Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2016.04.001
Faruk Tas, Elif Bilgin, Senem Karabulut, Kayhan Erturk, Derya Duranyildiz
Background
Protease-Activated Receptor-1 (PAR-1) plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of PAR-1in cutaneous melanoma patients.
Methods
A total of 60 patients with a pathologically confirmed diagnosis of cutaneous melanoma were enrolled into this study. Serum PAR-1concentrations were determined by the solid-phase sandwich ELISA method.
Results
No significant difference in serum PAR-1 levels between melanoma patients and healthy controls was found (p = 0.07). The known clinical variables including age of patient, gender, site of lesion, histology, stage of disease, serum LDH levels and chemotherapy responsiveness were not correlated with serum PAR-1 concentrations (p > 0.05). Likewise, serum PAR-1 concentration had also no prognostic role on survival (p = 0.41).
Conclusion
Serum levels of PAR-1 have no diagnostic, predictive and prognostic roles in cutaneous melanoma patients.
General significance
Measurement of PAR-1 in serum is not a clinical significance in cutaneous melanoma patients.
{"title":"Clinical significance of serum Protease-Activated Receptor-1 (PAR-1) levels in patients with cutaneous melanoma","authors":"Faruk Tas, Elif Bilgin, Senem Karabulut, Kayhan Erturk, Derya Duranyildiz","doi":"10.1016/j.bbacli.2016.04.001","DOIUrl":"10.1016/j.bbacli.2016.04.001","url":null,"abstract":"<div><h3>Background</h3><p>Protease-Activated Receptor-1 (PAR-1) plays an important role in the pathogenesis of multiple malignancies and its expression strongly also affects the outcomes of cancer patients. The objective of this study was to determine the clinical significance of the serum levels of PAR-1in cutaneous melanoma patients.</p></div><div><h3>Methods</h3><p>A total of 60 patients with a pathologically confirmed diagnosis of cutaneous melanoma were enrolled into this study. Serum PAR-1concentrations were determined by the solid-phase sandwich ELISA method.</p></div><div><h3>Results</h3><p>No significant difference in serum PAR-1 levels between melanoma patients and healthy controls was found (p<!--> <!-->=<!--> <!-->0.07). The known clinical variables including age of patient, gender, site of lesion, histology, stage of disease, serum LDH levels and chemotherapy responsiveness were not correlated with serum PAR-1 concentrations (p<!--> <!-->><!--> <!-->0.05). Likewise, serum PAR-1 concentration had also no prognostic role on survival (p<!--> <!-->=<!--> <!-->0.41).</p></div><div><h3>Conclusion</h3><p>Serum levels of PAR-1 have no diagnostic, predictive and prognostic roles in cutaneous melanoma patients.</p></div><div><h3>General significance</h3><p>Measurement of PAR-1 in serum is not a clinical significance in cutaneous melanoma patients.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.04.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34450911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2015.11.002
Abdo Jurjus , Assad Eid , Sahar Al Kattar , Marie Noel Zeenny , Alice Gerges-Geagea , Hanine Haydar , Anis Hilal , Doreid Oueidat , Michel Matar , Jihane Tawilah , Inaya Hajj Hussein , Pierre Schembri-Wismayer , Francesco Cappello , Giovanni Tomasello , Angelo Leone , Rosalyn A. Jurjus
The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFβ, NFKB, TNFα and ROS among others.
This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases.
The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array of pro-inflammatory mediators and other related biomolecules are up-regulated, both locally and systematically. Such a persistent or an inadequately resolved chronic inflammation may be a causative agent, in the presence other factors, leading to several pathologies such as IBD, CRC and T2DM.
TGFβ plays a crucial role in pancreatic β cell malfunctioning as glucotoxicity stimulates its signaling cascade through smad 3, IL-6 and epithelial to mesenchymal transition. Such a cascade could lead to macrophages and other cells recruitment, inflammation, then IBD and CRC.
NFkB is also another key regulator in the crosstalk among the pathways leading to the three disease entities. It plays a major role in linking inflammation to cancer development through its ability to up regulate several inflammatory and tumor promoting cytokines like: IL-6, IL-1 α and TNF α, as well as genes like BCL2 and BCLXL. It activates JAK/STAT signaling network via STAT3 transcription factors and promotes epithelial to mesenchymal transition. It also increases the risk for T2DM in obese people. In brief, NFKB is a matchmaker between inflammation, IBD, cancer and diabetes.
In addition, TNFα plays a pivotal role in systemic inflammation. It is increased in the mucosa of IBD patients and has a central role in its pathogenesis. It also activates other signaling pathways like NFKB and MAPK leading to CRC. It is also overexpressed in the adipose tissues of obese patients thus linking it to T2DM, chronic inflammation and consequently CRC.
On the other hand, increasing evidence suggests that dysbiosis plays a role in initiating, maintaining and determining the severity of IBD. Actually, among its functions, it modulates genotoxic metabolites which are able to induce CRC, a fact proven to be sustained by stool transfer from patients with CRC. Probiotics, however, may actively prevent CRC as well as IBD and results in a significant decrease in fasting glycemia in T2DM patients.
In conclusion, IBD, CRC and T2DM are commonly occurring interrelated clinical problems. They share a common basis influenced by an inflammatory process, an imbalance in intestinal microbiota, and a crosstalk between various signaling pathways. Would probiotics interrupt the crosstalk or orient it in the
{"title":"Inflammatory bowel disease, colorectal cancer and type 2 diabetes mellitus: The links","authors":"Abdo Jurjus , Assad Eid , Sahar Al Kattar , Marie Noel Zeenny , Alice Gerges-Geagea , Hanine Haydar , Anis Hilal , Doreid Oueidat , Michel Matar , Jihane Tawilah , Inaya Hajj Hussein , Pierre Schembri-Wismayer , Francesco Cappello , Giovanni Tomasello , Angelo Leone , Rosalyn A. Jurjus","doi":"10.1016/j.bbacli.2015.11.002","DOIUrl":"10.1016/j.bbacli.2015.11.002","url":null,"abstract":"<div><p>The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFβ, NFKB, TNFα and ROS among others.</p><p>This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases.</p><p>The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array of pro-inflammatory mediators and other related biomolecules are up-regulated, both locally and systematically. Such a persistent or an inadequately resolved chronic inflammation may be a causative agent, in the presence other factors, leading to several pathologies such as IBD, CRC and T2DM.</p><p>TGFβ plays a crucial role in pancreatic β cell malfunctioning as glucotoxicity stimulates its signaling cascade through smad 3, IL-6 and epithelial to mesenchymal transition. Such a cascade could lead to macrophages and other cells recruitment, inflammation, then IBD and CRC.</p><p>NFkB is also another key regulator in the crosstalk among the pathways leading to the three disease entities. It plays a major role in linking inflammation to cancer development through its ability to up regulate several inflammatory and tumor promoting cytokines like: IL-6, IL-1 α and TNF α, as well as genes like BCL2 and BCLXL. It activates JAK/STAT signaling network via STAT3 transcription factors and promotes epithelial to mesenchymal transition. It also increases the risk for T2DM in obese people. In brief, NFKB is a matchmaker between inflammation, IBD, cancer and diabetes.</p><p>In addition, TNFα plays a pivotal role in systemic inflammation. It is increased in the mucosa of IBD patients and has a central role in its pathogenesis. It also activates other signaling pathways like NFKB and MAPK leading to CRC. It is also overexpressed in the adipose tissues of obese patients thus linking it to T2DM, chronic inflammation and consequently CRC.</p><p>On the other hand, increasing evidence suggests that dysbiosis plays a role in initiating, maintaining and determining the severity of IBD. Actually, among its functions, it modulates genotoxic metabolites which are able to induce CRC, a fact proven to be sustained by stool transfer from patients with CRC. Probiotics, however, may actively prevent CRC as well as IBD and results in a significant decrease in fasting glycemia in T2DM patients.</p><p>In conclusion, IBD, CRC and T2DM are commonly occurring interrelated clinical problems. They share a common basis influenced by an inflammatory process, an imbalance in intestinal microbiota, and a crosstalk between various signaling pathways. Would probiotics interrupt the crosstalk or orient it in the","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.11.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54180355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2016.03.002
Tae Woo Jung, Hye Jin Yoo, Kyung Mook Choi
The liver is a central regulator of systemic energy homeostasis and has a pivotal role in glucose and lipid metabolism. Impaired gluconeogenesis and dyslipidemia are often observed in patients with nonalcoholic fatty liver disease (NAFLD). The liver is now recognized to be an endocrine organ that secretes hepatokines, which are proteins that regulate systemic metabolism and energy homeostasis. Hepatokines are known to contribute to the pathogenesis of metabolic syndrome, NAFLD, type 2 diabetes (T2DM), and cardiovascular diseases (CVDs). In this review, we focus on the roles of two major hepatokines, fetuin-A and fibroblast growth factor 21 (FGF21), as well as recently-redefined hepatokines, such as selenoprotein P, angiopoietin-like protein 4 (ANGPTL4), and leukocyte cell-derived chemotaxin 2 (LECT2). We also assess the biology and molecular mechanisms of hepatokines in the context of their potential as therapeutic targets for metabolic disorders and cardiovascular diseases.
{"title":"Implication of hepatokines in metabolic disorders and cardiovascular diseases","authors":"Tae Woo Jung, Hye Jin Yoo, Kyung Mook Choi","doi":"10.1016/j.bbacli.2016.03.002","DOIUrl":"10.1016/j.bbacli.2016.03.002","url":null,"abstract":"<div><p>The liver is a central regulator of systemic energy homeostasis and has a pivotal role in glucose and lipid metabolism. Impaired gluconeogenesis and dyslipidemia are often observed in patients with nonalcoholic fatty liver disease (NAFLD). The liver is now recognized to be an endocrine organ that secretes hepatokines, which are proteins that regulate systemic metabolism and energy homeostasis. Hepatokines are known to contribute to the pathogenesis of metabolic syndrome, NAFLD, type 2 diabetes (T2DM), and cardiovascular diseases (CVDs). In this review, we focus on the roles of two major hepatokines, fetuin-A and fibroblast growth factor 21 (FGF21), as well as recently-redefined hepatokines, such as selenoprotein P, angiopoietin-like protein 4 (ANGPTL4), and leukocyte cell-derived chemotaxin 2 (LECT2). We also assess the biology and molecular mechanisms of hepatokines in the context of their potential as therapeutic targets for metabolic disorders and cardiovascular diseases.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.03.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2015.11.003
Cian O. Malley, Graham P. Pidgeon
The mechanistic target of rapamycin (mTOR) is a crucial point of convergence between growth factor signalling, metabolism, nutrient status and cellular proliferation. The mTOR pathway is heavily implicated in the progression of many cancers and is emerging as an important driver of gastrointestinal (GI) malignancies. Due to its central role in adapting metabolism to environmental conditions, mTOR signalling is also believed to be critical in the development of obesity. Recent research has delineated that excessive nutrient intake can promote signalling through the mTOR pathway and possibly evoke changes to cellular metabolism that could accelerate obesity related cancers. Acting through its two effector complexes mTORC1 and mTORC2, mTOR dictates the transcription of genes important in glycolysis, lipogenesis, protein translation and synthesis and has recently been defined as a central mediator of the Warburg effect in cancer cells. Activation of the mTOR pathway is involved in both the pathogenesis of GI malignancies and development of resistance to conventional chemotherapy and radiotherapy. The use of mTOR inhibitors is a promising therapeutic option in many GI malignancies, with greatest clinical efficacy seen in combination regimens. Recent research has also provided insight into crosstalk between mTOR and other pathways which could potentially expand the list of therapeutic targets in the mTOR pathway. Here we review the available strategies for targeting the mTOR pathway in GI cancers. We discuss current clinical trials of both established and novel mTOR inhibitors, with particular focus on combinations of these drugs with conventional chemotherapy, radiotherapy and targeted therapies.
{"title":"The mTOR pathway in obesity driven gastrointestinal cancers: Potential targets and clinical trials","authors":"Cian O. Malley, Graham P. Pidgeon","doi":"10.1016/j.bbacli.2015.11.003","DOIUrl":"10.1016/j.bbacli.2015.11.003","url":null,"abstract":"<div><p>The mechanistic target of rapamycin (mTOR) is a crucial point of convergence between growth factor signalling, metabolism, nutrient status and cellular proliferation. The mTOR pathway is heavily implicated in the progression of many cancers and is emerging as an important driver of gastrointestinal (GI) malignancies. Due to its central role in adapting metabolism to environmental conditions, mTOR signalling is also believed to be critical in the development of obesity. Recent research has delineated that excessive nutrient intake can promote signalling through the mTOR pathway and possibly evoke changes to cellular metabolism that could accelerate obesity related cancers. Acting through its two effector complexes mTORC1 and mTORC2, mTOR dictates the transcription of genes important in glycolysis, lipogenesis, protein translation and synthesis and has recently been defined as a central mediator of the Warburg effect in cancer cells. Activation of the mTOR pathway is involved in both the pathogenesis of GI malignancies and development of resistance to conventional chemotherapy and radiotherapy. The use of mTOR inhibitors is a promising therapeutic option in many GI malignancies, with greatest clinical efficacy seen in combination regimens. Recent research has also provided insight into crosstalk between mTOR and other pathways which could potentially expand the list of therapeutic targets in the mTOR pathway. Here we review the available strategies for targeting the mTOR pathway in GI cancers. We discuss current clinical trials of both established and novel mTOR inhibitors, with particular focus on combinations of these drugs with conventional chemotherapy, radiotherapy and targeted therapies.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.11.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54180474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2016.02.003
Brian K. McFarlin , Adam S. Venable , Andrea L. Henning , Jill N. Best Sampson , Kathryn Pennel , Jakob L. Vingren , David W. Hill
Background
Exercise-Induced Muscle Damage (EIMD) and delayed onset muscle soreness (DOMS) impact subsequent training sessions and activities of daily living (ADL) even in active individuals. In sedentary or diseased individuals, EIMD and DOMS may be even more pronounced and present even in the absence of structured exercise.
Methods
The purpose of this study was to determine the effects of oral curcumin supplementation (Longvida® 400 mg/days) on muscle & ADL soreness, creatine kinase (CK), and inflammatory cytokines (TNF-α, IL-6, IL-8, IL-10) following EMID (eccentric-only dual-leg press exercise). Subjects (N = 28) were randomly assigned to either curcumin (400 mg/day) or placebo (rice flour) and supplemented 2 days before to 4 days after EMID. Blood samples were collected prior to (PRE), and 1, 2, 3, and 4 days after EIMD to measure CK and inflammatory cytokines. Data were analyzed by ANOVA with P < 0.05.
Results
Curcumin supplementation resulted in significantly smaller increases in CK (− 48%), TNF-α (− 25%), and IL-8 (− 21%) following EIMD compared to placebo. We observed no significant differences in IL-6, IL-10, or quadriceps muscle soreness between conditions for this sample size.
Conclusions
Collectively, the findings demonstrated that consumption of curcumin reduced biological inflammation, but not quadriceps muscle soreness, during recovery after EIMD. The observed improvements in biological inflammation may translate to faster recovery and improved functional capacity during subsequent exercise sessions.
General significance
These findings support the use of oral curcumin supplementation to reduce the symptoms of EIMD. The next logical step is to evaluate further the efficacy of an inflammatory clinical disease model.
{"title":"Reduced inflammatory and muscle damage biomarkers following oral supplementation with bioavailable curcumin","authors":"Brian K. McFarlin , Adam S. Venable , Andrea L. Henning , Jill N. Best Sampson , Kathryn Pennel , Jakob L. Vingren , David W. Hill","doi":"10.1016/j.bbacli.2016.02.003","DOIUrl":"10.1016/j.bbacli.2016.02.003","url":null,"abstract":"<div><h3>Background</h3><p>Exercise-Induced Muscle Damage (EIMD) and delayed onset muscle soreness (DOMS) impact subsequent training sessions and activities of daily living (ADL) even in active individuals. In sedentary or diseased individuals, EIMD and DOMS may be even more pronounced and present even in the absence of structured exercise.</p></div><div><h3>Methods</h3><p>The purpose of this study was to determine the effects of oral curcumin supplementation (Longvida® 400<!--> <!-->mg/days) on muscle & ADL soreness, creatine kinase (CK), and inflammatory cytokines (TNF-α, IL-6, IL-8, IL-10) following EMID (eccentric-only dual-leg press exercise). Subjects (N<!--> <!-->=<!--> <!-->28) were randomly assigned to either curcumin (400<!--> <!-->mg/day) or placebo (rice flour) and supplemented 2<!--> <!-->days before to 4<!--> <!-->days after EMID. Blood samples were collected prior to (PRE), and 1, 2, 3, and 4<!--> <!-->days after EIMD to measure CK and inflammatory cytokines. Data were analyzed by ANOVA with P<!--> <!--><<!--> <!-->0.05.</p></div><div><h3>Results</h3><p>Curcumin supplementation resulted in significantly smaller increases in CK (−<!--> <!-->48%), TNF-α (−<!--> <!-->25%), and IL-8 (−<!--> <!-->21%) following EIMD compared to placebo. We observed no significant differences in IL-6, IL-10, or quadriceps muscle soreness between conditions for this sample size.</p></div><div><h3>Conclusions</h3><p>Collectively, the findings demonstrated that consumption of curcumin reduced biological inflammation, but not quadriceps muscle soreness, during recovery after EIMD. The observed improvements in biological inflammation may translate to faster recovery and improved functional capacity during subsequent exercise sessions.</p></div><div><h3>General significance</h3><p>These findings support the use of oral curcumin supplementation to reduce the symptoms of EIMD. The next logical step is to evaluate further the efficacy of an inflammatory clinical disease model.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.02.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2016.04.003
Sidika E. Karakas , Bertrand Perroud , Tobias Kind , Mine Palazoglu , Oliver Fiehn
Background
Both fish (FO) and flaxseed oils (FLX) are n-3 polyunsaturated fatty acids (PUFA). Fish oil contains long chain while FLX contains essential n-3 PUFA. We demonstrated that FO altered insulin secretion and resistance in polycystic ovary syndrome (PCOS) women but FLX did not. Surprisingly, the effects of FO were similar to those of the n-6 PUFA-rich soybean oil (SBO). Since increased branched chain (BCAA) and aromatic amino acids (AA) affect insulin secretion and resistance, we investigated whether FO, FLX and /or SBO affect plasma metabolites, especially AA.
Methods and findings
In this six-week, randomized, 3-parallel arm, double-blinded study, 54 women received 3.5 g/day FO, FLX or SBO. In 51 completers (17 from each arm), fasting plasma metabolites were measured at the beginning and at the end.
As compared to FLX, FO and SBO increased insulin response and resistance as well as several BCAA and aromatic AA. Pathway analysis indicated that FO exerted the largest biochemical impact, affecting AA degradation and biosynthesis, amine, polyamine degradation and alanine, glycine, l-carnitine biosynthesis and TCA cycle, while FLX had minimal impact affecting only alanine biosynthesis and l-cysteine degradation.
Conclusion
Effects of FO and SBO on plasma AA were similar and differed significantly from those of the FLX. The primary target of dietary PUFA is not known. Dietary PUFA may influence insulin secretion and resistance directly and alter plasma AA indirectly. Alternatively, as a novel concept, dietary PUFA may directly affect AA metabolism and the changes in insulin secretion and resistance may be secondary.
{"title":"Changes in plasma metabolites and glucose homeostasis during omega-3 polyunsaturated fatty acid supplementation in women with polycystic ovary syndrome","authors":"Sidika E. Karakas , Bertrand Perroud , Tobias Kind , Mine Palazoglu , Oliver Fiehn","doi":"10.1016/j.bbacli.2016.04.003","DOIUrl":"10.1016/j.bbacli.2016.04.003","url":null,"abstract":"<div><h3>Background</h3><p>Both fish (FO) and flaxseed oils (FLX) are n-3 polyunsaturated fatty acids (PUFA). Fish oil contains long chain while FLX contains essential n-3 PUFA. We demonstrated that FO altered insulin secretion and resistance in polycystic ovary syndrome (PCOS) women but FLX did not. Surprisingly, the effects of FO were similar to those of the n-6 PUFA-rich soybean oil (SBO). Since increased branched chain (BCAA) and aromatic amino acids (AA) affect insulin secretion and resistance, we investigated whether FO, FLX and /or SBO affect plasma metabolites, especially AA.</p></div><div><h3>Methods and findings</h3><p>In this six-week, randomized, 3-parallel arm, double-blinded study, 54 women received 3.5<!--> <!-->g/day FO, FLX or SBO. In 51 completers (17 from each arm), fasting plasma metabolites were measured at the beginning and at the end.</p><p>As compared to FLX, FO and SBO increased insulin response and resistance as well as several BCAA and aromatic AA. Pathway analysis indicated that FO exerted the largest biochemical impact, affecting AA degradation and biosynthesis, amine, polyamine degradation and alanine, glycine, <span>l</span>-carnitine biosynthesis and TCA cycle, while FLX had minimal impact affecting only alanine biosynthesis and <span>l</span>-cysteine degradation.</p></div><div><h3>Conclusion</h3><p>Effects of FO and SBO on plasma AA were similar and differed significantly from those of the FLX. The primary target of dietary PUFA is not known. Dietary PUFA may influence insulin secretion and resistance directly and alter plasma AA indirectly. Alternatively, as a novel concept, dietary PUFA may directly affect AA metabolism and the changes in insulin secretion and resistance may be secondary.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.04.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34550981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Magnetic resonance spectroscopy (MRS) is an established tool for in-vivo evaluation of the biochemical basis of human diseases. On one hand, such lucid depiction of ‘live biochemistry’ helps one to decipher the true nature of the pathology while on the other hand one can track the response to therapy at sub-cellular level. Brain tumors have been an area of continuous interrogation and instigation for mankind. Evaluation of these lesions by MRS plays a crucial role in the two aspects of disease management described above.
Scope of review
Presented is an overview of the window provided by MRS into the biochemical aspects of brain tumors. We systematically visit each metabolite deciphered by MRS and discuss the role of deconvoluting the biochemical aspects of pathologies (here in context of brain tumors) in the disease management cycle. We further try to unify a radiologist's perspective of disease with that of a biochemist to prove the point that preclinical work is the mother of the treatment we provide at bedside as clinicians. Furthermore, an integrated approach by various scientific experts help resolve a query encountered in everyday practice.
Major conclusions
MR spectroscopy is an integral tool for evaluation and systematic follow-up of brain tumors. A deeper understanding of this technology by a biochemist would help in a swift and more logical development of the technique while a close collaboration with radiologist would enable definitive application of the same.
General significance
The review aims at inciting closer ties between the two specialists enabling a deeper understanding of this valuable technology.
{"title":"Magnetic resonance spectroscopy — Revisiting the biochemical and molecular milieu of brain tumors","authors":"Ashish Verma , Ishan Kumar , Nimisha Verma , Priyanka Aggarwal , Ritu Ojha","doi":"10.1016/j.bbacli.2016.04.002","DOIUrl":"10.1016/j.bbacli.2016.04.002","url":null,"abstract":"<div><h3>Background</h3><p>Magnetic resonance spectroscopy (MRS) is an established tool for in-vivo evaluation of the biochemical basis of human diseases. On one hand, such lucid depiction of ‘live biochemistry’ helps one to decipher the true nature of the pathology while on the other hand one can track the response to therapy at sub-cellular level. Brain tumors have been an area of continuous interrogation and instigation for mankind. Evaluation of these lesions by MRS plays a crucial role in the two aspects of disease management described above.</p></div><div><h3>Scope of review</h3><p>Presented is an overview of the window provided by MRS into the biochemical aspects of brain tumors. We systematically visit each metabolite deciphered by MRS and discuss the role of deconvoluting the biochemical aspects of pathologies (here in context of brain tumors) in the disease management cycle. We further try to unify a radiologist's perspective of disease with that of a biochemist to prove the point that preclinical work is the mother of the treatment we provide at bedside as clinicians. Furthermore, an integrated approach by various scientific experts help resolve a query encountered in everyday practice.</p></div><div><h3>Major conclusions</h3><p>MR spectroscopy is an integral tool for evaluation and systematic follow-up of brain tumors. A deeper understanding of this technology by a biochemist would help in a swift and more logical development of the technique while a close collaboration with radiologist would enable definitive application of the same.</p></div><div><h3>General significance</h3><p>The review aims at inciting closer ties between the two specialists enabling a deeper understanding of this valuable technology.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.04.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34530731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2015.12.002
Eva Pardina , Roser Ferrer , Joana Rossell , Juan Antonio Baena-Fustegueras , Albert Lecube , Jose Manuel Fort , Enric Caubet , Óscar González , Ramón Vilallonga , Víctor Vargas , José María Balibrea , Julia Peinado-Onsurbe
Background & aims
To study the origin of fat excess in the livers of morbidly obese (MO) individuals, we analysed lipids and lipases in both plasma and liver and genes involved in lipid transport, or related with, in that organ.
Methods
Thirty-two MO patients were grouped according to the absence (healthy: DM − DL −) or presence of comorbidities (dyslipidemic: DM − DL +; or dyslipidemic with type 2 diabetes: DM + DL +) before and one year after gastric bypass.
Results
The livers of healthy, DL and DM patients contained more lipids (9.8, 9.5 and 13.7 times, respectively) than those of control subjects. The genes implicated in liver lipid uptake, including HL, LPL, VLDLr, and FAT/CD36, showed increased expression compared with the controls. The expression of genes involved in lipid-related processes outside of the liver, such as apoB, PPARα and PGC1α, CYP7a1 and HMGCR, was reduced in these patients compared with the controls. PAI1 and TNFα gene expression in the diabetic livers was increased compared with the other obese groups and control group. Increased steatosis and fibrosis were also noted in the MO individuals.
Conclusions
Hepatic lipid parameters in MO patients change based on their comorbidities. The gene expression and lipid levels after bariatric surgery were less prominent in the diabetic patients. Lipid receptor overexpression could enable the liver to capture circulating lipids, thus favouring the steatosis typically observed in diabetic and dyslipidaemic MO individuals.
{"title":"Diabetic and dyslipidaemic morbidly obese exhibit more liver alterations compared with healthy morbidly obese","authors":"Eva Pardina , Roser Ferrer , Joana Rossell , Juan Antonio Baena-Fustegueras , Albert Lecube , Jose Manuel Fort , Enric Caubet , Óscar González , Ramón Vilallonga , Víctor Vargas , José María Balibrea , Julia Peinado-Onsurbe","doi":"10.1016/j.bbacli.2015.12.002","DOIUrl":"10.1016/j.bbacli.2015.12.002","url":null,"abstract":"<div><h3>Background & aims</h3><p>To study the origin of fat excess in the livers of morbidly obese (MO) individuals, we analysed lipids and lipases in both plasma and liver and genes involved in lipid transport, or related with, in that organ.</p></div><div><h3>Methods</h3><p>Thirty-two MO patients were grouped according to the absence (healthy: DM<!--> <!-->−<!--> <!-->DL<!--> <!-->−) or presence of comorbidities (dyslipidemic: DM<!--> <!-->−<!--> <!-->DL<!--> <!-->+; or dyslipidemic with type 2 diabetes: DM<!--> <!-->+<!--> <!-->DL<!--> <!-->+) before and one year after gastric bypass.</p></div><div><h3>Results</h3><p>The livers of healthy, DL and DM patients contained more lipids (9.8, 9.5 and 13.7 times, respectively) than those of control subjects. The genes implicated in liver lipid uptake, including <em>HL</em>, <em>LPL</em>, <em>VLDLr</em>, and <em>FAT</em>/<em>CD36</em>, showed increased expression compared with the controls. The expression of genes involved in lipid-related processes outside of the liver, such as <em>apoB</em>, <em>PPARα</em> and <em>PGC1α</em>, <em>CYP7a1</em> and <em>HMGCR</em>, was reduced in these patients compared with the controls. <em>PAI1</em> and <em>TNFα</em> gene expression in the diabetic livers was increased compared with the other obese groups and control group. Increased steatosis and fibrosis were also noted in the MO individuals.</p></div><div><h3>Conclusions</h3><p>Hepatic lipid parameters in MO patients change based on their comorbidities. The gene expression and lipid levels after bariatric surgery were less prominent in the diabetic patients. Lipid receptor overexpression could enable the liver to capture circulating lipids, thus favouring the steatosis typically observed in diabetic and dyslipidaemic MO individuals.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2015.12.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2016.02.002
Rafael N. Moresco , Marijn M. Speeckaert , Slawomir C. Zmonarski , Magdalena Krajewska , Ewa Komuda-Leszek , Agnieszka Perkowska-Ptasinska , Loreto Gesualdo , Maria T. Rocchetti , Sigurd E. Delanghe , Raymond Vanholder , Wim Van Biesen , Joris R. Delanghe
Background
IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) are glomerular diseases that share a common and central pathogenic mechanism. The formation of immune complexes containing IgA1, myeloid IgA Fc alpha receptor (FcαRI/CD89) and transglutaminase-2 (TG2) is observed in both conditions. Therefore, urinary CD89 and TG2 could be potential biomarkers to identify active IgAN/HSPN.
Methods
In this multicenter study, 160 patients with IgAN or HSPN were enrolled. Urinary concentrations of CD89 and TG2, as well as some other biochemical parameters, were measured.
Results
Urinary CD89 and TG2 were lower in patients with active IgAN/HSPN compared to IgAN/HSPN patients in complete remission (P < 0.001). The CD89xTG2 formula had a high ability to discriminate active from inactive IgAN/HSPN in both situations: CD89xTG2/proteinuria ratio (AUC: 0.84, P < 0.001, sensitivity: 76%, specificity: 74%) and CD89xTG2/urinary creatinine ratio (AUC: 0.82, P < 0.001, sensitivity: 75%, specificity: 74%). Significant correlations between urinary CD89 and TG2 (r = 0.711, P < 0.001), proteinuria and urinary CD89 (r = − 0.585, P < 0.001), and proteinuria and urinary TG2 (r = − 0.620, P < 0.001) were observed.
Conclusions
Determination of CD89 and TG2 in urine samples can be useful to identify patients with active IgAN/HSPN.
diga肾病(IgAN)和Henoch-Schönlein紫癜性肾炎(HSPN)是具有共同中心致病机制的肾小球疾病。两种情况下均可观察到含有IgA1、髓系IgA Fcα受体(Fcα ri /CD89)和转谷氨酰胺酶-2 (TG2)的免疫复合物的形成。因此，尿CD89和TG2可能是鉴定活性IgAN/HSPN的潜在生物标志物。方法本研究纳入160例IgAN或HSPN患者。检测尿CD89、TG2浓度及其他生化指标。结果IgAN/HSPN活跃患者的CD89和TG2水平低于IgAN/HSPN完全缓解患者(P <0.001)。CD89xTG2配方在两种情况下都具有高度的区分活性和非活性IgAN/HSPN的能力:CD89xTG2/蛋白尿比(AUC: 0.84, P <0.001，敏感性:76%，特异性:74%)和CD89xTG2/尿肌酐比值(AUC: 0.82, P <0.001，敏感性:75%，特异性:74%)。尿CD89与TG2相关性显著(r = 0.711, P <0.001)、蛋白尿和尿CD89 (r = - 0.585, P <0.001)，蛋白尿和尿TG2 (r = - 0.620, P <0.001)。结论尿样中CD89和TG2的检测可用于IgAN/HSPN活动性的鉴别。
{"title":"Urinary myeloid IgA Fc alpha receptor (CD89) and transglutaminase-2 as new biomarkers for active IgA nephropathy and henoch-Schönlein purpura nephritis","authors":"Rafael N. Moresco , Marijn M. Speeckaert , Slawomir C. Zmonarski , Magdalena Krajewska , Ewa Komuda-Leszek , Agnieszka Perkowska-Ptasinska , Loreto Gesualdo , Maria T. Rocchetti , Sigurd E. Delanghe , Raymond Vanholder , Wim Van Biesen , Joris R. Delanghe","doi":"10.1016/j.bbacli.2016.02.002","DOIUrl":"10.1016/j.bbacli.2016.02.002","url":null,"abstract":"<div><h3>Background</h3><p>IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) are glomerular diseases that share a common and central pathogenic mechanism. The formation of immune complexes containing IgA1, myeloid IgA Fc alpha receptor (FcαRI/CD89) and transglutaminase-2 (TG2) is observed in both conditions. Therefore, urinary CD89 and TG2 could be potential biomarkers to identify active IgAN/HSPN.</p></div><div><h3>Methods</h3><p>In this multicenter study, 160 patients with IgAN or HSPN were enrolled. Urinary concentrations of CD89 and TG2, as well as some other biochemical parameters, were measured.</p></div><div><h3>Results</h3><p>Urinary CD89 and TG2 were lower in patients with active IgAN/HSPN compared to IgAN/HSPN patients in complete remission (<em>P</em> <!--><<!--> <!-->0.001). The CD89xTG2 formula had a high ability to discriminate active <strong>from inactive</strong> IgAN/HSPN in both situations<strong>: CD89xTG2/proteinuria ratio</strong> (AUC: 0.84, <em>P</em> <!--><<!--> <!-->0.001, sensitivity: 76%, specificity: 74%) <strong>and CD89xTG2/urinary creatinine ratio</strong> (AUC: 0.82, <em>P</em> <!--><<!--> <!-->0.001, sensitivity: 75%, specificity: 74%). Significant correlations between urinary CD89 and TG2 (r<!--> <!-->=<!--> <!-->0.711, <em>P</em> <!--><<!--> <!-->0.001), proteinuria and urinary CD89 (r<!--> <!-->=<!--> <!-->−<!--> <!-->0.585, <em>P</em> <!--><<!--> <!-->0.001), and proteinuria and urinary TG2 (r<!--> <!-->=<!--> <!-->−<!--> <!-->0.620, <em>P</em> <!--><<!--> <!-->0.001) were observed.</p></div><div><h3>Conclusions</h3><p>Determination of CD89 and TG2 in urine samples can be useful to identify patients with active IgAN/HSPN.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01DOI: 10.1016/j.bbacli.2016.03.004
Rodolfo Tonin , Anna Caciotti , Silvia Funghini , Elisabetta Pasquini , Sean D. Mooney , Binghuang Cai , Elena Proncopio , Maria Alice Donati , Federico Baronio , Ilaria Bettocchi , Alessandra Cassio , Giacomo Biasucci , Andrea Bordugo , Giancarlo la Marca , Renzo Guerrini , Amelia Morrone
Short-chain acyl-coA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation caused by ACADS gene alterations. SCADD is a heterogeneous condition, sometimes considered to be solely a biochemical condition given that it has been associated with variable clinical phenotypes ranging from no symptoms or signs to metabolic decompensation occurring early in life.
A reason for this variability is due to SCAD alterations, such as the common p.Gly209Ser, that confer a disease susceptibility state but require a complex multifactorial/polygenic condition to manifest clinically.
Our study focuses on 12 SCADD patients carrying 11 new ACADS variants, with the purpose of defining genotype–phenotype correlations based on clinical data, metabolite evaluation, molecular analyses, and in silico functional analyses.
Interestingly, we identified a synonymous variant, c.765G > T (p.Gly255Gly) that influences ACADS mRNA splicing accuracy. mRNA characterisation demonstrated that this variant leads to an aberrant splicing product, harbouring a premature stop codon.
Molecular analysis and in silico tools are able to characterise ACADS variants, identifying the severe mutations and consequently indicating which patients could benefit from a long term follow- up. We also emphasise that synonymous mutations can be relevant features and potentially associated with SCADD.
{"title":"Clinical relevance of short-chain acyl-CoA dehydrogenase (SCAD) deficiency: Exploring the role of new variants including the first SCAD-disease-causing allele carrying a synonymous mutation","authors":"Rodolfo Tonin , Anna Caciotti , Silvia Funghini , Elisabetta Pasquini , Sean D. Mooney , Binghuang Cai , Elena Proncopio , Maria Alice Donati , Federico Baronio , Ilaria Bettocchi , Alessandra Cassio , Giacomo Biasucci , Andrea Bordugo , Giancarlo la Marca , Renzo Guerrini , Amelia Morrone","doi":"10.1016/j.bbacli.2016.03.004","DOIUrl":"10.1016/j.bbacli.2016.03.004","url":null,"abstract":"<div><p>Short-chain acyl-coA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation caused by <em>ACADS</em> gene alterations. SCADD is a heterogeneous condition, sometimes considered to be solely a biochemical condition given that it has been associated with variable clinical phenotypes ranging from no symptoms or signs to metabolic decompensation occurring early in life.</p><p>A reason for this variability is due to SCAD alterations, such as the common p.Gly209Ser, that confer a disease susceptibility state but require a complex multifactorial/polygenic condition to manifest clinically.</p><p>Our study focuses on 12 SCADD patients carrying 11 new <em>ACADS</em> variants, with the purpose of defining genotype–phenotype correlations based on clinical data, metabolite evaluation, molecular analyses, and <em>in silico</em> functional analyses.</p><p>Interestingly, we identified a synonymous variant, c.765G<!--> <!-->><!--> <!-->T (p.Gly255Gly) that influences <em>ACADS</em> mRNA splicing accuracy. mRNA characterisation demonstrated that this variant leads to an aberrant splicing product, harbouring a premature stop codon.</p><p>Molecular analysis and <em>in silico</em> tools are able to characterise <em>ACADS</em> variants, identifying the severe mutations and consequently indicating which patients could benefit from a long term follow- up. We also emphasise that synonymous mutations can be relevant features and potentially associated with SCADD.</p></div>","PeriodicalId":72344,"journal":{"name":"BBA clinical","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbacli.2016.03.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54181303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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