Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach.

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys.

Bavachin induces liver injury and cell apoptosis by targeting Wnt/β-catenin/DRP1 signaling pathway mediated mitochondrial dysfunction.

Psraleae Fructus (PF) is a well-known traditional Chinese medicine in China. While numerous liver injury reports caused by PF limits its clinical application. Bavachin, a flavonoid compound isolated from the fruits of Psoralea corylifolia L.

A multi-functional hypoxia/esterase dual stimulus responsive and hyaluronic acid-based nanomicelle for targeting delivery of chloroethylnitrosouea.

Carmustine (BCNU), a vital type of chloroethylnitrosourea (CENU), inhibits tumor cells growth by inducing DNA damage at O position of guanine and eventually forming dG-dC interstrand cross-links (ICLs). However, the clinical application of BCNU is hindered to some extent by the absence of tumor selectivity, poor stability and O-alkylguanine-DNA alkyltransferase (AGT) mediated drug resistance. In recent years, tumor microenvironment has been widely utilized for advanced drug delivery.

Inflammation and coagulation abnormalities via the activation of the HMGB1‑RAGE/NF‑κB and F2/Rho pathways in lung injury induced by acute hypoxia.

High‑altitude acute hypoxia is commonly associated with respiratory cardiovascular diseases. The inability to adapt to acute hypoxia may lead to cardiovascular dysfunction, lung injury and even death. Therefore, understanding the molecular basis of the adaptation to high‑altitude acute hypoxia may reveal novel therapeutic approaches with which to counteract the detrimental consequences of hypoxia.

Mechanisms and Molecular Targets of Compound Danshen Dropping Pill for Heart Disease Caused by High Altitude Based on Network Pharmacology and Molecular Docking.

Compound Danshen dropping pill (CDDP), a famous Chinese medicine formula, has been widely used to treat high-altitude heart disease in China. However, its molecular mechanisms, potential targets, and bioactive ingredients remain elusive. In this study, network pharmacology, molecular docking, and validation experiments were combined to investigate the effective active ingredients and molecular mechanisms of CDDP in the treatment of high-altitude heart disease.

Ophiopogonin D Increases SERCA2a Interaction with Phospholamban by Promoting CYP2J3 Upregulation.

Ophiopogonin D (OPD), a compound from the Chinese herb Radix Ophiopogonis, reportedly induces increased levels of cytochrome P450 2J3 (CYP2J3)/epoxyeicosatrienoic acids (EETs) and Ca in rat cardiomyocytes. Little is known regarding the specific mechanism between CYP2J3 and Ca homeostasis. Here, we investigated whether CYP2J3 is involved in the protective action of OPD on the myocardium by activating the Ca homeostasis-related protein complex (SERCA2a and PLB) in H9c2 rat cardiomyoblast cells.

Sestrin2 protects against bavachin induced ER stress through AMPK/mTORC1 signaling pathway in HepG2 cells.

Bavachin (BV), a natural flavonoid compound derived from Psoralea corylifolia L, has been reported to be a potential hepatotoxin. Our previous studies have found that BV can induce endoplasmic reticulum (ER) stress-related cell apoptosis, but the molecular mechanism underlying BV-induced ER stress remains obscure. Sestrin2, a highly conserved stress-inducible protein, is involved in the cellular responses of various stress conditions and homeostatic regulation.

[Ophiopogonin D protects cardiomyocytes against ophiopogonin D'-induced injury through suppressing endoplasmic reticulum stress].

This study is aimed to investigate the intervention effect and possible mechanism of ophiopogonin D( OPD) in protecting cardiomyocytes against ophiopogonin D'( OPD')-induced injury,and provide reference for further research on toxicity difference of saponins from ophiopogonins. CCK-8 assay was used to evaluate the effect of OPD and OPD' on cell viability. The effect of OPD on OPD'-induced cell apoptosis was measured by flow cytometry.

TMEM88 mediates inflammatory cytokines secretion by regulating JNK/P38 and canonical Wnt/β-catenin signaling pathway in LX-2 cells.

Recent data have shown that Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane, interacts with the PDZ domain of disheveled-1 (Dvl-1) in Xenopus embryos. Indeed, TMEM88 might inhibit the canonical Wnt/β-catenin signaling pathway by competing with LRP5/6 for interaction with Dvl-1. TMEM88 plays a crucial role in regulating human stem cell differentiation and embryonic development.

Progress and prospects of circular RNAs in Hepatocellular carcinoma: Novel insights into their function.

Hepatocellular carcinoma (HCC) is one of the most predominant subjects of liver malignancies, which arouses global concern in the recent years. Advanced studies have found that Circular RNAs (circRNAs) are differentially expressed in HCC, with its regulatory capacity in HCC pathogenesis and metastasis. However, the underlying mechanism remains largely unknown.

New advances of TMEM88 in cancer initiation and progression, with special emphasis on Wnt signaling pathway.

Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane. Recent studies showed that TMEM88 was involved in the regulation of several types of cancer. TMEM88 was expressed at significantly higher levels in breast cancer (BC) cell line than in normal breast cell line with co-localized with Dishevelled (DVL) in the cytoplasm of BC cell line.

Therapeutic potential of cysteine-rich protein 61 in rheumatoid arthritis.

Cysteine-rich protein 61 (Cyr61)/CCN1, a product of an immediate early gene, can directly accommodate cell adhesion and migratory processes whilst simultaneously regulating the production of other cytokines and chemokines through paracrine and autocrine feedback loops. This intricate functionality of Cyr61 indicate its important role in targeting components of the infectious or chronic inflammatory disease processes including rheumatoid arthritis (RA). Recent work has focused on the role of Cyr61 in RA.