Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the ...most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients.
LIBSVM Chang, Chih-Chung; Lin, Chih-Jen
ACM transactions on intelligent systems and technology,
04/2011, Volume:
2, Issue:
3
Journal Article
Peer reviewed
LIBSVM is a library for Support Vector Machines (SVMs). We have been actively developing this package since the year 2000. The goal is to help users to easily apply SVM to their applications. LIBSVM ...has gained wide popularity in machine learning and many other areas. In this article, we present all implementation details of LIBSVM. Issues such as solving SVM optimization problems theoretical convergence multiclass classification probability estimates and parameter selection are discussed in detail.
The aldolase family members involved in metabolism and glycolysis are present in three isoforms: ALDOA, ALDOB, and ALDOC. Aldolases are differentially expressed in human tissues, and aberrant ...expression has been observed in several human diseases and cancer types. However, non-enzymatic functions through protein–protein interactions or epigenetic modifications have been reported in recent years. Using high-throughput screening and -omics database integration, aldolase has been validated as an independent clinical prognostic marker of human cancers. Therefore, the aim of this review was to provide potential clinical value from in silico predictions and also summarize well-known signaling axes or phenotypes in various cancer types. Finally, we discuss the role of aldolase in the treatment of human diseases and cancers.
The enzymatic and non-enzymatic functions of glycolysis promote tumor cell growth, cell cycle, and cancer metastasis.
Isoforms of aldolases are abundant in the human body and play roles in glycolysis, fructolysis, and the synthesis of glyceraldehyde and ATP.
The expression of aldolase family members is associated with poor survival rates or multiple clinical parameters in several cancer types.
In silico analysis assesses the clinical value of aldolase family members as prognostic and diagnostic markers of human cancers and diseases.
The non-enzymatic functions of aldolases reveal novel phenotypes or signaling through protein–protein interactions.
Thermotolerance is a polygenic trait that contributes to cell survival and growth under unusually high temperatures. Although some genes associated with high-temperature growth (Htg+) have been ...identified, how cells accumulate mutations to achieve prolonged thermotolerance is still mysterious. Here, we conducted experimental evolution of a Saccharomyces cerevisiae laboratory strain with stepwise temperature increases for it to grow at 42 °C. Whole genome resequencing of 14 evolved strains and the parental strain revealed a total of 153 mutations in the evolved strains, including single nucleotide variants, small INDELs, and segmental duplication/deletion events. Some mutations persisted from an intermediate temperature to 42 °C, so they might be Htg+ mutations. Functional categorization of mutations revealed enrichment of exonic mutations in the SWI/SNF complex and F-type ATPase, pointing to their involvement in high-temperature tolerance. In addition, multiple mutations were found in a general stress-associated signal transduction network consisting of Hog1 mediated pathway, RAS-cAMP pathway, and Rho1-Pkc1 mediated cell wall integrity pathway, implying that cells can achieve Htg+ partly through modifying existing stress regulatory mechanisms. Using pooled segregant analysis of five Htg+ phenotype-orientated pools, we inferred causative mutations for growth at 42 °C and identified those mutations with stronger impacts on the phenotype. Finally, we experimentally validated a number of the candidate Htg+ mutations. This study increased our understanding of the genetic basis of yeast tolerance to high temperature.
Background:
Skeletal muscle injuries are very common in sports medicine. Conventional therapies have limited clinical efficacy. New treatment methods should be developed to allow athletes to return ...to play with better function.
Purpose:
To evaluate the in vitro differentiation potential of bone marrow–derived mesenchymal stem cells and the in vivo histologic and physiologic effects of mesenchymal stem cell therapy on muscle healing after contusion injury.
Study Design:
Controlled laboratory study.
Methods:
Bone marrow cells were flushed from both femurs of 5-week-old C57BL/6 mice to establish immortalized mesenchymal stem cell lines. A total of 36 mice aged 8 to 10 weeks were used to develop a muscle contusion model and were divided into 6 groups (6 mice/group) on the basis of the different dosages of IM2 cells to be injected (0, 1.25 × 105, and 2.5 × 105 cells with/without F-127 in 100 μL of phosphate-buffered saline). Histological analysis of muscle regeneration was performed, and the fast-twitch and tetanus strength of the muscle contractions was measured 28 days after muscle contusion injury, after injections of different doses of mesenchymal stem cells with or without the F-127 scaffold beginning 14 days after contusion injury.
Results:
The mesenchymal stem cell–treated muscles exhibited numerous regenerating myofibers. All the groups treated with mesenchymal stem cells (1.25 × 105 cells, 2.5 × 105 cells, 1.25 × 105 cells plus F-127, and 2.5 × 105 cells plus F-127) exhibited a significantly higher number of regenerating myofibers (mean ± SD: 111.6 ± 14.77, 133.4 ± 21.44, 221.89 ± 32.65, and 241.5 ± 25.95, respectively) as compared with the control group and the control with F-127 (69 ± 18.79 and 63.2 ± 18.98). The physiologic evaluation of fast-twitch and tetanus strength did not reveal differences between the age-matched uninjured group and the groups treated with various doses of mesenchymal stem cells 28 days after contusion. Significant differences were found between the control group and the groups treated with various doses of mesenchymal stem cells after muscle contusion.
Conclusion:
Mesenchymal stem cell therapy increased the number of regenerating myofibers and improved fast-twitch and tetanus muscle strength in a mouse model of muscle contusion. However, the rapid decay of transplanted mesenchymal stem cells suggests a paracrine effect of this action. Treatment with mesenchymal stem cells at various doses combined with the F-127 scaffold is a potential therapy for a muscle contusion.
Clinical Relevance:
Mesenchymal stem cell therapy has an effect on sports medicine because of its effects on myofiber regeneration and muscle strength after contusion injury.
Fatty infiltration of the pancreas has been shown to interfere with insulin secretion. Both insulin sensitivity and secretion are important in the pathogenesis of diabetes and prediabetes. However, ...the relationship between diabetes, prediabetes, and fatty pancreas remains unknown. We aim to investigate the relationships that fatty pancreas and nonalcoholic fatty liver disease (NAFLD) have with prediabetes and diabetes in a Chinese population.
This was a cross-sectional study. A total of 7,464 subjects were recruited. NAFLD and fatty pancreas were assessed by sonography. Clinico-metabolic parameters were compared among subjects with normoglycemia, prediabetes, and diabetes. Multinomial logistic regression was used to evaluate the relationship between fatty pancreas and NAFLD and diabetes or prediabetes with adjustment for cardiometabolic risk factors.
With an increase in glycemia, a significantly greater proportion of subjects had NAFLD and fatty pancreas (test for trend p<0.05). Similar trends were also found for hypertension, general and central obesity, low-HDL cholesterol, and hypertriglyceridemia. In the logistic regression analysis, age, hypertension, male gender, hypertriglyceridemia, and central obesity were significantly associated with prediabetes and diabetes. Furthermore, the ORs of prediabetes and diabetes for NAFLD were 1.798 (95% CI 1.544-2.094) and 2.578 (95% CI 2.024-3.284), respectively. In addition, fatty pancreas was independently related to diabetes (OR, 1.379; 95% CI, 1.047-1.816) and prediabetes (OR, 1.222; 95% CI, 1.002-1.491) in male subjects.
Both NAFLD and fatty pancreas were associated with diabetes independent of age, gender, adiposity, and other cardiometabolic risk factors. Fatty pancreas was also related to prediabetes in males.
Parallel Spectral Clustering in Distributed Systems Chen, Wen-Yen; Song, Yangqiu; Bai, Hongjie ...
IEEE transactions on pattern analysis and machine intelligence,
03/2011, Volume:
33, Issue:
3
Journal Article
Peer reviewed
Spectral clustering algorithms have been shown to be more effective in finding clusters than some traditional algorithms, such as k-means. However, spectral clustering suffers from a scalability ...problem in both memory use and computational time when the size of a data set is large. To perform clustering on large data sets, we investigate two representative ways of approximating the dense similarity matrix. We compare one approach by sparsifying the matrix with another by the Nyström method. We then pick the strategy of sparsifying the matrix via retaining nearest neighbors and investigate its parallelization. We parallelize both memory use and computation on distributed computers. Through an empirical study on a document data set of 193,844 instances and a photo data set of 2,121,863, we show that our parallel algorithm can effectively handle large problems.
Cancer metabolic reprogramming promotes tumorigenesis and metastasis; however, the underlying molecular mechanisms are still being uncovered. In this study, we show that the glycolytic enzyme ...aldolase A (ALDOA) is a key enzyme involved in lung cancer metabolic reprogramming and metastasis. Overexpression of ALDOA increased migration and invasion of lung cancer cell lines
and formation of metastatic lung cancer foci
. ALDOA promoted metastasis independent of its enzymatic activity. Immunoprecipitation and proteomic analyses revealed γ-actin binds to ALDOA; blocking this interaction using specific peptides decreased metastasis both
and
. Screening of clinically available drugs based on the crystal structure of ALDOA identified raltegravir, an antiretroviral agent that targets HIV integrase, as a pharmacologic inhibitor of ALDOA-γ-actin binding that produced antimetastatic and survival benefits in a xenograft model with no significant toxicity. In summary, ALDOA promotes lung cancer metastasis by interacting with γ-actin. Targeting this interaction provides a new therapeutic strategy to treat lung cancer metastasis. SIGNIFICANCE: This study demonstrates the role of aldolase A and its interaction with γ-actin in the metastasis of non-small lung cancer and that blocking this interaction could be an effective cancer treatment.
Maintaining internal osmolality constancy is essential for life. Release of arginine vasopressin (AVP) in response to hyperosmolality is critical. Current hypotheses for osmolality sensors in ...circumventricular organs (CVOs) of the brain focus on mechanosensitive membrane proteins. The present study demonstrated that intracellular protein kinase WNK1 was involved. Focusing on vascular-organ-of-lamina-terminalis (OVLT) nuclei, we showed that WNK1 kinase was activated by water restriction. Neuron-specific conditional KO (cKO) of Wnk1 caused polyuria with decreased urine osmolality that persisted in water restriction and blunted water restriction-induced AVP release. Wnk1 cKO also blunted mannitol-induced AVP release but had no effect on osmotic thirst response. The role of WNK1 in the osmosensory neurons in CVOs was supported by neuronal pathway tracing. Hyperosmolality-induced increases in action potential firing in OVLT neurons was blunted by Wnk1 deletion or pharmacological WNK inhibitors. Knockdown of Kv3.1 channel in OVLT by shRNA reproduced the phenotypes. Thus, WNK1 in osmosensory neurons in CVOs detects extracellular hypertonicity and mediates the increase in AVP release by activating Kv3.1 and increasing action potential firing from osmosensory neurons.
The purpose of this article is to propose a splitting algorithm for finding a common zero of a finite family of inclusion problems of accretive operators in Banach space. Under suitable conditions, ...some strong convergence theorems of the sequence generalized by the algorithm to a common zero of the inclusion problems are proved. Some applications to the convex minimization problem, common fixed point problem of a finite family of pseudocontractive mappings, and accretive variational inequality problem in Banach spaces are presented.
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