Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy
The licensed drug rapamycin has the potential to be repurposed for geriatric protection. A key challenge is avoiding the undesirable side effects of continuous dosing. The findings suggest that the geriatric protective effects of chronic rapamycin treatment can be obtained with brief drug pulses during early adulthood in female flies and mice. In Drosophila, brief early rapamycin treatment in adults extended lifespan and reduced age-related gut decline to the same extent as lifelong administration. Long-lasting memory of early treatment was mediated by enhanced autophagy in enterocytes, accompanied by elevated intestinal LManV and lysozyme levels. The transient elevation of autophagy in early adulthood itself induces a long-term increase in autophagy. In mice, 3 months of early treatment induced memory effects even after 6 months of rapamycin discontinuation, maintaining lysozyme distribution, Man2B1 levels in intestinal crypts, Paneth cells similar to chronic treatment Structure and intestinal barrier function.
3X Flag peptide
Flag peptide is the peptide sequence of amino acids, which is hydrophilic and has high immunogenicity. These are fusion peptides that are used as tags to detect the target molecule either protein or protein complexes for their rapid purification. It is consisting of almost 8 amino acids (DYKDDDDK) which are sequenced in a specific manner. These flag peptides are of small size; hence they are encoded by a short oligonucleotide sequence. Normally the last 5 sequences of amino acids serve as a specific cleavage site of an enzyme called enterokinase, that in turn allows the removal of the tag peptide. Depending upon the functions or applications of the flag peptide, it may either combine with the N or C terminal of the protein. The N-terminal of the given flag peptide has an affinity to bind with the monoclonal antibodies which are called anti-flag antibodies. The complex which is formed between the flag peptide and the monoclonal antibody is Ca2+ dependent. Which can be broken by any chelating agent like EDTA. Some studies contradict this concept by saying that the fusion between the flag peptide and the monoclonal antibodies M1 (Also called anti-flag antibodies) is not Ca2+ dependent.
Janus AuNR-Pt Nanoscale Motors for Enhanced NIR-II Photoacoustic Imaging of Deep Tumors and Pt2+ Ion-related Chemotherapy
Nanomotors have active locomotion capabilities and thus have great potential for deep tissue imaging and in vivo drug delivery. The use of nanomotors with particle sizes smaller than 100 nm for in vivo imaging and therapy is one of the core innovations in this field. Here, hydrogen peroxide (H2O2)-driven nanoscale Janus gold nanorod-platinum (JAuNR-Pt) nanomotors were used to enhance the effectiveness of NIR-II for area photoacoustic (PA) imaging and tumor therapy in deep tumor tissues . The JAuNR-Pt nanomotors deposited a platinum Pt shell on one end of the gold nanorods with coverages including 10%, 25%, 50%, 75%, and 100%. Among them, the JAuNR-Pt nanomotor with 50% platinum shell coverage exhibits the highest diffusion coefficient (De) and can move rapidly in the presence of hydrogen peroxide. Self-propulsion of JAuNR-Pt nanomotors enhanced cellular uptake, accelerated lysosomal escape, and facilitated sustained release. Cytotoxic Pt2+ ions enter the nucleus, leading to DNA damage and apoptosis. JAuNR-Pt nanomotors exhibited deep penetration and accumulation in tumors and high tumor therapeutic efficacy. Therefore, the findings of this study demonstrate significant tumor imaging and antitumor effects, providing an effective strategy for accurate diagnosis and treatment of the disease.
Lipo3000 Transfection Reagent
Lipo3000 is a type of transfection reagent which is lipid-based in nature and used to transfect cells by transporting the complex molecules into the cell. Due to its cationic nature, it is used in a wide variety of techniques i.e. gene expression or gene delivery.
3BDO Successfully Inhibits Glioblastoma Growth in Vitro and in Vivo
Glioblastoma (GBM) is a high-grade glioma characterized by a high rate of invasiveness and rapid growth. Despite advances in surgical and medical treatment modalities, very few patients with GBM survive beyond 15 months after diagnosis. Currently, temozolomide (TMZ) is the main first-line drug for GBM chemotherapy, but it is prone to drug resistance. Therefore, it is urgent to identify other drugs with better efficacy to treat GBM.
Lipo2000 Transfection Reagent
It is a type of reagent that is cationic, liposome-based, and used in a wide variety of in-vitro techniques in mammalian cells for transfection, and transgene expressions. The efficiency of transfection and viability of cell depends upon many factors which are given as follows:
• Media components (antibiotics & serum level)
• Liposome
• Cell density
• DNA-liposome complexing time
• DNA concentration
D-luciferin
D-Luciferin is basically a substrate for many metabolic enzymes. It is used in different techniques like assays in which it is used to measure luciferase enzymes in the presence of adenosine triphosphate (ATP). Almost all the bioluminescence insects have specific types of luciferase enzymes but all they share a common substrate called D luciferin which is present in almost 40 different species of beetles or firefly insects(White et al., 1963, De Wet et al., 1985). It has a wide variety of applications, but more commonly it is a bioluminescent agent which is used in different in-vivo and in-vitro research related to stem cells, gene expression, growth of cancer, etc.
FERROSTATIN 1
As we know, in general, reactive Oxygen species (ROS) are essential for the normal biological functions of cells but on other hand, they are also involved in cellular degeneration and tissue death. So, there is a basic need for such chemical or compound which is antioxidant in nature and very specific in its functions to combat the production of ROS (which induces cellular death) without altering the production of normal ROS that are required for cellular functions. That’s why Ferostatin-1 is developed. It is a very potent chemical agent for inhibiting ferroptosis which is defined as an oxidative, somewhat regulated, and nonapoptotic death of a cell.
Small Molecule Inhibition of METTL3 as a Strategy for the Treatment of Myeloid Leukemia
n6-methyladenosine (m6A) is an internal RNA-modifying enzyme primarily catalyzed by the METTL3-METTL14 methyltransferase complex. The m6A methyltransferase METTL3 has been implicated in the initiation and maintenance of acute myeloid leukemia (AML), but the potential application of targeting this enzyme remains unclear. Here, we present the identification and characterization of STM2457 and the crystal structure of STM2457 in complex with METTL3-METTL14. STM2457 is a potent and selective METTL3 catalytic inhibitor, and tumor treatment with STM2457 resulted in decreased AML growth and increased differentiation and apoptosis. Concomitant with selective reduction of m6A levels of leukemic mRNAs, expression consistent with translational defects was reduced. The investigators demonstrated that METTL3 inhibition in vivo resulted in impaired engraftment and prolonged survival in various mouse models of AMTL, particularly targeting key stem cell subsets of AML. Collectively, these results reveal METTL3 inhibition as a potential therapeutic strategy against AML, and targeting of RNA-modifying enzymes is a promising anticancer therapeutic avenue.
Immune cells use ghrelin to promote wound healing
When people are hungry, the stomach produces Ghrelin, which makes people feel hungry and promotes appetite, and after eating, fat cells produce Leptin, which makes people feel full and suppresses appetite. This homeostasis between ghrelin and leptin has long been thought to be critical for metabolism and diet.