9 research outputs found
Comorbidities as an Indication for Metabolic Surgery
Metabolic diseases, comprising type 2 diabetes mellitus
(T2DM), dyslipidemia, and non-alcoholic steatohepatitis
(NASH), are rapidly increasing worldwide. Conservative
medical therapy, including the newly available drugs,
has only limited effects and does neither influence survival or the development of micro- or macrovascular
complications, nor the progression of NASH to liver cirrhosis, nor the development of hepatocellular carcinomas in the NASH liver. In contrast, metabolic surgery is
very effective independent of the preoperative body
mass index (BMI) in reducing overall and cardiovascular
mortality in patients with T2DM. Furthermore, metabolic
surgery significantly reduces the development of microand macrovascular complications while being the most
effective therapy in order to achieve remission of T2DM
and to reach the targeted glycemic control. Importantly,
even existing diabetic complications such as nephropathy as well as the features of NASH can be reversed by
metabolic surgery. Here, we propose indications for metabolic surgery due to T2DM and NASH based on a simple but objective, disease-specific staging system. We
outline the use of the Edmonton Obesity Staging System
(EOSS) as a clinical staging system independent of the
BMI that will identify patients who will benefit the most
from metabolic surgery
Comorbidities as an Indication for Metabolic Surgery
Metabolic diseases, comprising type 2 diabetes mellitus
(T2DM), dyslipidemia, and non-alcoholic steatohepatitis
(NASH), are rapidly increasing worldwide. Conservative
medical therapy, including the newly available drugs,
has only limited effects and does neither influence survival or the development of micro- or macrovascular
complications, nor the progression of NASH to liver cirrhosis, nor the development of hepatocellular carcinomas in the NASH liver. In contrast, metabolic surgery is
very effective independent of the preoperative body
mass index (BMI) in reducing overall and cardiovascular
mortality in patients with T2DM. Furthermore, metabolic
surgery significantly reduces the development of microand macrovascular complications while being the most
effective therapy in order to achieve remission of T2DM
and to reach the targeted glycemic control. Importantly,
even existing diabetic complications such as nephropathy as well as the features of NASH can be reversed by
metabolic surgery. Here, we propose indications for metabolic surgery due to T2DM and NASH based on a simple but objective, disease-specific staging system. We
outline the use of the Edmonton Obesity Staging System
(EOSS) as a clinical staging system independent of the
BMI that will identify patients who will benefit the most
from metabolic surgery
Comorbidities as an Indication for Metabolic Surgery
Metabolic diseases, comprising type 2 diabetes mellitus
(T2DM), dyslipidemia, and non-alcoholic steatohepatitis
(NASH), are rapidly increasing worldwide. Conservative
medical therapy, including the newly available drugs,
has only limited effects and does neither influence survival or the development of micro- or macrovascular
complications, nor the progression of NASH to liver cirrhosis, nor the development of hepatocellular carcinomas in the NASH liver. In contrast, metabolic surgery is
very effective independent of the preoperative body
mass index (BMI) in reducing overall and cardiovascular
mortality in patients with T2DM. Furthermore, metabolic
surgery significantly reduces the development of microand macrovascular complications while being the most
effective therapy in order to achieve remission of T2DM
and to reach the targeted glycemic control. Importantly,
even existing diabetic complications such as nephropathy as well as the features of NASH can be reversed by
metabolic surgery. Here, we propose indications for metabolic surgery due to T2DM and NASH based on a simple but objective, disease-specific staging system. We
outline the use of the Edmonton Obesity Staging System
(EOSS) as a clinical staging system independent of the
BMI that will identify patients who will benefit the most
from metabolic surgery
Antiâinflammatory mechanisms in cancer research: Characterization of a distinct M2âlike macrophage model derived from the THPâ1 cell line
Abstract Aims Macrophages play an essential role in cancer development. Tumorâassociated macrophages (TAMs) have predominantly M2âlike attributes that are associated with tumor progression and poor patient survival. Numerous methods have been reported for differentiating and polarizing macrophages in vitro, but there is no standardized and validated model for creating TAMs. Primary cells show varying cytokine responses depending on their origin and functional studies utilizing these cells may lack generalization and validity. A distinct cell lineâderived TAMâlike M2 subtype is required to investigate the mechanisms mediated by antiâinflammatory TAMs in vitro. Our previous work demonstrated a standardized protocol for creating an M2 subtype derived from a human THPâ1 cell line. The cell expression profile, however, has not been validated. The aim of this study was to characterize and validate the TAMâlike M2 subtype macrophage created based on our protocol to introduce them as a standardized model for cancer research. Methods and results Using qRTâPCR and ELISA, we demonstrated that proinflammatory, antiâinflammatory, and tumorâassociated marker expression changed during THPâ1âderived marcrophage development in vitro, mimicking a TAMârelated profile (e.g., TNFα, ILâ1ÎČ). The antiâinflammatory marker ILâ8/CXCL8, however, is most highly expressed in young M0 macrophages. Flow cytometry showed increased expression of CD206 in the final TAMâlike M2 macrophage. Singleâcell RNAâsequencing analysis of primary human monocytes and colon cancer tissue macrophages demonstrated that cell lineâderived M2 macrophages resembled a TAMârelated gene profile. Conclusions The THPâ1âderived M2 macrophage based on a standardized cell line model represents a distinct antiâinflammatory TAMâlike phenotype with an M2a subtype profile. This model may provide a basis for in vitro investigation of functional mechanisms in a variety of antiâinflammatory settings, particularly colon cancer development
Meta-analysis of metabolic surgery versus medical treatment for macrovascular complications and mortality in patients with type 2 diabetes
Serum uromodulin and Roux-en-Y gastric bypass: improvement of a marker reflecting nephron mass
Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing
Epigenetic alterations, that is, disruption of DNA methylation and chromatin architecture, are now acknowledged as a universal feature of tumorigenesis. Medulloblastoma, a clinically challenging, malignant childhood brain tumour, is no exception. Despite much progress from recent genomics studies, with recurrent changes identified in each of the four distinct tumour subgroups (WNT-pathway-activated, SHH-pathway-activated, and the less-well-characterized Group 3 and Group 4), many cases still lack an obvious genetic driver. Here we present whole-genome bisulphite-sequencing data from thirty-four human and five murine tumours plus eight human and three murine normal controls, augmented with matched whole-genome, RNA and chromatin immunoprecipitation sequencing data. This comprehensive data set allowed us to decipher several features underlying the interplay between the genome, epigenome and transcriptome, and its effects on medulloblastoma pathophysiology. Most notable were highly prevalent regions of hypomethylation correlating with increased gene expression, extending tens of kilobases downstream of transcription start sites. Focal regions of low methylation linked to transcription-factor-binding sites shed light on differential transcriptional networks between subgroups, whereas increased methylation due to re-normalization of repressed chromatin in DNA methylation valleys was positively correlated with gene expression. Large, partially methylated domains affecting up to one-third of the genome showed increased mutation rates and gene silencing in a subgroup-specific fashion. Epigenetic alterations also affected novel medulloblastoma candidate genes (for example, LIN28B), resulting in alternative promoter usage and/or differential messenger RNA/microRNA expression. Analysis of mouse medulloblastoma and precursor-cell methylation demonstrated a somatic origin for many alterations. Our data provide insights into the epigenetic regulation of transcription and genome organization in medulloblastoma pathogenesis, which are probably also of importance in a wider developmental and disease contex