A Critical Review of the Durability of Adhesion to Tooth Tissue: Methods and Results

2005 ◽  
Vol 84 (2) ◽  
pp. 118-132 ◽  
Author(s):  
J. De Munck ◽  
K. Van Landuyt ◽  
M. Peumans ◽  
A. Poitevin ◽  
P. Lambrechts ◽  
...  
Keyword(s):  
Gold Standard ◽  
Test Method ◽  
Chemical Degradation ◽  
Morphological Evidence ◽  
Aging Effects ◽  
Application Procedure ◽  
Etch And Rinse ◽  
Clinical Benefits

The immediate bonding effectiveness of contemporary adhesives is quite favorable, regardless of the approach used. In the long term, the bonding effectiveness of some adhesives drops dramatically, whereas the bond strengths of other adhesives are more stable. This review examines the fundamental processes that cause the adhesion of biomaterials to enamel and dentin to degrade with time. Non-carious class V clinical trials remain the ultimate test method for the assessment of bonding effectiveness, but in addition to being high-cost, they are time- and labor-consuming, and they provide little information on the true cause of clinical failure. Therefore, several laboratory protocols were developed to predict bond durability. This paper critically appraises methodologies that focus on chemical degradation patterns of hydrolysis and elution of interface components, as well as mechanically oriented test set-ups, such as fatigue and fracture toughness measurements. A correlation of in vitro and in vivo data revealed that, currently, the most validated method to assess adhesion durability involves aging of micro-specimens of biomaterials bonded to either enamel or dentin. After about 3 months, all classes of adhesives exhibited mechanical and morphological evidence of degradation that resembles in vivo aging effects. A comparison of contemporary adhesives revealed that the three-step etch-and-rinse adhesives remain the ‘gold standard’ in terms of durability. Any kind of simplification in the clinical application procedure results in loss of bonding effectiveness. Only the two-step self-etch adhesives approach the gold standard and do have some additional clinical benefits.

scholarly journals Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2545
Author(s):  
Ya-Hui Chen ◽  
Po-Hui Wang ◽  
Pei-Ni Chen ◽  
Shun-Fa Yang ◽  
Yi-Hsuan Hsiao
Keyword(s):  
Cervical Cancer ◽  
Potential Role ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
Anticancer Effects ◽  
Clinical Benefits ◽  
Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

scholarly journals Apoptosis in metanephric development.

1992 ◽  
Vol 119 (5) ◽  
pp. 1327-1333 ◽  
Author(s):  
C Koseki ◽  
D Herzlinger ◽  
Q al-Awqati
Keyword(s):  
Spinal Cord ◽  
Protein Kinase ◽  
Transcriptional Activation ◽  
Phorbol Esters ◽  
Dna Degradation ◽  
Morphological Evidence ◽  
Metanephric Mesenchyme ◽  
Embryonic Spinal Cord

During metanephric development, non-polarized mesenchymal cells are induced to form the epithelial structures of the nephron following interaction with extracellular matrix proteins and factors produced by the inducing tissue, ureteric bud. This induction can occur in a transfilter organ culture system where it can also be produced by heterologous cells such as the embryonic spinal cord. We found that when embryonic mesenchyme was induced in vitro and in vivo, many of the cells surrounding the new epithelium showed morphological evidence of programmed cell death (apoptosis) such as condensed nuclei, fragmented cytoplasm, and cell shrinking. A biochemical correlate of apoptosis is the transcriptional activation of a calcium-sensitive endonuclease. Indeed, DNA isolated from uninduced mesenchyme showed progressive degradation, a process that was prevented by treatment with actinomycin-D or cycloheximide and by buffering intracellular calcium. These results demonstrate that the metanephric mesenchyme is programmed for apoptosis. Incubation of mesenchyme with a heterologous inducer, embryonic spinal cord prevented this DNA degradation. To investigate the mechanism by which inducers prevented apoptosis we tested the effects of protein kinase C modulators on this process. Phorbol esters mimicked the effects of the inducer and staurosporine, an inhibitor of this protein kinase, prevented the effect of the inducer. EGF also prevented DNA degradation but did not lead to differentiation. These results demonstrate that conversion of mesenchyme to epithelial requires at least two steps, rescue of the mesenchyme from apoptosis and induction of differentiation.

scholarly journals Skrining Mekanisme Kerja Daun Malaka (Phyllanthus emblica L.) Sebagai Antidiabetes

2018 ◽  
Vol 1 (3) ◽  
pp. 106-110
Author(s):  
Novi Irwan Fauzi ◽  
Seno Aulia Ardiansyah ◽  
Saeful Hidayat
Keyword(s):  
Mechanism Of Action ◽  
Inhibitory Activity ◽  
Leaf Extract ◽  
Test Method ◽  
Diabetic Rat ◽  
Phyllanthus Emblica ◽  
Insulin Sensitizer ◽  
Water Fraction

Daun malaka (Phyllanthus emblica L.) mempunyai potensi digunakan sebagai alternatif obat antidiabetes. Daun malaka menunjukkan efek hipoglikemia pada tikus yang diinduksi aloksan. Namun, mekanisme kerjanya belum diketahui pasti. Penelitian ini dilakukan dalam rangka skrining mekanisme kerja daun malaka sebagai antidiabetes. Skrining mekanisme kerja dilakukan terhadap fraksi air daun malaka melalui uji aktivitas inhibisi enzim α-glukosidase serta α-amilase secara in vitro dan pengujian aktivitas insulin-sensitizer terhadap ekstrak daun malaka dengan metode tes toleransi insulin secara in vivo. Fraksi air daun malaka menunjukkan aktivitas inhibisi terhadap enzim α-glukosidase serta α-amilase dengan nilai IC50 (Inhibitor Concentration 50) pada kedua enzim tersebut berturut-turut adalah 0,87% dan 8,64% b/v. Pada uji aktivitas insulin sensitizer, pemberian ekstrak daun malaka dapat meningkatkan sensitivitas insulin pada tikus diabet dengan kondisi resistensi insulin. Nilai KTTI pada kelompok tikus diabet yang diberi ekstrak daun malaka dosis 100 dan 500 mg/kgbb tikus (74,89 dan 75,57) lebih tinggi dibandingkan kelompok tikus diabet (38,41) dan kadar glukosa darah yang lebih rendah selama interval waktu pengukuran. Daun malaka telah diketahui mampu meningkatkan sekresi insulin dan pada penelitian ini menunjukkan aktivitas inhibisi enzim α-glukosidase serta α-amilase secara in vitro dan menunjukkan aktivitas insulinsensitizer pada tikus diabet dengan kondisi resistensi insulin.   Malaka leaf (Phyllanthus emblica L.) has the potential to be used as an alternative antidiabetic drug. Malacca leaves showed hypoglycemia effect in rat induced by alloxan. However, the mechanism of action is not yet known. This study was conducted to evaluate the mechanism of action of Malaka leaves as antidiabetic. Screening of the mechanism of action was carried out on the water fraction of Malaka leaf  byinhibitory activity examination  on α-glucosidase and α-amylase by in vitro studyand Evaluation of insulin-sensitizer activity of Maaka leaf leaf extract was conducted by invivo  insulin tolerance test method. Malaka leaf water fraction showed inhibitory activity against the α-glucosidase and α-amylase with IC50 values ​​(Inhibitory Concentration 50)  of0.87% and 8.64% b / v on both enzyme, respectively. The evaluation of insulin sensitizer revelead that administration ofMalaka  leaf extract can increase insulin sensitivity in diabetic rat with insulin resistance.KTTI values ​​in diabetic rats given malaka extract  at the dose of 100 and 500 mg / kg BW (74.89 and 75.57) were higher than diabetics rat (38.41) and the extract also decrease blood glucose levels during measurement time intervals . Malaka leafhas been known to increase insulin secretion and the study showedthe  inhibitory activity on α-glucosidase and α-amylase by in vitro study and showed insulinsensitizer activity in diabetic rat with insulin resistance.

scholarly journals Anatomic and Biochemical Correlates of the Dopamine Transporter Ligand 11C-PE2I in Normal and Parkinsonian Primates: Comparison with 6-[18F]Fluoro-L-Dopa

2001 ◽  
Vol 21 (7) ◽  
pp. 782-792 ◽  
Author(s):  
Thomas Poyot ◽  
Françoise Condé ◽  
Marie-Claude Grégoire ◽  
Vincent Frouin ◽  
Christine Coulon ◽  
...  
Keyword(s):  
Gold Standard ◽  
Dopaminergic Neurons ◽  
Emission Tomography ◽  
Attractive Alternative ◽  
Input Rate ◽  
Nigrostriatal Pathway ◽  
Positron Emission ◽  
Neuroprotective Strategies

Positron emission tomography (PET) coupled to 6-[18F]Fluoro-L-Dopa (18F-Dopa) remains the gold standard for assessing dysfunctionality concerning the dopaminergic nigrostriatal pathway in Parkinson's disease and related disorders. The use of ligands of the dopamine transporters (DAT) is an attractive alternative target; consequently, the current aim was to validate one of them, 11C-PE2I, using a multiinjection modeling approach allowing accurate quantitation of DAT densities in the striatum. Experiments were performed in three controls, three MPTP-treated (parkinsonian) baboons, and one reserpine-treated baboon. 11C-PE2I B′max values obtained with this approach were compared with 18F-Dopa input rate constant values (Ki), in vitro Bmax binding of 125I-PE2I, and the number of dopaminergic neurons in the substantia nigra estimated postmortem by stereology. In the caudate nucleus and putamen, control values for 11C-PE2I B'max were 673 and 658 pmol/mL, respectively, whereas it was strongly reduced in the MPTP-treated (B′max = 26 and 36 pmol/mL) and reserpine-treated animals (B′max = 338 and 483 pmol/mL). In vivo11C-PE2I B′max values correlated with 18F-Dopa Ki values and in vitro125I-PE2I Bmax values in the striatum and with the number of nigral dopaminergic neurons. Altogether, these data support the use of 11C-PE2I for monitoring striatal dopaminergic disorders and the effect of potential neuroprotective strategies.

Abstract MP165: Exosome-mediated Encapsulation Alters AAV Antigenicity and Infectivity: Implications for Gene Delivery in the Heart

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Marta Adamiak ◽  
Yaxuan Liang ◽  
Cherrie Sherman ◽  
Shweta Lodha ◽  
Erik Kohlbrenner ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Cardiac Function ◽  
Neutralizing Antibodies ◽  
Firefly Luciferase ◽  
Interferometric Imaging ◽  
Human Cardiomyocytes ◽  
Clinical Benefits

Gene therapy is a promising approach for the treatment of cardiovascular disease. Current strategies for myocardial gene transfer include the use of adeno-associated virus (AAV) vectors. However, AAVs may not be ideal for gene therapy vectors owing to pre-existing AAV capsid immunity in the human population that may reduce transduction efficacy and hinder preclinical-to-clinical translation. Interestingly, recent studies suggest that exosome-mediated encapsulation may protect viruses from neutralizing antibodies (NAbs) against the capsid and promote viral infectivity. Here, we describe the ability of exosome-enveloped AAVs, i.e. exosomal AAVs (eAAVs), to evade NAbs and serve as a highly efficient gene delivery tool for cardiovascular therapeutics. We have developed a method to purifiy eAAVs from AAV-producing HEK-293T cells, and used electron/confocal microscopy, qPCR, immunoblotting, dynamic light scattering and interferometric imaging measurements to characterize eAAV morphology, contents and mechanism of action. We confirmed eAAVs represent vesicular fractions that exhibit common exosome phenotype, along with the presence of virus particles, and demonstrated that eAAV infectious entry potentially involves trafficking via endocytic compartments. Using flow cytometry, Langendorff perfusion system and bioluminescence imaging, we then evaluated efficiency of heart targeting for eAAV9/eAAV6 and standard AAV9/AAV6 encoding for mCherry or firefly luciferase in human cardiomyocytes in vitro and in mouse model in vivo . Regardless of the presence or absence of NAbs, we showed that eAAVs are more efficient in transduction in the same titer ranges as compared to standard AAVs. To test therapeutic efficacy, we intramyocardially injected eAAV9 or AAV9 vectors encoding for SERCA2a in NAb+ post-myocardial infarction mice and further evaluated cardiac function using echocardiography. Remarkably, eAAV9-SERCA2a outperformed standard AAVs significantly improving cardiac function in the presence of NAbs (%EF 55.14 ± 3.50 compared to 27.31 ± 1.63 at 6 weeks, respectively). In summary, delivery of AAVs protected by carrier exosomes (i.e. eAAVs) may retain the clinical benefits of AAVs while addressing one of its major challenges.

scholarly journals The application of resveratrol to mesenchymal stromal cell-based regenerative medicine

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Chenxia Hu ◽  
Lanjuan Li
Keyword(s):  
Regenerative Medicine ◽  
Tissue Injury ◽  
Lineage Commitment ◽  
Root Extract ◽  
Therapeutic Effects ◽  
Aging Effects ◽  
Chronic Injury ◽  
Self Renewal

Abstract Currently, the transplantation of mesenchymal stromal cells (MSCs) has emerged as an effective strategy to protect against tissue and organ injury. MSC transplantation also serves as a promising therapy for regenerative medicine, while poor engraftment and limited survival rates are major obstacles for its clinical application. Although multiple studies have focused on investigating chemicals to improve MSC stemness and differentiation in vitro and in vivo, there is still a shortage of effective and safe agents for MSC-based regenerative medicine. Resveratrol (RSV), a nonflavonoid polyphenol phytoalexin with a stilbene structure, was first identified in the root extract of white hellebore and is also found in the roots of Polygonum cuspidatum, and it is widely used in traditional Chinese medicine. RSV is a natural agent that possesses great therapeutic potential for protecting against acute or chronic injury in multiple tissues as a result of its antioxidative, anti-inflammatory, and anti-cancer properties. According to its demonstrated properties, RSV may improve the therapeutic effects of MSCs via enhancing their survival, self-renewal, lineage commitment, and anti-aging effects. In this review, we concluded that RSV significantly improved the preventive and therapeutic effects of MSCs against multiple diseases. We also described the underlying mechanisms of the effects of RSV on the survival, self-renewal, and lineage commitment of MSCs in vitro and in vivo. Upon further clarification of the potential mechanisms of the effects of RSV on MSC-based therapy, MSCs may be able to be more widely used in regenerative medicine to promote recovery from tissue injury.

scholarly journals The Foodborne Strain Lactobacillus fermentum MBC2 Triggers pept-1-Dependent Pro-Longevity Effects in Caenorhabditis elegans

2019 ◽  
Vol 7 (2) ◽  
pp. 45 ◽  
Author(s):  
Emily Schifano ◽  
Paola Zinno ◽  
Barbara Guantario ◽  
Marianna Roselli ◽  
Sante Marcoccia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Acid Tolerance ◽  
Lactobacillus Fermentum ◽  
In Vivo Model ◽  
Aging Effects ◽  
Pumping Rate ◽  
Gut Colonization

Lactic acid bacteria (LAB) are involved in several food fermentations and many of them provide strain-specific health benefits. Herein, the probiotic potential of the foodborne strain Lactobacillus fermentum MBC2 was investigated through in vitro and in vivo approaches. Caenorhabditis elegans was used as an in vivo model to analyze pro-longevity and anti-aging effects. L. fermentum MBC2 showed a high gut colonization capability compared to E. coli OP50 (OP50) or L. rhamnosus GG (LGG). Moreover, analysis of pumping rate, lipofuscin accumulation, and body bending showed anti-aging effects in L. fermentum MBC2-fed worms. Studies on PEPT-1 mutants demonstrated that pept-1 gene was involved in the anti-aging processes mediated by this bacterial strain through DAF-16, whereas the oxidative stress protection was PEPT-1 independent. Moreover, analysis of acid tolerance, bile tolerance, and antibiotic susceptibility were evaluated. L. fermentum MBC2 exerted beneficial effects on nematode lifespan, influencing energy metabolism and oxidative stress resistance, resulted in being tolerant to acidic pH and able to adhere to Caco-2 cells. Overall, these findings provide new insight for application of this strain in the food industry as a newly isolated functional starter. Furthermore, these results will also shed light on C. elegans molecular players involved in host-microbe interactions.

Effect of NVP-BEZ235, a dual PI3K/mTOR inhibitor, on chemotherapy and antiangiogenic response in pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 243-243 ◽  
Author(s):  
Katherine T. Ostapoff ◽  
Niranjan Awasthi ◽  
Peter L. Yen ◽  
Changhua Zhang ◽  
Margaret A. Schwarz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Mtor Inhibitor ◽  
Mammalian Target Of Rapamycin ◽  
Animal Experiments ◽  
Ductal Adenocarcinoma ◽  
Clinical Benefits ◽  
Induced Apoptosis

243 Background: The phosphatidylinositol-3-kinase (PI3K)/AKT and mammalian target of rapamycin (mTOR) signaling pathway dysregulation is a prominent feature of pancreatic ductal adenocarcinoma (PDAC). Gemcitabine (GEM), a standard systemic treatment for PDAC, has limited clinical benefits. The present study investigated the effects of NVP-BEZ235 (BEZ235), a novel dual PI3K/mTOR inhibitor, in combination with gemcitabine and endothelial monocyte activating polypeptide II (EMAP) in experimental PDAC. Methods: Protein expression and cell proliferation were analyzed by Western blotting and WST-1 assay. Animal experiments were performed in murine xenografts. Results: BEZ235 inhibited phospho-AKT (Ser473) and phospho-mTOR (Ser2448) expression in PDAC (AsPC-1), endothelial (HUVECs) and fibroblast (WI-38) cells. NVP-BEZ235 also caused a significant dephosphorylation of downstream mTORC1 target proteins phospho-p70 S6K (Thr389) and phospho-4E-BP1 (Thr37/46). In vitro 72-hour proliferation of four PDAC cell lines was significantly inhibited by BEZ235. Additive effects on proliferation inhibition were observed in the BEZ235 and GEM combination in PDAC cells and in combination of BEZ235 or EMAP with gemcitabine in HUVECs and WI-38 cells. BEZ235, alone or in combination with GEM and EMAP, induced apoptosis in AsPC-1, HUVECs and WI-38 cells as observed by increased expression of cleaved poly (ADP-ribose) polymerase-1 (PARP-1) and caspase-3 proteins. PDAC in vivo therapy demonstrated that compared to controls (median survival: 16 days), animal survival increased after BEZ235 and EMAP therapy alone (both 21 days) and GEM monotherapy (28 days). Further increases in survival occurred in combination therapy groups BEZ235+GEM (30 days, p=0.007), BEZ235+EMAP (27 days, p=0.02), GEM+EMAP (31 days, p=0.001) and BEZ235+GEM +EMAP (33 days, p=0.004). Conclusions: BEZ235 has experimental PDAC antitumor activity in vitro and in vivo that can be enhanced in combination with cytotoxic (GEM) and antiendothelial (EMAP) agents. These findings demonstrate advantages of combination therapy strategies targeting multiple pathways in pancreatic cancer treatment.

Sign in / Sign up

Export Citation Format

Share Document