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PubMed Journals Articles About "STAT Plus Small Drug Maker Make Amends With" RSS

17:22 EDT 21st September 2019 | BioPortfolio

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Showing "STAT Plus small drug maker make amends with" PubMed Articles 1–25 of 20,000+

First Measurement of the Form Factors in D_{s}^{+}→K^{0}e^{+}ν_{e} and D_{s}^{+}→K^{*0}e^{+}ν_{e} Decays.

We report on new measurements of Cabibbo-suppressed semileptonic D_{s}^{+} decays using 3.19  fb^{-1} of e^{+}e^{-} annihilation data sample collected at a center-of-mass energy of 4.178 GeV with the BESIII detector at the BEPCII collider. Our results include branching fractions B(D_{s}^{+}→K^{0}e^{+}ν_{e})=[3.25±0.38(stat)±0.16(syst)]×10^{-3} and B(D_{s}^{+}→K^{*0}e^{+}ν_{e})=[2.37±0.26(stat)±0.20(syst)]×10^{-3}, which are much improved relative to previous measurements, and the first meas...


Let's get small (and smaller): Combining zebrafish and nanomedicine to advance neuroregenerative therapeutics.

Several key attributes of zebrafish make them an ideal model system for the discovery and development of regeneration promoting therapeutics; most notably their robust capacity for self-repair which extends to the central nervous system. Further, by enabling large-scale drug discovery directly in living vertebrate disease models, zebrafish circumvent critical bottlenecks which have driven drug development costs up. This review summarizes currently available zebrafish phenotypic screening platforms, HTS-read...

Making Amends for the Opioid Epidemic.


Measurement of the Dynamics of the Decays D_{s}^{+}→η^{(')}e^{+}ν_{e}.

Using e^{+}e^{-} annihilation data corresponding to an integrated luminosity of 3.19  fb^{-1} collected at a center-of-mass energy of 4.178 GeV with the BESIII detector, we measure the absolute branching fractions B_{D_{s}^{+}→ηe^{+}ν_{e}}=(2.323±0.063_{stat}±0.063_{syst})% and B_{D_{s}^{+}→η^{'}e^{+}ν_{e}}=(0.824±0.073_{stat}±0.027_{syst})% via a tagged analysis technique, where one D_{s} is fully reconstructed in a hadronic mode. Combining these measurements with previous BESIII measureme...

Dysfunctional Lens Index Serves as a Novel Surgery Decision-Maker for Age-Related Nuclear Cataracts.

To study the correlations between subjective and objective cataract metrics with dysfunctional lens index. To investigate the potential of the DLI as a novel surgery decision-maker.

JAK/STAT pathway modulation: Does it work in Dermatology?

JAK/STAT is an intracellular signaling pathway, which plays a key role in downstream transmission of extracellular signals from cell membrane to the cell nucleus. This pathway is activated by cytokines, which participate in inflammation, innate and acquired immune responses, and also cell growth. Recent studies point out possible disturbances in JAK/STAT pathway in various inflammatory and autoimmune skin diseases, such as atopic dermatitis, psoriasis, alopecia areata. Various molecules that modulate - inhi...

A JAK-STAT pathway target gene encoding a single WAP domain (SWD)-containing protein from Litopenaeus vannamei.

In shrimp, the JAK-STAT pathway is essentially implicated in both antiviral and antibacterial responses. However, few regulatory target genes of the JAK-STAT pathway in shrimp have been reported so far. In this study, a novel single WAP domain-containing peptide (LvSWD4) was identified from Pacific white shrimp Litopenaeus vannamei. The promoter of LvSWD4 was predicted to harbor multiple STAT-binding DNA motifs. Over-expression of the JAK-STAT pathway components STAT, JAK and Domeless in vitro significantly...

In vitro digestion models to evaluate lipid based drug delivery systems; present status and current trends.

During the past two decades, a range of in vitro models simulating the digestion processes occurring in the stomach and small intestine have been developed to characterize lipid based drug delivery systems (LbDDSs). This review describes the presently existing range of in vitro digestion models and their use in the field of oral drug delivery. The models are evaluated in terms of their suitability to assess LbDDSs, and their ability to produce in vitro - in vivo correlations (IVIVCs). While the pH-stat lipo...

Inverse pharmacology: Approaches and tools for introducing druggability into engineered proteins.

A major feature of twenty-first century medical research is the development of therapeutic strategies that use 'biologics' (large molecules, usually engineered proteins) and living cells instead of, or as well as, the small molecules that were the basis of pharmacology in earlier eras. The high power of these techniques can bring correspondingly high risk, and therefore the need for the potential for external control. One way of exerting control on therapeutic proteins is to make them responsive to small mo...

Interstitial Lung Disease Induced by Crizotinib in Non-Small-Cell Lung Cancer.

The treatment of advanced non-small-cell lung cancer shifted with the development of molecular-targeted therapies, like the tyrosine kinase inhibitors. One example of tyrosine kinase inhibitors is crizotinib, an anaplastic lymphoma tyrosine kinase inhibitor, which targets an echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase gene fusion. This mutation is found in only 2% to 7% of non-small-cell lung cancer cases. Although these new therapies have shown promising results, the occu...

Gene and protein expression profiles of JAK-STAT signalling pathway in the developing brain of the Ts1Cje Down syndrome mouse model.

The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Therefore, we aimed to profile the expression of Jak1, Jak2, Stat1,...

Psychotropic drug use in residents with dementia living in small-scaled special care facilities; a longitudinal study.

Over the past decade, a trend has been noticed in the Netherlands to replace large-scaled special care units (SCUs) caring for 20-30 residents with dementia by small-scaled SCUs caring for up to 8 residents. Systematic evaluations, however, have yielded a differentiated picture of the effects. As the impact on psychotropic drug use has hardly been addressed thus far, we examined the (potential) impact of psychotropic drug use when moving residents with dementia from large-scaled to small-scaled SCUs.

Early Optic Nerve Head Glial Proliferation and Jak-Stat Pathway Activation in Chronic Experimental Glaucoma.

We previously reported increased expression of cell proliferation and Jak-Stat pathway-related genes in chronic experimental glaucoma model optic nerve heads (ONH) with early, mild injury. Here, we confirm these observations by localizing, identifying, and quantifying ONH cellular proliferation and Jak-Stat pathway activation in this model.

Microvesicles of osteoblasts modulate bone marrow mesenchymal stem cell-induced apoptosis to curcumin in myeloid leukemia cells.

Microvesicles (MVs) derived from bone marrow niche components have an important role in genetic reprogramming and subsequent drugs induce apoptosis in leukemic cells. Here, we have found that undertreatment of curcumin or daunorubicin, the cross-talk through MVs of KG-1-bone marrow mesenchymal stem cells (BMSCs), significantly downregulates the expression of the survival gene osteopontin (OPN), CXCL-12, IL-6 (interleukin-6), STAT-3, and VCAM-1 (vascular cell adhesion molecule 1) in treated-KG-1 cells as we...

Study of the D^{0}→K^{-}μ^{+}ν_{μ} Dynamics and Test of Lepton Flavor Universality with D^{0}→K^{-}ℓ^{+}ν_{ℓ} Decays.

Using e^{+}e^{-} annihilation data of 2.93  fb^{-1} collected at center-of-mass energy sqrt[s]=3.773  GeV with the BESIII detector, we measure the absolute branching fraction of D^{0}→K^{-}μ^{+}ν_{μ} with significantly improved precision: B_{D^{0}→K^{-}μ^{+}ν_{μ}}=(3.413±0.019_{stat}±0.035_{syst})%. Combining with our previous measurement of B_{D^{0}→K^{-}e^{+}ν_{e}}, the ratio of the two branching fractions is determined to be B_{D^{0}→K^{-}μ^{+}ν_{μ}}/B_{D^{0}→K^{-}e^{+}ν_{e...

Insect Neurobiology: What to Make of a Small Spot?

Vertical stripes have long been known to attract laboratory fruit flies, but small spots, presumably common in the wild, seemed only to avert them. A new study finds odor can reverse this, demonstrating that flies respond to shapes more judiciously than was thought.

Thermo-optic soliton routing in nematic liquid crystals: erratum.

This erratum amends some errors in Opt. Lett.43, 2296 (2018)OPLEDP0146-959210.1364/OL.43.002296.

Nanobodies detecting and modulating GPCRs outside in and inside out.

G protein-coupled receptors (GPCRs), belonging to the largest class of membrane proteins, play a prominent role in many (patho)physiological processes and are, therefore, important drug targets. Although most often targeted by small molecules, these receptors have become interesting targets for antibodies and antibody fragments, especially camelid-derived heavy chain-only antibodies and fragments thereof (nanobodies). The small size and molecular structure of nanobodies allow GPCR-binding and modulation, fr...

Application of Low-Frequency Raman Scattering Spectroscopy to Probe in Situ Drug Solubilization in Milk during Digestion.

We have recently shown that real-time monitoring of drug solubilization and changes to solid state of the drug during digestion of milk can be achieved using synchrotron small-angle X-ray scattering. A complementary laboratory-based method to explore such changes is low-frequency Raman spectroscopy, which has been increasingly used to characterize crystalline drugs and their polymorphs in powders and suspensions. This study investigates the use of this technique to monitor in situ drug solubilization in mi...

Characterization of in vitro Mrp2 transporter model based on intestinal organoids.

Multidrug resistance associated protein 2 (MRP2) is an important efflux transporter involved in clinical drug disposition and drug-drug interactions. The study of MRP2-mediated drug transport has become an integral part of drug discovery and development. In particular, screening of specific MRP2 inhibitors will help overcome the multidrug resistance in cancer. In this report, a new method for rapid and sensitive detection of Mrp2 function was established via using mouse small intestinal organoids. Firstly, ...

The new entries in the therapeutic armamentarium: the small molecule JAK inhibitors.

The past decade has witnessed an explosion in trial data on JAK inhibitors (JAKi). These small molecules target the Janus kinase - signal transducer and activator of transcription (JAK-STAT) pathway, blocking crucial cytokines across a septum of rheumatic diseases. As a class, JAKi are beginning to demonstrate efficacy on par, if not superior to biologics. Two first generation JAKi are licensed for use in inflammatory arthritis; tofacitinib and baricitinib. Next-generation JAKi have been designed with selec...

Alteration of Physicochemical Properties for Antibody Drug Conjugates and Their Impact on Stability.

Antibody conjugates, in particular antibody drug conjugates (ADC), are a fast-growing area in research and in the pharmaceutical industry. The covalent attachment of an antibody to a chemical moiety can be an effective measure for drug targeting or can also positively impact pharmacokinetics of small molecular compounds by serum half-life extension. Stability, physicochemical properties and degradation pathways of biotherapeutics or small molecule therapeutics are often not totally known and understood. How...

Modulation of Amyloid-β42 Conformation by Small Molecules Through Non-Specific Binding.

Aggregation of amyloid-β (Aβ) peptides is a crucial step in the progression of Alzheimer's disease (AD). Identifying aggregation inhibitors against AD has been a great challenge. We report an atomistic simulation study of the inhibition mechanism of two small molecules, homotaurine and -inositol, which are AD drug candidates currently under investigation. We show that both small molecules promote a conformational change of Aβ42 monomer toward a more collapsed phase through a non-specific binding mechanis...

Evaluation of the i-STAT analyzer for determination of ionized calcium concentrations in bovine blood.

Information regarding the performance of the i-STAT, a point-of-care analyzer, to determine ionized calcium (iCa ) concentration in bovine blood is limited.

Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction.

Protein-protein interactions (PPIs) governing the recognition of substrates by E3 ubiquitin ligases are critical to cellular function. There is significant therapeutic potential in the development of small molecules that modulate these interactions; however, rational design of small molecule enhancers of PPIs remains elusive. Herein, we report the prospective identification and rational design of potent small molecules that enhance the interaction between an oncogenic transcription factor, β-Catenin, and i...


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