A Phase I, Double-Blind, Placebo-Controlled, Randomized, Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Food Effect and Potential Efficacy of PS1 in Subjects

This is a phase I, double-blind, placebo-controlled, randomized, single- and multiple-ascending dose study to evaluate new study intervention, PS1. PS1 is a potential blood glucose control medication, which is developed by Pharmasaga Co. Ltd. planned for treating type II diabetes mellitus (T2DM). This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), food effect and potential efficacy of PS1 in subjects.

Start Date22 Dec 2023

Sponsor / Collaborator

Pharmasaga Co. Ltd.

100 Clinical Results associated with PDIA4

100 Translational Medicine associated with PDIA4

0 Patents (Medical) associated with PDIA4

247

Literatures (Medical) associated with PDIA4

01 Dec 2024·Applied Microbiology and Biotechnology

Quantitative proteomics reveals cellular responses to individual mAb expression and tunicamycin in CHO cells

Article

Author: Kunert, Renate ; Marzban, Gorji ; Schwaigerlehner, Linda ; Sandell, Felix L ; Sulaj, Eldi ; Dohm, Juliane C

AbstractChinese hamster ovary (CHO) cells are popular in the pharmaceutical industry for their ability to produce high concentrations of antibodies and their resemblance to human cells in terms of protein glycosylation patterns. Current data indicate the relevance of CHO cells in the biopharmaceutical industry, with a high number of product commendations and a significant market share for monoclonal antibodies. To enhance the production capabilities of CHO cells, a deep understanding of their cellular and molecular composition is crucial. Genome sequencing and proteomic analysis have provided valuable insights into the impact of the bioprocessing conditions, productivity, and product quality. In our investigation, we conducted a comparative analysis of proteomic profiles in high and low monoclonal antibody–producing cell lines and studied the impact of tunicamycin (TM)-induced endoplasmic reticulum (ER) stress. We examined the expression levels of different proteins including unfolded protein response (UPR) target genes by using label-free quantification techniques for protein abundance. Our results show the upregulation of proteins associated with protein folding mechanisms in low producer vs. high producer cell line suggesting a form of ER stress related to specific protein production. Further, Hspa9 and Dnaja3 are notable candidates activated by the mitochondria UPR and play important roles in protein folding processes in mitochondria. We identified significant upregulation of Nedd8 and Lgmn proteins in similar levels which may contribute to UPR stress. Interestingly, the downregulation of Hspa5/Bip and Pdia4 in response to tunicamycin treatment suggests a low-level UPR activation.Key points• Proteome profiling of recombinant CHO cells under mild TM treatment.• Identified protein clusters are associated with the unfolded protein response (UPR).• The compared cell lines revealed noticeable disparities in protein expression levels.

01 Dec 2024·International Immunopharmacology

Protein disulfide isomerase A4 binds to Brucella BtpB and mediates intracellular NAD+/NADH metabolism in RAW264.7 cells

Article

Author: Liu, Wei ; Zhou, Dong ; Hao, Mingyue ; Wang, Minghui ; Li, Junmei ; Zhai, Yunyi ; Liu, Xiaofang ; Jin, Yaping ; Yuan, Ningqiu ; Wang, Aihua

The Toll/interleukin-1 receptor (TIR) signaling domain is distributed widely in mammalian Toll-like receptors and adaptors, plant nucleotide-binding leucine-rich repeat receptors, and specific bacterial virulence proteins. Proteins that possess TIR domain exhibit NADase activity which is distinct from the canonical signaling function of these domains. However, the effects of bacterial TIR domain proteins on host metabolic switches and the underlying mechanism of NADase activity in these proteins remain unclear. Here, we utilized Brucella TIR domain-containing type IV secretion system effector protein, BtpB, to explore the mechanism of NADase activity in host cells. We showed that using ectopic expression BtpB not only generates depletion of NAD⁺ but also loss of NADH and ATP in RAW264.7 macrophage cells. Moreover, immunoprecipitation-mass spectrometry, co-immunoprecipitation, and confocal microscope assays revealed that BtpB interacted with host protein disulfide isomerase A4 (PDIA4). The Brucella mutant strain deleted the gene for BtpB, significantly decreased PDIA4 expression. Furthermore, our data revealed that PDIA4 played an important role in regulating intracellular NAD⁺/NADH levels in macrophages, and PDIA4 overexpression restored the decline of intracellular NAD⁺ and NADH levels induced by Brucella BtpB. The results provide new insights into the metabolic regulatory activity of TIR domain proteins in the critical human and animal pathogen Brucella.

01 Nov 2024·Aquatic Toxicology

A transcriptomics-based analysis of mechanisms involved in the neurobehavioral effects of 6PPD-quinone on early life stages of zebrafish

Article

Author: Chen, Kun ; Wu, Xiangyang ; Shi, Yanhong ; Zhang, Yibing ; Li, Ming ; Tang, Jie ; Qiu, Xuchun

As an emerging pollutant frequently detected in aquatic ecosystems, the toxicity of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-quinone) on fish has been confirmed, but insight into the mechanisms underlying those adverse effects is still limited. Thus, we exposed zebrafish embryos to 6PPD-quinone at 0, 0.25, 2.5, and 25 μg/L until 120 h post-fertilization (hpf), and investigated the variations in their development, behavior, monoamine neurotransmitter levels, and transcriptional profile. Exposure to 6PPD-quinone notably elevated the heart rate of zebrafish at 48 hpf (at 2.5 and 25 μg/L) and 72 hpf (at 0.25, 2.5, and 25 μg/L). In the dark-light transition test, the locomotor activity of zebrafish larvae exposed to 6PPD-quinone significantly increased, especially in the dark periods. Exposure to 6PPD-quinone also altered the dopamine level and its turnover in zebrafish, which exhibited significant correlations to their locomotor activity. RNA sequencing identified 394 differentially expressed genes (DEGs), most of which have the molecular function of binding and catalytic activity. Five DEGs were predicted as the key driver genes in the protein-protein interaction networks associated with circadian rhythm (i.e., npas2), protein processing in endoplasmic reticulum (i.e., hsp90b1 and pdia4), and estrogen signaling pathway (i.e., hsp90aa1.1 and hsp90aa1.2). Our findings provide more insights into mechanisms underlying the toxicity of 6PPD-quinone to teleosts and highlight the necessity to assess its potential risks to aquatic ecosystems.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

PDIA4

Basic Info

Related

Analysis