Adamsendaley3951
Injection of this viscous emulsion on the back of the neck is followed by a single intraperitoneal injection of Bordetella pertussis toxin. At the onset of symptoms (day 12-14) and under general anesthesia, fundoscopic images are taken to assess disease progression through clinical examination. These data can be directly compared with those at later timepoints and peak disease (day 20-22) with differences analyzed. At the same time, this protocol allows the investigator to assess potential differences in vessel permeability and damage using fluorescein angiography. EAU can be induced in other mouse strains - both wildtype or genetically modified - and combined with novel therapies offering flexibility for studying drug efficacy and/or disease mechanisms.Multiphoton microscopy techniques, such as two-photon microscopy (2PM) and three-photon microscopy (3PM), are powerful tools for deep-tissue in vivo imaging with subcellular resolution. 3PM has two major advantages for deep-tissue imaging over 2PM that has been widely used in biology laboratories (i) longer attenuation length in scattering tissues by employing ~1,300 nm or ~1,700 nm excitation laser; (ii) less background fluorescence generation due to higher-order nonlinear excitation. As a result, 3PM allows high-contrast structural and functional imaging deep within scattering tissues such as intact mouse brain from the cortical layers to the hippocampus and the entire forebrain of adult zebrafish. Today, laser sources suitable for 3PM are commercially available, enabling the conversion of an existing two-photon (2P) imaging system to a three-photon (3P) system. Additionally, multiple commercial 3P microscopes are available, which makes this technique readily available to biology research laboratories. This paper shows the optimization of a typical 3PM setup, particularly targeting biology groups that already have a 2P setup, and demonstrates intravital 3D imaging in intact mouse and adult zebrafish brains. This protocol covers the full experimental procedure of 3P imaging, including microscope alignment, prechirping of ~1,300 and ~1,700 nm laser pulses, animal preparation, and intravital 3P fluorescence imaging deep in adult zebrafish and mouse brains.
Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related deaths. Of the various established risk factors for this aggressive condition, diet is a notable modifiable risk factor. This review aims to summarize the mounting evidence to suggest the role of diet, the microbiota and their cross-talk in modulating an individual's risk of developing CRC.
Specifically, the metabolism of bile acids and its symbiosis with the microbiota has gained weight given its basis on a high meat, high fat, and low fibre diet that is present in populations with the highest risk of CRC. Bacteria modify bile acids that escape enterohepatic circulation to increase the diversity of the human bile acid pool. The production of microbial bile acids contributes to this as well. Epidemiological studies have shown that changing the diet results in different levels and composition of bile acids, which has in turn modified the risk of CRC at a population level. Evidence to identify underlying mechanisms have tied into the microbiota-led digestions of various foods into fatty acids that feedback into bile acid physiology as well as modulation of endogenous receptors for bile acids.
There is adequate evidence to support the role of microbiota in in the metabolism of bile acids, and how this relates to colorectal cancer. Further work is necessary to identify specific bacteriome involved and their underlying mechanistic pathways.
There is adequate evidence to support the role of microbiota in in the metabolism of bile acids, and how this relates to colorectal cancer. Further work is necessary to identify specific bacteriome involved and their underlying mechanistic pathways.
Dietary fiber intake in IBD patients has oftentimes generated conflicting data and clinical recommendations. This review aims to unify apparently conflicting lines of evidence regarding dietary fiber intake in IBD patients by highlighting new information from natural history studies and prospective clinical trials.
IBD patients have lower dietary fiber intake than the general population as well as national guideline recommendations. Patients report short-term benefits from fiber avoidance. Low fiber and low FODMAP diets are associated with lower fecal microbiota abundance and essential nutrient intake. There is emerging evidence suggesting that IBD patients may be able to increase dietary fiber intake with short-term benefit and good tolerability, particularly when fiber is introduced during clinical remission. Current societal recommendations do not favor withholding dietary fiber during long-term IBD management. The long-term impact of increased dietary fiber on IBD clinical outcomes remains unanswered.
Dietary fiber intake is not necessarily contraindicated in IBD patients.
Dietary fiber intake is not necessarily contraindicated in IBD patients.
Lipid metabolism presents a targetable metabolic vulnerability in colorectal cancer (CRC). Lipid signatures and cancer-cell lipid requirements may serve as noninvasive diagnostic and prognostic biomarkers and as a therapeutic target, respectively.
A growing body of new studies highlight the complexity of lipid metabolism in CRC. Cancer cells are able to utilize an alternative fatty acid desaturation pathway, underlining the metabolic plasticity of tumors. CRC tissue shows a robust triglyceride-species signature with prognostic value in CRC patients. Lipidomic analyses in germfree and colonized mice identify a unique lipid signature and suggest that bacteria inhibit metabolism of polyunsaturated fatty acids by blocking desaturase and elongase activities. Cellular stress responses, particularly the well characterized unfolded protein response, are involved in regulating lipid synthesis and homeostasis, and contribute to adaptation of the lipid environment. Together, lipid metabolism, the intestinal microbiota and cellular stress responses unarguably play crucial roles in CRC.
A number of recent advances in our understanding of dysregulated lipid metabolism in CRC underline the importance of this research field. An improved knowledge of the complex interplay between lipid metabolism, cellular stress and the intestinal microbiota in the context of CRC may lead to novel therapeutic strategies.
A number of recent advances in our understanding of dysregulated lipid metabolism in CRC underline the importance of this research field. An improved knowledge of the complex interplay between lipid metabolism, cellular stress and the intestinal microbiota in the context of CRC may lead to novel therapeutic strategies.
Gastric cancer is one of the leading causes of cancer-related deaths globally. Several modifiable environmental factors have been linked to gastric carcinogenesis but in many cases, evidence is either weak or fragmented. In this review, we interrogate the latest evidence implicating environmental factors in the development of gastric cancer.
We are writing this review at a time when technological advancements are enabling scientists to effectively conduct large epidemiological studies with better tools for exposure estimations. We have highlighted risk factors that do not yet have enough evidence to be included as definite carcinogens in the International Agency for Research on Cancer monographs but have the potential for inclusion in the near future. Considered in our review are the links between gastric cancer and exposure to biomass smoke, particulate matter, occupational hazards and water contamination.
This review illustrates the need for vigilance as evidence linking gastric cancer to various environmental factors is mounting. Many of these factors are modifiable, allowing for preventive strategies that could further decrease the global burden of gastric cancer.
This review illustrates the need for vigilance as evidence linking gastric cancer to various environmental factors is mounting. Many of these factors are modifiable, allowing for preventive strategies that could further decrease the global burden of gastric cancer.
The purpose of this symposium was to bring thought leaders in the microbiome from the west to Africa to share their unique experiences with African investigators in order to build the foundations for scientifically rigorous explorations into the African human and environmental microbiome that may explain why disease patterns are different in Africa where the chief killers are infectious diseases, whereas noncommunicable diseases (NCDs) are the major threat to healthcare resources in the developed world.
The application of new high throughput technologies to the investigation of the microbiome and its metabolome has revealed mechanisms whereby a traditional African high fiber diet can suppress NCDs which include colon cancer, inflammatory bowel diseases, obesity, type 2 diabetes and atherosclosis. There is concern that with migration and westernization, NCDs are becoming more common in Africa and that food security is becoming impaired by unbalanced obesogenic foods rather than inadequate food intake.
There is an urgent need for the formation of combined African-Western research programs to identify what is good and bad in the African diet-microbiome axis to develop strategies to prevent the incidence of NCDs rising to western levels in Africa, at the same time offering novel prevention strategies against the #1 healthcare threat in the developed world.
There is an urgent need for the formation of combined African-Western research programs to identify what is good and bad in the African diet-microbiome axis to develop strategies to prevent the incidence of NCDs rising to western levels in Africa, at the same time offering novel prevention strategies against the #1 healthcare threat in the developed world.
Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) among others, have attracted a great deal of attention for their potential role as master regulators of gene expression and as therapeutic targets. This review focuses on recent advances on the role of ncRNAs in the pathogenesis, diagnosis and treatment of diseases of the cholangiocytes (i.e. cholangiopathies).
In the recent years, there has been an exponential growth in the knowledge on ncRNAs and their role in cholangiopathies, particularly cholangiocarcinoma.
Although several studies focused on miRNAs as noninvasive biomarkers for diagnosis and staging, several studies also highlighted their functions and provided new insights into disease mechanisms.
Although several studies focused on miRNAs as noninvasive biomarkers for diagnosis and staging, several studies also highlighted their functions and provided new insights into disease mechanisms.
Cellular senescence (i.e. permanent withdrawal from the cell cycle) is increasingly recognized as a pathologic feature in a variety of inflammatory liver diseases, including primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and additional cholangiopathies. Herein, we provide an update on the interplay between cholangiocytes, cellular senescence and the cholangiopathies.
The themes covered by this review include novel models for studying the role of senescent cholangiocytes and the cholangiopathies, identification and modulation of key pathways or molecules regulating cholangiocyte senescence, and discovery of druggable targets to advance therapeutic options for the cholangiopathies. AZD4547 Most recent studies focused on PSC; however, the concepts and findings may be applied to additional cholangiopathies.
Cholangiopathies present unique and divergent clinicopathological features, causes and genetic backgrounds, but share several common disease processes. Cholangiocyte senescence in the cholestatic cholangiopathies, primarily PSC and PBC, is regarded as a key pathogenetic process.
