury via inhibition of intrinsic pathway with simultaneous enhancement of mitochondrial biogenesis.
Steroids
PUBLISHED: 01-31-2011
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Mitochondria are known to be involved in cholestatic liver injury. We tested the hypothesis that glucocorticoids can modulate mitochondrial function to alleviate cholestatic liver injury.
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Isolated gastric varices with upper gastrointestinal bleeding 11 years after distal pancreatectomy for ruptured pancreatic pseudocyst.
J. Pediatr. Surg.
PUBLISHED: 01-18-2011
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Isolated gastric varices with upper gastrointestinal bleeding are an unusual event, particularly in children in whom obstruction of the splenic vein is an infrequent occurrence. We describe a 19-year-old man with bleeding isolated gastric varices 11 years after he underwent distal pancreatectomy with preservation of the spleen for a ruptured pancreatic pseudocyst. The disorder was cured with splenectomy.
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Glucocorticoid modulates high-mobility group box 1 expression and Toll-like receptor activation in obstructive jaundice.
J. Surg. Res.
PUBLISHED: 01-17-2011
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Obstructive jaundice is associated with bacterial translocation and inflammatory cytokine induction. It is unknown if toll-like receptors (TLRs) and their upstream molecule high mobility group box-1 (HMGB1) are involved in the pathogenetic mechanism and if glucocorticoid is effective in modulating the process.
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Endotoxin and CD14 in the progression of biliary atresia.
J Transl Med
PUBLISHED: 10-13-2010
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Biliary atresia (BA) is a typical cholestatic neonatal disease, characterized by obliteration of intra- and/or extra-hepatic bile ducts. However, the mechanisms contributing to the pathogenesis of BA remain uncertain. Because of decreased bile flow, infectious complications and damaging endotoxemia occur frequently in patients with BA. The aim of this study was to investigate endotoxin levels in patients with BA and the relation of these levels with the expression of the endotoxin receptor, CD14.
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Late-presenting congenital diaphragmatic hernia in childhood.
Acta Paediatr.
PUBLISHED: 10-08-2010
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To characterize the clinical manifestations of late-presenting diaphragmatic hernia and its associated anomalies, diagnostic methods and outcomes.
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Huge pelvi-abdominal malignant inflammatory myofibroblastic tumor with rapid recurrence in a 14-year-old boy.
World J. Gastroenterol.
PUBLISHED: 06-03-2010
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Inflammatory myofibroblastic tumor (IMT) is an uncommon benign neoplasm with locally aggressive behavior but malignant change is rare. We report an unusual case of pelvic-abdominal inflammatory myofibroblastic tumor with malignant transformation in a 14-year-old boy presenting with abdominal pain and 9 kg body weight loss in one month. Computed tomography revealed a huge pelvi-abdominal mass (30 cm), possibly originating from the pelvic extraperitoneal space, protruding into the abdomen leading to upward displacement of the bowel loops, downward displacement of the urinary bladder, massive central necrosis, a well-enhanced peripheral solid component with prominent peritumoral vascularity. Subsequent examination confirmed the computed tomographic findings. Histopathologic examination revealed proliferative epitheloid and spindle cells, inflammatory cell infiltration and high mitotic counts. Immunohistochemistry was strongly positive for anaplastic lymphoma kinase and revealed a high proliferative index (ki-67 = 40%). DNA sequencing and electronic microscopy further confirmed the primitive fibroblastic cell phenotype of the tumor and a final diagnosis of inflammatory myofibroblastic tumor with malignant transformation was established. Rapid tumor recurrence was noted 20 d after radical tumor resection. To our knowledge, this is the largest documented case of IMT in a pediatric patient and the first report of IMT with malignant transformation originating from the pelvic extraperitoneal space.
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Transumbilical laparoscopic appendectomy for acute appendicitis: a reliable one-port procedure.
Surg Endosc
PUBLISHED: 03-03-2010
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Emergency surgical procedures frequently must be performed at times when availability of adequately trained personnel is problematic yet the requirements for maintaining surgical quality and patient safety remain unchanged. This report aims to describe a safe, effective, transumbilical, one-port laparoscopic technique for appendectomy that can be performed by one surgeon.
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Mitochondrial dysfunction and biogenesis in the pathogenesis of Parkinsons disease.
Chang Gung Med J
PUBLISHED: 12-29-2009
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Parkinsons disease (PD) is a progressive neurological disorder marked by nigrostriatal dopaminergic degeneration and development of cytoplasmic aggregates known as Lewy bodies. The impact of this disease is indicated by the fact that mortality is two to five times as high among affected persons as among age-matched controls. However, the cause of PD is still unknown and no cure is available at present. Several biochemical abnormalities have been described in the brains of patients with PD, including oxidative stress and mitochondrial dysfunction. Recent identification of specific gene mutations that cause PD has further reinforced the relevance of oxidative stress and mitochondrial dysfunction in the familial and sporadic forms of the disease. The proteins that are reported to be related to familial PD-PTEN-induced putative kinase 1 (PINK1), DJ-1, alpha- synuclein, leucine-rich repeat kinase 2 (LRRK2), and, possibly, parkin-are either mitochondrial proteins or are associated with mitochondria, and all are involved in pathways that elicit oxidative stress or free radical damage. Mitochondria are continually exposed to reactive oxygen species and accumulate oxidative damage more rapidly than the rest of the cell. Therefore, Parkinsons disease has been suggested to be associated with mitochondrial dysfunction. Since mitochondria are the major intracellular organelles that regulate both cell survival and death, clarifying the involvement of mitochondrial dysfunction and biogenesis during the process of PD could provide treatment strategies that might successfully intervene in the pathogenesis and slow the progression of the disease.
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Cholestasis downregulate hepcidin expression through inhibiting IL-6-induced phosphorylation of signal transducer and activator of transcription 3 signaling.
Lab. Invest.
PUBLISHED: 08-03-2009
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Hepcidin is downregulated during progressive cholestasis in biliary atresia, but the mechanism is unknown. To verify whether downregulation of hepcidin is specific to cholestasis irrespective of the patients age, we first analyzed liver hepcidin mRNA and protein expression in adults with primary biliary cirrhosis (PBC) (n=4), non-cholestatic cirrhosis (n=19) and in controls (n=9). We evaluated the tyrosine phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) expressions in the liver sections. A rat model of cholestasis by ligation of the extrahepatic bile duct (BDL) was created, and lipopolysaccharide (LPS)-induced cholangitis in cholestatic rats 2 weeks after BDL was also established to study the modulation of hepcidin by interleukin-6 (IL-6) and STAT3 signaling pathway in these models, using real-time quantitative reverse transcription-PCR, immunohistochemistry, western blotting and enzyme-linked immunosorbent assay (ELISA). An in vitro study of the effect of bile acids on hepcidin expression was carried out to re-confirm the in vivo findings. There was significantly lower hepcidin mRNA and pSTAT3 protein expression in cholestatic cirrhosis compared with non-cholestatic cirrhosis in adults. BDL caused significant decrease in hepcidin and gp130 mRNA expression compared with sham-operated group and normal control. Furthermore, there was significantly lower pSTAT3 protein expression and nuclear translocation in the cholestatic liver from the patients and the BDL rats, which was comparable to lower liver hepcidin mRNA and plasma hepcidin expression. Furthermore, BDL for 2 weeks attenuated the upregulation of hepcidin expression induced by LPS. Hydrophobic bile acid glycochenodeoxycholate inhibited IL-6-induced pSTAT3 expression in primary hepatocytes and resulted in the downregulation of hepcidin mRNA expression. In conclusion, the study shows that cholestasis or its important component-hydrophobic bile acids-can downregulate hepcidin expression through inhibiting IL-6-induced STAT3 phosphorylation and pSTAT3 protein nuclear translocation.
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Early transcriptional deregulation of hepatic mitochondrial biogenesis and its consequent effects on murine cholestatic liver injury.
Apoptosis
PUBLISHED: 05-23-2009
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Mitochondria are known to be involved in cholestatic liver injury, but the damage and biogenesis of mitochondria in response to the early stage of cholestasis is unknown. A rat model of cholestasis was established by bile duct ligation (BDL), with simultaneous creation of the sham group receiving laparotomy without BDL. A significant decrease of liver peroxisome proliferators-activated receptor gamma coactivator-1alpha, mitochondrial transcriptional factor A (Tfam) and glutathione peroxidase (GPx) mRNA and Tfam protein from 6 to 72 h after BDL was found, which was associated with significant decrease of the glutathione, GPx and catalase activity at 72 h. At 72 h after BDL, mitochondrial DNA copy number reached the lowest level, while caspase 9 and 3 activity, but not caspase 8, Bax, Bcl(2), Fas L and Fas-Fas L complex, were upregulated significantly in the liver homogenates of BDL rats. The apoptotic liver cells appeared in large amounts in the rat liver by 72 h after BDL. Our results indicate that transcriptional regulation of the mitochondrial biogenesis is impaired within a few hours after complete bile duct obstruction, resulting in later mitochondrial dysfunction and consequent cholestatic liver injury via the intrinsic apoptosis pathway.
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Patterns of hepatoblastoma and hepatocellular carcinoma in children after universal hepatitis B vaccination in taiwan: a report from a single institution in southern Taiwan.
J. Pediatr. Hematol. Oncol.
PUBLISHED: 02-06-2009
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To retrospectively evaluate clinical features, treatment, and outcome of patients with hepatoblastoma (HB) and hepatocellular carcinoma (HCC).
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Tau proteins in serum predict outcome after severe traumatic brain injury.
J. Surg. Res.
PUBLISHED: 01-10-2009
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The identification of reliable outcome predictors after traumatic brain injury (TBI) is crucial. The objective of our study was to investigate the role of tau protein as a serum marker of TBI.
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The creation of cybrids harboring mitochondrial haplogroups in the Taiwanese population of ethnic Chinese background: an extensive in vitro tool for the study of mitochondrial genomic variations.
Oxid Med Cell Longev
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Mitochondrial DNA (mtDNA) haplogroups may contribute to the development of aging-related diseases. A reliable in vitro cellular system for investigating the physiologic significance of mtDNA haplogroups is essential. This study aims to construct and characterize a series of cybrid cell lines harboring variant mtDNA haplogroups collected from healthy Taiwanese volunteers. Cybrid cells harboring different mtDNA haplogroups like B4a, B4b, B4c, B4d, B5, R, F1a, F2, D4e, D4a, D5b, D5a, E, M8, C, and N9a were prepared. Luminex 1000 and full-length mtDNA sequencing were used to confirm that mtDNA haplogroups of transmitochondrial cybrids were identical to their original donors. Cybrid B4b had a significantly lower oxygen consumption rate and higher mitochondrial membrane potential compared to F1a, B5, D5a, D4a, and N9a but had more susceptibility to H(2)O(2)-induced oxidative stress than cybrid F1a, D4a, and N9a. Cybrid N9a had better oxygen consumption and H(2)O(2)-challenged viability compared to B4b, F1a, B5, D5a, and D4a. A series of cybrid cells harboring the main haplogroups of the Taiwanese population with ethnic Chinese background has been developed in vitro. With this mtDNA haplogroup population, the underlying mechanisms of aging-related diseases may be better understood, and therapeutic interventions can be accelerated.
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Expression of Toll-like receptor9 in diffuse large B-cell lymphoma: further exploring CpG oligodeoxynucleotide in NF?B pathway.
APMIS
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Human Toll-like receptors (TLRs) that recognize a variety of pathogen-associated molecular patterns are associated with activation and immunogenic response in lymphoid neoplasms, but rarely explored in diffuse large B-cell lymphoma (DLBCL). We conducted this study to evaluate the expression of TLR9 in and potential treatment of DLBCL with TLR9 agonist - CpG oligodeoxynucleotide (ODN). The real-time quantitative reverse transcription-polymerase chain reaction was carried out to detect TLR9 expression in 41 formalin-fixed paraffin-embedded samples. The transformation of immunophenotype and NF?B pathway of DLBCL upon CpG ODN stimulation were investigated by a DLBCL cell line. TLR9 was commonly detected in DLBCL with relative mRNA levels above 1.0 × 10(-2) in 35 of 41 cases (85.36%). It was suspected that a high proportion of DLBCL to be activated by CpG stimulation. In vitro study with a DLBCL cell line revealed an increased CD20, but decreased BCL-6 and MUM1/IRF4 expression after treatment with CpG ODN. The NF?B pathway was initially activated, but finally suppressed upon CpG ODN stimulation. The proliferation of tumor cells was also inhibited by long time incubation. These findings provide new insights into the role of TLR9 in DLBCL and potential implication of TLR9 agonist in the treatment of DLBCL.
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Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes.
Diabetes
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Both the coding and control regions of mitochondrial DNA (mtDNA) play roles in the generation of diabetes; however, no studies have thoroughly reported on the combined diabetogenic effects of variants in the two regions. We determined the mitochondrial haplogroup and the mtDNA sequence of the control region in 859 subjects with diabetes and 1,151 normoglycemic control subjects. Full-length mtDNA sequences were conducted in 40 subjects harboring specific diabetes-related haplogroups. Multivariate logistic regression analysis with adjustment for age, sex, and BMI revealed that subjects harboring the mitochondrial haplogroup B4 have significant association with diabetes (DM) (odds ratio [OR], 1.54 [95% CI 1.18-2.02]; P < 0.001), whereas subjects harboring D4 have borderline resistance against DM generation (0.68 [0.49-0.94]; P = 0.02). Upon further study, we identified an mtDNA composite group susceptible to DM generation consisting of a 10398A allele at the coding region and a polycytosine variant at nucleotide pair 16184-16193 of the control region, as well as a resistant group consisting of C5178A, A10398G, and T152C variants. The OR for susceptible group is 1.31 (95% CI 1.04-1.67; P = 0.024) and for the resistant group is 0.48 (0.31-0.75; P = 0.001). Our study found that mtDNA variants in the coding and control regions can have combined effects influencing diabetes generation.
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Reappraise the effect of redo-Kasai for recurrent jaundice following Kasai operation for biliary atresia in the era of liver transplantation.
Pediatr. Surg. Int.
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This study was conducted to reappraise the efficacy of redo-Kasai (or revision) in the era of liver transplantation as a treatment option in those patients with recurrent jaundice after initially successful Kasai procedure.
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Transumbilical 1-port laparoscopic resection of benign ovarian tumor.
J. Pediatr. Surg.
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We evaluated the effectiveness of transumbilical 1-port laparoscopic resection of benign ovarian tumors in children with limited working space.
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Selective activation of Toll-like receptor 7 in activated hepatic stellate cells may modulate their profibrogenic phenotype.
Biochem. J.
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Cholestatic liver injury may activate HSCs (hepatic stellate cells) to a profibrogenic phenotype, contributing to liver fibrogenesis. We have previously demonstrated the involvement of TLR (Toll-like receptor) 7 in the pathogenesis of biliary atresia. In the present study we investigated the ability of TLR7 to modulate the profibrogenic phenotype in HSCs. Obstructive jaundice was associated with significant down-regulation of TLR7. Primary HSCs isolated from BDL (bile duct ligation) rats with obstructive jaundice exhibited reduced expression of TLR7 and increased expression of ?-SMA (?-smooth muscle actin) and collagen-?1 compared with sham rats, reflecting HSC-mediated changes. Treatment of primary activated rat HSCs and rat T6 cells with CL075, a TLR7 and TLR8 ligand, significantly decreased expression of MCP-1 (monocyte chemotactic protein-1), TGF-?1 (transforming growth factor-?1), collagen-?1 and MMP-2 (matrix metalloproteinase-2), and inhibited cell proliferation and migration. In contrast, silencing TLR7 expression with shRNA (short hairpin RNA) in T6 cells effectively blocked the effects of CL075 stimulation, reversing the changes in MCP-1, TGF-?1 and collagen-?1 expression and accelerating cell migration. Our results indicate that obstructive jaundice is associated with down-regulation of TLR7 and up-regulation of profibrogenic gene expression in HSCs. Selective activation of TLR7 may modulate the profibrogenic phenotype in activated HSCs associated with cholestatic liver injury.
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Toll-like receptor-4 agonist inhibits motility and invasion of hepatoblastoma HepG2 cells in vitro.
Pediatr Blood Cancer
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Expression of toll-like receptor-4 (TLR4) on tumor cells is known to mediate innate immune responses that influence tumor cell growth and migration. This study aimed to characterize TLR4 expression and elucidate its functional significance in human hepatoblastoma (HB) cells.
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Effects of hepatocyte CD14 upregulation during cholestasis on endotoxin sensitivity.
PLoS ONE
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Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia. We therefore propose that lipopolysacharides (LPS) may stimulate CD14 production in liver cells and promote the removal of endotoxins. The aims of this study are to test the hypothesis that CD14 is upregulated by LPS and investigate the pathophysiological role of CD14 production during cholestasis. Using Western blotting, qRT-PCR, and promoter activity assay, we demonstrated that LPS was associated with a significant increase in CD14 and MD2 protein and mRNA expression and CD14 promoter activity in C9 rat hepatocytes but not in the HSC-T6 hepatic stellate cell line in vitro. To correlate CD14 expression and endotoxin sensitivity, in vivo biliary LPS administration was performed on rats two weeks after they were subjected to bile duct ligation (BDL) or a sham operation. CD14 expression and endotoxin levels were found to significantly increase after LPS administration in BDL rats. These returned to basal levels after 24 h. In contrast, although endotoxin levels were increased in sham-operated rats given LPS, no increase in CD14 expression was observed. However, mortality within 24 h was more frequent in the BDL animals than in the sham-operated group. In conclusion, cholestasis and LPS stimulation were here found to upregulate hepatic CD14 expression, which may have led to increased endotoxin sensitivity and host proinflammatory reactions, causing organ failure and death in BDL rats.
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High-mobility group box 1 protein is implicated in advanced glycation end products-induced vascular endothelial growth factor A production in the rat retinal ganglion cell line RGC-5.
Mol. Vis.
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High-mobility group box 1 protein (HMGB1) has been reported to be a potent proangiogenic factor induced by inflammatory stress. In this study, we explore the role of HMGB1 in advanced glycation end products (AGEs)-induced vascular endothelial growth factor A (VEGF-A) production in rat retinal ganglion cell line 5 (RGC-5) cells.
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Hepcidin protects against lipopolysaccharide-induced liver injury in a mouse model of obstructive jaundice.
Peptides
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Obstructive jaundice (OJ) increases the risk of liver injury and sepsis, leading to increased mortality. Cholestatic liver injury is associated with a downregulation of hepcidin expression levels. In fact, hepcidin has an important antimicrobial effect, especially against Escherichia coli. It is unknown whether supplementing recombinant hepcidin is effective in alleviating cholestasis-induced liver injury and mortality in mice with superimposed sepsis. A mouse model of cholestasis was developed using extrahepatic bile duct ligation for 3 days. In addition, sepsis due to E. coli 0111:B4 lipopolysaccharide (LPS) was induced in the model. The serum levels of total bilirubin, AST, ALT, and LDH and the mRNA levels of IL-1?, TNF-?, and MCP-1 in the liver were significantly higher in the OJ mice receiving LPS than in the sham-operated mice receiving LPS. Compared to the OJ mice receiving LPS, the hepcidin-pretreated OJ mice receiving LPS showed a significant decrease in the above mentioned parameters, as well as a reversal in the downregulation of LC3B-II and upregulation of cleaved caspase-3; this, in turn, led to significantly decreased lethality in 24h. In conclusion, these results indicate that hepcidin pretreatment significantly reduced hepatic proinflammatory cytokine expression and liver injury, leading to reduced early lethality in OJ mice receiving LPS. Enhanced autophagy and reduced apoptosis may account for the protective effects of hepcidin.
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Phyllanthus urinaria Induces Apoptosis in Human Osteosarcoma 143B Cells via Activation of Fas/FasL- and Mitochondria-Mediated Pathways.
Evid Based Complement Alternat Med
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Phyllanthus urinaria (P. urinaria), in this study, was used for the treatment of human osteosarcoma cells, which is one of the tough malignancies with few therapeutic modalities. Herein, we demonstrated that P. urinaria inhibited human osteosarcoma 143B cells growth through an apoptotic extrinsic pathway to activate Fas receptor/ligand expression. Both intracellular and mitochondrial reactive oxygen species were increased to lead to alterations of mitochondrial membrane permeability and Bcl-2 family including upregulation of Bid, tBid, and Bax and downregulation of Bcl-2. P. urinaria triggered an intrinsic pathway and amplified the caspase cascade to induce apoptosis of 143B cells. However, upregulation of both intracellular and mitochondrial reactive oxygen species and the sequential membrane potential change were less pronounced in the mitochondrial respiratory-defective 143B?(0) cells compared with the 143B cells. This study offers the evidence that mitochondria are essential for the anticancer mechanism induced by P. urinaria through both extrinsic and intrinsic pathways.
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Inflammation-induced hepcidin is associated with the development of anemia and coronary artery lesions in Kawasaki disease.
J. Clin. Immunol.
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Kawasaki disease (KD) is a systemic febrile vasculitis complicated by coronary artery lesions (CAL). Anemia is common in patients with KD and is associated with a prolonged duration of active inflammation. Hepcidin is a central modulator of inflammation-associated anemia, acting via control of iron absorption and a direct inhibitory effect on erythropoiesis. The aims of this study were to investigate the role of inflammation-induced hepcidin in the development of anemia, the occurrence of CAL formation, and IVIG treatment response in patients with KD.
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Biphasic Response of Mitochondrial Biogenesis to Oxidative Stress in Visceral Fat of Diet-Induced Obesity Mice.
Antioxid. Redox Signal.
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Aims Studies in skeletal muscle demonstrate a strong association of mitochondrial dysfunction with insulin resistance (IR). However, there is still a paucity of knowledge regarding the alteration of mitochondria in adipose tissue in the pathogenesis of IR in obesity. We investigated the mitochondrial biogenesis in visceral fat (VF) and subcutaneous fat (SF) in C57BL/6J mice fed a high-fat, high-sucrose diet for 12 months. Results Impairment of glucose tolerance and insulin sensitivity developed after one month of the diet and was associated with a prompt increase of VF. The VF adipocytes were larger than those in the SF and had increased expressions of HIF1? and p-NF?B p65. However, alteration of mitochondrial biogenesis did not occur in the early stage, when increased intracellular reactive oxygen species (ROS), mitochondrial oxygen consumption rate, and mitochondrial ROS emerged at the 1st, 2nd and 2nd month, respectively. Until the 6th month, the VF had markedly increased mitochondrial DNA content and expression of PGC1?, Tfam, ATP5A, and MnSOD. This increase of mitochondrial biogenesis was followed by a generalized decrease at the 12th month and the mitochondrial morphology altered markedly. In the late stage, although mitochondrial ROS decreased, the increased expression of 8-OHdG in VF continued. Innovation and Conclusion These data suggest that IR and ROS production occur before the biphasic changes of mitochondrial biogenesis in adipose tissue and the VF plays a more crucial role.
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MicroRNA-29a protects against acute liver injury in a mouse model of obstructive jaundice via inhibition of the extrinsic apoptosis pathway.
Apoptosis
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Recent studies have shown that microRNA-29 (miR-29) is significantly decreased in liver fibrosis, as demonstrated in human liver cirrhosis, and that its downregulation influences the activation of hepatic stellate cells. In addition, both cleaved caspase-3 production and apoptosis play a role in cholestatic liver injury. However, it is unknown if miR-29 is effective in modulating the extent of injury. We employed miR-29a transgenic mice (miR-29aTg mice) and wild-type (WT) littermates to clarify the role of miR-29 in hepatic injury and fibrogenesis, using the bile duct-ligation (BDL) mouse model. After BDL, all three members of the miR-29 family were significantly downregulated in the livers of WT mice, and miR-29b and miR-29c were significantly downregulated in the livers of the miR-29aTg mice. Liver function, as measured by alanine transaminase and aspartate transaminase activity, was significantly improved in the miR-29aTg mice than in the WT littermates, following 1 week of obstructive jaundice. In addition, overexpression of miR-29a was associated with a significant downregulation of the expression of collagen-1?1, collagen-4?1, phospho-FADD, cleaved caspase-8, cleaved caspase-3, Bax, Bcl-2, PARP, and nuclear factor-?B, as well as an upregulation of phospho-AKT expression. In addition, there were significantly fewer TUNEL-positive liver cells in the miR-29aTg group than in the WT littermates after BDL. Our results indicate that miR-29a decreases cholestatic liver injury and fibrosis after BDL, at least partially, by modulating the extrinsic rather than intrinsic pathway of apoptosis.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.