Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.

PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin () is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying.

Scutellarin inhibits inflammatory PANoptosis by diminishing mitochondrial ROS generation and blocking PANoptosome formation.

PANoptosis is manifested with simultaneous activation of biomarkers for both pyroptotic, apoptotic and necroptotic signaling via the molecular platform PANoptosome and it is involved in pathologies of various inflammatory diseases including hemophagocytic lymphohistiocytosis (HLH). Scutellarin is a flavonoid isolated from herbal Erigeron breviscapus (Vant.) Hand.

Inflammatory cell death PANoptosis is induced by the anti-cancer curaxin CBL0137 via eliciting the assembly of ZBP1-associated PANoptosome.

Objective: PANoptosis, a new form of regulated cell death, concomitantly manifests hallmarks for pyroptosis, apoptosis, and necroptosis. It has been usually observed in macrophages, a class of widely distributed innate immune cells in various tissues, upon pathogenic infections. The second-generation curaxin, CBL0137, can trigger necroptosis and apoptosis in cancer-associated fibroblasts.

Triptolide induces PANoptosis in macrophages and causes organ injury in mice.

Macrophages represent the first lines of innate defense against pathogenic infections and are poised to undergo multiple forms of regulated cell death (RCD) upon infections or toxic stimuli, leading to multiple organ injury. Triptolide, an active compound isolated from Tripterygium wilfordii Hook F., possesses various pharmacological activities including anti-tumor and anti-inflammatory effects, but its applications have been hampered by toxic adverse effects.

Theaflavin mitigates acute gouty peritonitis and septic organ injury in mice by suppressing NLRP3 inflammasome assembly.

Activation of NLR family pyrin domain-containing 3 (NLRP3) inflammasome plays important role in defending against infections, but its aberrant activation is causally linked to many inflammatory diseases, thus being a therapeutic target for these diseases. Theaflavin, one major ingredient of black tea, exhibits potent anti-inflammatory and anti-oxidative activities. In this study, we investigated the therapeutic effects of theaflavin against NLRP3 inflammasome activation in macrophages in vitro and in animal models of related diseases.

Celastrol inhibits necroptosis by attenuating the RIPK1/RIPK3/MLKL pathway and confers protection against acute pancreatitis in mice.

Necroptosis is a necrotic form of regulated cell death, which is primarily mediated by the receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) pathway in a caspase-independent manner. Necroptosis has been found to occur in virtually all tissues and diseases evaluated, including pancreatitis. Celastrol, a pentacyclic triterpene extracted from the roots of Tripterygium wilfordii (thunder god vine), possesses potent anti-inflammatory and anti-oxidative activities.

Dimethyl fumarate inhibits necroptosis and alleviates systemic inflammatory response syndrome by blocking the RIPK1-RIPK3-MLKL axis.

Necroptosis has been implicated in various inflammatory diseases including tumor-necrosis factor-α (TNF-α)-induced systemic inflammatory response syndrome (SIRS). Dimethyl fumarate (DMF), a first-line drug for treating relapsing-remitting multiple sclerosis (RRMS), has been shown to be effective against various inflammatory diseases. However, it is still unclear whether DMF can inhibit necroptosis and confer protection against SIRS.

Replication of previous genome-wide association studies of and SNPs in a gestational diabetes mellitus case-control sample from Han Chinese population.

Four novel glucose metabolism risk loci (1 rs4746822, rs6517656, rs13342232 and rs998451) were identified in recent genome-wide association studies (GWAS) of Afro-Caribbean, European, Hispanic, Thai, Mexican, Latin American and Indian populations. None of the abovementioned SNPs has been reported in a Han Chinese population. To replicate the relationships between 1 rs4746822, rs6517656, rs13342232 and rs998451 with gestational diabetes mellitus (GDM) in a Han Chinese population.

PRPS1 silencing reverses cisplatin resistance in human breast cancer cells.

PRPS1 (phosphoribosyl pyrophosphate synthetase 1), which drives the nucleotide biosynthesis pathway, modulates a variety of functions by providing central building blocks and cofactors for cell homeostasis. As tumor cells often display abnormal nucleotide metabolism, dysregulated de-novo nucleotide synthesis has potential impacts in cancers. We now report that PRPS1 is specifically and highly expressed in chemoresistant (CR) cancer cells derived from cisplatin-resistant human breast cancer cell lines SK-BR-3 and MCF-7.

Epigallocatechin Gallate Extends Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment for Brain Ischemic Stroke: A Randomized Double-Blind and Placebo-Controlled Trial.

Objectives: Recombinant tissue plasminogen activator (rt-PA) is a safe and effective treatment for acute brain ischemia stroke, albeit with a narrow therapeutic window. We aimed to assess the effect of epigallocatechin gallate (EGCG) in extending the rt-PA treatment window in this clinical trial among stroke patients.

Methods: Patients were randomly assigned according to their onset-to-treatment time (OTT) and were then treated with rt-PA simultaneously with EGCG or placebo.

Worldwide prevalence of adverse pregnancy outcomes among singleton pregnancies after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis.

Purpose: The worldwide prevalence of adverse pregnancy outcomes (APOs) in singleton pregnancies after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is suggested to vary; however, a complete overview is missing. The aim of this review is to estimate the worldwide prevalence of APOs associated with IVF/ICSI singleton pregnancies.

Methods: PubMed, Google Scholar, Cochrane Libraries, and Chinese databases were searched for studies assessing APOs among IVF/ICSI singleton births through March 2016.

Epigallocatechin Gallate Extends the Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment in Ischemic Rats.

Background: Ischemic stroke is the leading cause of death and disability worldwide. To date, recombinant tissue plasminogen activator (rt-PA) remains the only safe and effective pharmaceutical treatment for brain ischemia, but delayed rt-PA administration leads to hyperperfusion, which severely limits its clinical efficacy.

Methods: In this study, we investigated the effect of epigallocatechin gallate (EGCG) in extending the therapeutic window of rt-PA using a rat middle cerebral artery occlusion (MCAO) model.