UPLC-MS/MS Method for Givinostat in Rat Plasma: Development, Validation, in vivo Pharmacokinetics Study and in vitro Metabolic Stability Research.

Background: Givinostat, a potent histone deacetylase (HDAC) inhibitor, is promising for the treatment of relapsed leukemia and myeloma.

Purpose: This study aimed to develop and verify a quick assay for the measurement of givinostat concentration using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) with eliglustat as the internal standard (IS), establishing a basic pharmacokinetic profile for its pre-clinical application and metabolic stability in vitro.

Methods: Sample preparation was performed via protein precipitation using acetonitrile.

Involvement of P2X7R-mediated microglia polarization and neuroinflammation in the response to electroacupuncture on post-stroke memory impairment.

Purpose: Post-stroke cognitive impairment (PSCI) is a common complication of ischemic stroke episodes. Memory impairment is an important component of the poststroke cognitive syndrome. Microglial activation plays a critical role in stroke-induced neuroinflammation.

CD38 x ICAM-1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma.

The cluster of differentiation 38 (CD38) is a well-validated target for treating multiple myeloma. Although anti-CD38 mAbs have demonstrated outstanding initial responses in patients with multiple myeloma, nearly all patients eventually develop resistance and relapse. In addition, currently approved CD38 targeting therapies have failed to show monotherapy efficacy in lymphomas, where CD38 expression is present but at lower levels.

Modulation of entorhinal cortex-hippocampus connectivity and recognition memory following electroacupuncture on 3×Tg-AD model: Evidence from multimodal MRI and electrophysiological recordings.

Memory loss and aberrant neuronal network activity are part of the earliest hallmarks of Alzheimer's disease (AD). Electroacupuncture (EA) has been recognized as a cognitive stimulation for its effects on memory disorder, but whether different brain regions or neural circuits contribute to memory recovery in AD remains unknown. Here, we found that memory deficit was ameliorated in 3×Tg-AD mice with EA-treatment, as shown by the increased number of exploring and time spent in the novel object.

Flexibly Controlling the Polycrystallinity and Improving the Foaming Behavior of Polylactic Acid via Three Strategies.

Controlling foamability plays the central role in preparing PLA foams with high performances. To achieve this, chain extension was often used to improve the rheological property of PLA resins; however, despite the availability of this approach, it often deteriorates the biodegradability of PLA and greatly increases the processing cost and complexity. Hence, we reported a special crystallization induction method to design PLA foams with a tunable cellular structure and a high expansion ratio.

Bivalent antibody pliers inhibit β-tryptase by an allosteric mechanism dependent on the IgG hinge.

Human β-tryptase, a tetrameric trypsin-like serine protease, is an important mediator of allergic inflammatory responses in asthma. Antibodies generally inhibit proteases by blocking substrate access by binding to active sites or exosites or by allosteric modulation. The bivalency of IgG antibodies can increase potency via avidity, but has never been described as essential for activity.

Brain delivery of therapeutic proteins using an Fc fragment blood-brain barrier transport vehicle in mice and monkeys.

Effective delivery of protein therapeutics to the central nervous system (CNS) has been greatly restricted by the blood-brain barrier (BBB). We describe the development of a BBB transport vehicle (TV) comprising an engineered Fc fragment that exploits receptor-mediated transcytosis for CNS delivery of biotherapeutics by binding a highly expressed brain endothelial cell target. TVs were engineered using directed evolution to bind the apical domain of the human transferrin receptor (hTfR) without the use of amino acid insertions, deletions, or unnatural appendages.

Target arm affinities determine preclinical efficacy and safety of anti-HER2/CD3 bispecific antibody.

Systemic cytokine release and on-target/off-tumor toxicity to normal tissues are the main adverse effects limiting the clinical utility of T cell-redirecting therapies. This study was designed to determine how binding affinity for CD3 and tumor target HER2 impact the efficacy and nonclinical safety of anti-HER2/CD3 T cell-dependent antibodies (TDBs). Affinity was found to be a major determinant for the overall tolerability.

A Novel Zirconium Modified Arylacetylene Resin: Preparation, Thermal Properties and Ceramifiable Mechanism.

With the rapid development of thermal protection systems for the aerospace industry and power electronics, polyarylacetylene (PAA) resin plays an important role because of its good mechanical properties, high glass transition temperature (T), low water absorption, high char yield (Y), and the fact that there is no byproduct released in the curing process. In order to further improve the thermal property of PAA based FRP for the thermal protection field, the introduction of a zirconium element into arylacetylene is promising. In this paper, zirconium modified arylacetylene (ZAA) resin was prepared by two-step synthesis.

An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma.

Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active β-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment.

Total Glycosides of Peony Protects Against Inflammatory Bowel Disease by Regulating IL-23/IL-17 Axis and Th17/Treg Balance.

Inflammatory bowel disease (IBD) is a group of autoimmune diseases, including ulcerative colitis and Crohn's disease, characterized by nonspecific inflammation in the gut. Total glycoside of peony (TGP) has been widely used for treatment of autoimmune diseases because of its pharmacological effects. However, it is lack of depth in whether TGP regulate T helper 17 cell (Th17) / T regulatory cell (Treg) immune balance or interleukin 23 (IL-23) / IL-17 axis to achieve the goal of treating IBD.

Characterization of the chemical composition of white chrysanthemum flowers of Hangzhou by using high-performance ion trap mass spectrometry.

In this study, high-performance liquid chromatography coupled with amaZon SL high-performance ion trap mass spectrometry was used to analyze the target components in white chrysanthemum flowers of Hangzhou. Twenty-one components were detected and identified in both white chrysanthemum flowers of Hangzhou samples by using target compound analysis. Furthermore, seven new compounds in white chrysanthemum flowers of Hangzhou were found and identified by analyzing the fragment ion behavior in the mass spectra.

Discovery of Novel Blood-Brain Barrier Targets to Enhance Brain Uptake of Therapeutic Antibodies.

The blood-brain barrier (BBB) poses a major challenge for developing effective antibody therapies for neurological diseases. Using transcriptomic and proteomic profiling, we searched for proteins in mouse brain endothelial cells (BECs) that could potentially be exploited to transport antibodies across the BBB. Due to their limited protein abundance, neither antibodies against literature-identified targets nor BBB-enriched proteins identified by microarray facilitated significant antibody brain uptake.

Adsorption of Cd(II), Cu(II) and Ni(II) ions by cross-linking chitosan/rectorite nano-hybrid composite microspheres.

Chitosan/rectorie (CTS/REC) nano-hybrid composite microsphere was prepared by changing the proportion of CTS/REC with 2:1, 3:1 and 4:1. Compared with the pure cross-linking chitosan microsphere, the nano-hybrid composite microsphere was proved to have better sorption capacity of Cd(II), Cu(II) and Ni(II), especially 2:1(CTS/REC-1). The adsorption behavior of the microsphere of Cd(II), Cu(II) and Ni(II) was investigated in single and binary metal systems.

Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies.

Bispecific antibodies and antibody fragments in various formats have been explored as a means to recruit cytolytic T cells to kill tumor cells. Encouraging clinical data have been reported with molecules such as the anti-CD19/CD3 bispecific T cell engager (BiTE) blinatumomab. However, the clinical use of many reported T cell-recruiting bispecific modalities is limited by liabilities including unfavorable pharmacokinetics, potential immunogenicity, and manufacturing challenges.

Quantitative analysis coupled with toxic evaluation to investigate the influence of sulfur-fumigation on the quality of Chrysanthemum morifolium.

In the present study, quantitative analysis coupled with toxic evaluation was applied to investigate the influence of sulfur-fumigation on the quality of Chrysanthemum morifolium. The results showed that the average contents of six flavonoids (cynaroside, hyperoside, isoquercitrin, luteolin, apigenin, and diosmetin) in sulfur-fumigated C. morifolium samples decreased by about 6.

[Sedum sarmentosun bunge extraction ameliorated severe acute pancreatitis-induced lung injury: an experimental research]].

Objective: To explore the effect of Sedum sarmentosum Bunge Extract (SSBE) on severe acute pancreatitis (SAP) induced acute lung injury (ALI) model rats and their excessive inflammatory reactions.

Methods: Forty-two healthy adult male Sprague-Dawley (SD) rats were randomly divided into 3 groups, the sham-operated control group (C), the SAP group (SAP), and the SSBE treated group (SSBE), 14 in each group. SAP induced ALl rat model was induced by retrograde injection of 5% sodium taurocholate (1 mL/kg) into the pancreatic duct.

A new species of the genus Triplophysa (Nemacheilinae), Triplophysa qilianensis sp. nov, from Qinghai, China.

A new nemacheilid loach species, Triplophysa qilianensis, is described from Heihe River in Haibei Tibetan Autonomous Prefecture, Qinghai, China. It can be distinguished from all other species of Triplophysa by the following combination of characters: body long and compressed; skin smooth, scaleless; head short (20.1-23.

Inhibition of spontaneous canine benign prostatic hyperplasia by an Urtica fissa polysaccharide fraction.

In this study, we investigated the inhibition of spontaneous canine benign prostatic hyperplasia by a crude polysaccharide fraction extracted from Urtica fissa roots and stems. After oral administration of U. fissa polysaccharide fraction for 3 months, the dog prostatic volume reduced significantly when compared to that before treatment using CT examination.

Ultra-performance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry analysis of the impact of bran-processing on the chemical profile of Radix Paeoniae Alba (Baishao).

In this study, a rapid and versatile ultra-performance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry-based chemical profiling approach was applied to evaluate chemical constitution of crude and processed Radix Paeoniae Alba (RPA) samples. A total of 44 compounds were identified, among which the contents of 9 compounds in processed samples were obviously decreased and 8 compounds were increased. Furthermore, compound 28 was not found in RPA sample after stir-frying with wheat bran.

Rapid identif ication and comparative analysis of chemical constituents in herbal medicine Fufang decoction by ultra-high-pressure liquid chromatography coupled with a hybrid linear ion trap-high-resolution mass spectrometry.

This study was conducted to reveal the relation between herbal medicine Fufang decoction and a single drug in terms of material base. Da-Cheng-Qi decoction (DCQD) was used as a model. Ultrahigh-pressure liquid chromatography coupled with a hybrid linear ion trap-high-resolution mass spectrometry (UHPLC-LTQ-Orbitrap) was applied to detect and identify the main chemical compounds.

Static headspace-multicapillary column with gas chromatography coupled to ion mobility spectrometry as a simple approach for the discrimination of crude and processed traditional Chinese medicines.

The processing procedure can alter the nature and chemical transformation of traditional Chinese medicine to accommodate different clinical dispensing and preparation requirements. In this study, static headspace-multicapillary column with gas chromatography coupled to ion mobility spectrometry was developed for the rapid and sensitive discrimination of crude and processed traditional Chinese medicine. Using Radix Paeoniae Alba as a traditional Chinese medicine model, the combined power of this approach was illustrated by classifying the crude and processed Radix Paeoniae Alba samples into two main categories.