Yam Code
Sign up
Login
New paste
Home
Trending
Archive
English
English
Tiếng Việt
भारत
Sign up
Login
New Paste
Browse
Gain-of-function mutation of SHP2 is a central regulator in tumorigenesis and cancer progression through cell-autonomous mechanisms. Activating mutation of SHP2 in microenvironment was identified to promote cancerous transformation of hematopoietic stem cell in non-autonomous mechanisms. It is interesting to see whether therapies directed against SHP2 in tumor or microenvironmental cells augment antitumor efficacy. In this review, we summarized different types of gain-of-function SHP2 mutations from a human disease. In general, gain-of-function mutations destroy the auto-inhibition state from wild-type SHP2, leading to consistency activation of SHP2. We illustrated how somatic or germline mutation of SHP2 plays an oncogenic role in tumorigenesis, stemness maintenance, invasion, etc. Moreover, the small-molecule SHP2 inhibitors are considered as a potential strategy for enhancing the efficacy of antitumor immunotherapy and chemotherapy. We also discussed the interconnection between phase separation and activating mutation of SHP2 in drug resistance of antitumor therapy.Across the animal kingdom, macrophages are known for their functions in innate immunity, but they also play key roles in development and homeostasis. Recent insights from single cell profiling and other approaches in the invertebrate model organism Drosophila melanogaster reveal substantial diversity among Drosophila macrophages (plasmatocytes). Together with vertebrate studies that show genuine expression signatures of macrophages based on their organ microenvironments, it is expected that Drosophila macrophage functional diversity is shaped by their anatomical locations and systemic conditions. In vivo evidence for diverse macrophage functions has already been well established by Drosophila genetics Drosophila macrophages play key roles in various aspects of development and organogenesis, including embryogenesis and development of the nervous, digestive, and reproductive systems. Macrophages further maintain homeostasis in various organ systems and promote regeneration following organ damage and injury. The interdependence and interplay of tissues and their local macrophage populations in Drosophila have implications for understanding principles of organ development and homeostasis in a wide range of species.Thalidomide, a sedative drug that was once excluded from the market owing to its teratogenic properties, was later found to be effective in treating multiple myeloma. We had previously demonstrated that cereblon (CRBN) is the target of thalidomide embryopathy and acts as a substrate receptor for the E3 ubiquitin ligase complex, Cullin-Ring ligase 4 (CRL4CRBN) in zebrafish and chicks. CRBN was originally identified as a gene responsible for mild intellectual disability in humans. Fetuses exposed to thalidomide in early pregnancy were at risk of neurodevelopmental disorders such as autism, suggesting that CRBN is involved in prenatal brain development. Recently, we found that CRBN controls the proliferation of neural stem cells in the developing zebrafish brain, leading to changes in brain size. Our findings imply that CRBN is involved in neural stem cell growth in humans. Accumulating evidence shows that CRBN is essential not only for the teratogenic effects but also for the therapeutic effects of thalidomide. This review summarizes recent progress in thalidomide and CRBN research, focusing on the teratogenic and therapeutic effects. Investigation of the molecular mechanisms underlying the therapeutic effects of thalidomide and its derivatives, CRBN E3 ligase modulators (CELMoDs), reveals that these modulators provide CRBN the ability to recognize neosubstrates depending on their structure. Understanding the therapeutic effects leads to the development of a novel technology called CRBN-based proteolysis-targeting chimeras (PROTACs) for target protein knockdown. These studies raise the possibility that CRBN-based small-molecule compounds regulating the proliferation of neural stem cells may be developed for application in regenerative medicine.The current treatment for ocular pathological angiogenesis mainly focuses on anti-VEGF signals. This treatment has been confirmed as effective despite the unfavorable side effects and unsatisfactory efficiency. Recently, endothelial cell metabolism, especially glycolysis, has been attracting attention as a potential treatment by an increasing number of researchers. Emerging evidence has shown that regulation of endothelial glycolysis can influence vessel sprouting. This new evidence has raised the potential for novel treatment targets that have been overlooked for a long time. In this review, we discuss the process of endothelial glycolysis as a promising target and consider regulation of the enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase as treatment for ocular pathological angiogenesis.It is challenging to study heterotopic ossification (HO) in patients with fibrodysplasia ossificans progressiva (FOP) due to the contraindication of invasive techniques (i.e., bone biopsies), which can trigger flare-ups. The aim of this case study was to assess mature HO at the microarchitectural level non-invasively with high-resolution peripheral quantitative computed tomography (HR-pQCT). Depending on the patient's mobility, HR-pQCT scans were acquired of peripherally located HO and standard distal radius and tibia regions in two FOP patients, a 33-year-old woman and a 23-year-old man, with the classical mutation (p.R206H). HO was located around the halluces, the ankles, and in the Achilles tendon. Standard HR-pQCT analyses were performed of the distal radius, tibia, and HO to quantify bone mineral density (BMD) and bone microarchitecture. Micro-finite element analysis was used to estimate failure load (FL). The outcomes were compared between HO and neighboring skeletal bone and with an age- and gender-matn the peripheral skeleton of the FOP patients. HO and skeleton also appear to be able to become one entity when contiguous.Interpreting connections between the multiple networks of cell metabolism is indispensable for understanding how cells maintain homeostasis or transform into the decontrolled proliferation phenotype of cancer. Situated at a critical metabolic intersection, citrate, derived via glycolysis, serves as either a combustible fuel for aerobic mitochondrial bioenergetics or as a continuously replenished cytosolic carbon source for lipid biosynthesis, an essentially anaerobic process. https://www.selleckchem.com/products/l-arginine-l-glutamate.html Therein lies the paradox under what conditions do cells control the metabolic route by which they process citrate? The Warburg effect exposes essentially the same dilemma-why do cancer cells, despite an abundance of oxygen needed for energy-generating mitochondrial respiration with citrate as fuel, avoid catabolizing mitochondrial citrate and instead rely upon accelerated glycolysis to support their energy requirements? This review details the genesis and consequences of the metabolic paradigm of a "truncated" Krebs/TCA cycle. Abundant data are presented for substrate utilization and membrane cholesterol enrichment in tumors that are consistent with criteria of the Warburg effect.
Paste Settings
Paste Title :
[Optional]
Paste Folder :
[Optional]
Select
Syntax Highlighting :
[Optional]
Select
Markup
CSS
JavaScript
Bash
C
C#
C++
Java
JSON
Lua
Plaintext
C-like
ABAP
ActionScript
Ada
Apache Configuration
APL
AppleScript
Arduino
ARFF
AsciiDoc
6502 Assembly
ASP.NET (C#)
AutoHotKey
AutoIt
Basic
Batch
Bison
Brainfuck
Bro
CoffeeScript
Clojure
Crystal
Content-Security-Policy
CSS Extras
D
Dart
Diff
Django/Jinja2
Docker
Eiffel
Elixir
Elm
ERB
Erlang
F#
Flow
Fortran
GEDCOM
Gherkin
Git
GLSL
GameMaker Language
Go
GraphQL
Groovy
Haml
Handlebars
Haskell
Haxe
HTTP
HTTP Public-Key-Pins
HTTP Strict-Transport-Security
IchigoJam
Icon
Inform 7
INI
IO
J
Jolie
Julia
Keyman
Kotlin
LaTeX
Less
Liquid
Lisp
LiveScript
LOLCODE
Makefile
Markdown
Markup templating
MATLAB
MEL
Mizar
Monkey
N4JS
NASM
nginx
Nim
Nix
NSIS
Objective-C
OCaml
OpenCL
Oz
PARI/GP
Parser
Pascal
Perl
PHP
PHP Extras
PL/SQL
PowerShell
Processing
Prolog
.properties
Protocol Buffers
Pug
Puppet
Pure
Python
Q (kdb+ database)
Qore
R
React JSX
React TSX
Ren'py
Reason
reST (reStructuredText)
Rip
Roboconf
Ruby
Rust
SAS
Sass (Sass)
Sass (Scss)
Scala
Scheme
Smalltalk
Smarty
SQL
Soy (Closure Template)
Stylus
Swift
TAP
Tcl
Textile
Template Toolkit 2
Twig
TypeScript
VB.Net
Velocity
Verilog
VHDL
vim
Visual Basic
WebAssembly
Wiki markup
Xeora
Xojo (REALbasic)
XQuery
YAML
HTML
Paste Expiration :
[Optional]
Never
Self Destroy
10 Minutes
1 Hour
1 Day
1 Week
2 Weeks
1 Month
6 Months
1 Year
Paste Status :
[Optional]
Public
Unlisted
Private (members only)
Password :
[Optional]
Description:
[Optional]
Tags:
[Optional]
Encrypt Paste
(
?
)
Create New Paste
You are currently not logged in, this means you can not edit or delete anything you paste.
Sign Up
or
Login
Site Languages
×
English
Tiếng Việt
भारत