Proteome-Wide Mendelian Randomization Analysis to Identify Potential Plasma Biomarkers and Therapeutic Targets for Epithelial Ovarian Cancer Subtypes.

Background: Epithelial ovarian cancer (EOC) remains an unmet medical challenge due to its insidious onset, atypical symptoms, and increasing resistance to conventional chemotherapeutic agents. It is imperative to explore novel biomarkers and generate innovative target drugs.

Methods: To identify potential proteins with causal association to EOC subtypes, we conducted a Mendelian Randomization (MR) analysis using 15,419 protein quantitative trait loci (pQTLs) associated with 2015 proteins.

GSK3β-driven SOX2 overexpression is a targetable vulnerability in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest forms of human malignancy that currently lacks approved targeted therapeutics. Accumulating evidence suggests that SOX2 overexpression is a key driving factor for ESCC and various squamous cell carcinoma. Here, through screening a small-molecule kinase inhibitor library, we identified GSK3β as a kinase that is critically required for robust SOX2 expression in ESCC cells.

LincRNA-p21 Upregulates Nuclear Orphan Receptor Nr4a2 and Aggravates Myocardial Ischemia/Reperfusion Injury via Targeting MiR-466i-5p.

Myocardial ischemia/reperfusion (I/R) injury can bring about more cardiomyocyte death and aggravate cardiac dysfunction, but its pathogenesis remains unclear. This study aimed to investigate the role of long intergenic noncoding RNA-p21 (LincRNA-p21) in myocardial I/R injury and its underlying mechanism. Mice were subjected to myocardial I/R injury by ligation and release of the left anterior descending artery, and HL-1 cardiomyocytes were treated with hydrogen peroxide.

The low fetal fraction at the first trimester is associated with adverse pregnancy outcomes in IVF singleton pregnancies with single embryo transfer from frozen cycles.

Purpose: To study the associations between fetal fraction at the first trimester and subsequent adverse pregnancy outcomes (APOs) in IVF singleton pregnancies with single embryo transfer from frozen cycles.

Methods: This is a single-center retrospective cohort study on IVF singleton pregnancies with single embryo transfer from frozen cycles. A total of 8457 women were collected between March 2015 and September 2018 from the Center for Reproductive Medicine, Shandong University, China.

Aldehyde dehydrogenase 2 protects against acute kidney injury by regulating autophagy via the Beclin-1 pathway.

The mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) catalyzes the detoxification of acetaldehyde and endogenous lipid aldehydes. Approximately 40% of East Asians, accounting for 8% of the human population, carry the E504K mutation in ALDH2 that leads to accumulation of toxic reactive aldehydes and increases the risk for cardiovascular disease, cancer, and Alzheimer disease, among others. However, the role of ALDH2 in acute kidney injury (AKI) remains poorly defined and is therefore the subject of the present study using various cellular and organismal sources.

Analysis of potential factors contributing to refusal of invasive strategy after ST-segment elevation myocardial infarction in China.

Background: Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China.

Methods: We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China.

Inhibition of adenosine kinase attenuates myocardial ischaemia/reperfusion injury.

Increased adenosine helps limit infarct size in ischaemia/reperfusion-injured hearts. In cardiomyocytes, 90% of adenosine is catalysed by adenosine kinase (ADK) and ADK inhibition leads to higher concentrations of both intracellular adenosine and extracellular adenosine. However, the role of ADK inhibition in myocardial ischaemia/reperfusion (I/R) injury remains less obvious.

Aldehyde dehydrogenase 2 preserves mitochondrial morphology and attenuates hypoxia/reoxygenation-induced cardiomyocyte injury.

Background: Disturbance of mitochondrial fission and fusion (termed mitochondrial dynamics) is one of the leading causes of ischemia/reperfusion (I/R)-induced myocardial injury. Previous studies showed that mitochondrial aldehyde dehydrogenase 2 (ALDH2) conferred cardioprotective effect against myocardial I/R injury and suppressed I/R-induced excessive mitophagy in cardiomyocytes. However, whether ALDH2 participates in the regulation of mitochondrial dynamics during myocardial I/R injury remains unknown.

Applications of noninvasive prenatal testing in vanishing twin syndrome pregnancies after treatment of assisted reproductive technology in a single center.

Objective: The objective of the study is to assess the clinical application of noninvasive prenatal testing (NIPT) for VTS pregnancies after the treatment of assisted reproductive technology (ART).

Method: This was a retrospective study on VTS pregnancies through ART treatment. Participants underwent NIPT at 11 to 13 weeks gestation by sequencing.

Differentially expressed lncRNAs, miRNAs and mRNAs with associated ceRNA networks in a mouse model of myocardial ischemia/reperfusion injury.

Non‑coding RNAs, including long non‑coding RNAs (lncRNAs) and microRNAs (miRNAs/miRs), have significant regulatory effects on a number of biological processes in myocardial ischemia/reperfusion (I/R) injury, including cell differentiation, proliferation and apoptosis. In the present study, the expression levels of lncRNAs, miRNAs and mRNAs were evaluated in a mouse model of myocardial I/R injury. The potential functions of these differentially expressed genes were then analyzed via Gene Ontology and pathway analyses.

Aldehyde Dehydrogenase 2 Protects Against Post-Cardiac Arrest Myocardial Dysfunction Through a Novel Mechanism of Suppressing Mitochondrial Reactive Oxygen Species Production.

Post-cardiac arrest myocardial dysfunction significantly contributes to early mortality after the return of spontaneous circulation. However, no effective therapy is available now. Aldehyde dehydrogenase 2 (ALDH2) enzyme has been shown to protect the heart from aldehyde toxicity such as 4-hydroxy-2-nonenal (4-HNE) and oxidative stress.

ALDH2 Activation Inhibited Cardiac Fibroblast-to-Myofibroblast Transformation Via the TGF-β1/Smad Signaling Pathway.

Pathological stimulus-triggered differentiation of cardiac fibroblasts plays a major role in the development of myocardial fibrosis. Aldehyde dehydrogenase 2 (ALDH2) was reported to exert a protective role in cardiovascular disease, and whether ALDH2 is involved in cardiac fibroblast differentiation remains unclear. In this study, we used transforming growth factor-β1 (TGF-β1) to induce the differentiation of human cardiac fibroblasts (HCFs) and adopted ALDH2 activator Alda-1 to verify the influence of ALDH2 on HCF differentiation.

ALDH2 protects against alcoholic cardiomyopathy through a mechanism involving the p38 MAPK/CREB pathway and local renin-angiotensin system inhibition in cardiomyocytes.

Background: Angiotensin II (Ang II) in the local cardiac renin-angiotensin system (RAS) is closely associated with alcoholic cardiomyopathy (ACM). Inhibition of local cardiac RAS has great significance in the treatment of ACM. Although aldehyde dehydrogenase 2 (ALDH2) has been demonstrated to protect against ACM through detoxification of aldehydes, the precise mechanisms are largely unknown.

Inhibition of ALDH2 by O-GlcNAcylation contributes to the hyperglycemic exacerbation of myocardial ischemia/reperfusion injury.

Although hyperglycemia is causally related to adverse outcomes after myocardial ischemia/reperfusion (I/R), the underlying mechanisms are largely unknown. Here, we investigated whether excessive O-linked-N-acetylglucosamine (O-GlcNAc) modification of acetaldehyde dehydrogenase 2 (ALDH2), an important cardioprotective enzyme, was a mechanism for the hyperglycemic exacerbation of myocardial I/R injury. Both acute hyperglycemia (AHG) and diabetes (DM)-induced chronic hyperglycemia increased cardiac dysfunction, infarct size and apoptosis index compared with normal saline (NS)+I/R rats (P<0.

Donor substrate promiscuity of bacterial β1-3-N-acetylglucosaminyltransferases and acceptor substrate flexibility of β1-4-galactosyltransferases.

β1-3-N-Acetylglucosaminyltransferases (β3GlcNAcTs) and β1-4-galactosyltransferases (β4GalTs) have been broadly used in enzymatic synthesis of N-acetyllactosamine (LacNAc)-containing oligosaccharides and glycoconjugates including poly-LacNAc, and lacto-N-neotetraose (LNnT) found in the milk of human and other mammals. In order to explore oligosaccharides and derivatives that can be synthesized by the combination of β3GlcNAcTs and β4GalTs, donor substrate specificity studies of two bacterial β3GlcNAcTs from Helicobacter pylori (Hpβ3GlcNAcT) and Neisseria meningitidis (NmLgtA), respectively, using a library of 39 sugar nucleotides were carried out. The two β3GlcNAcTs have complementary donor substrate promiscuity and 13 different trisaccharides were produced.

ALDH2---The Genetic Polymorphism and Enzymatic Activity Regulation: Their Epidemiologic and Clinical Implications.

Background: The human aldehyde dehydrogenase 2 (ALDH2) is the most effective enzyme in the detoxification of alcohol metabolite acetaldehyde. The ALDH2*2 mutation is caused by a single nucleotide substitution which results in a nearly inactive form of ALDH2 enzyme. The ALDH2 genotype has been used as a surrogate of alcohol to get causal inferences of alcohol in related diseases implementing Mendelian randomization approach.

Sequential one-pot multienzyme (OPME) synthesis of lacto-N-neotetraose and its sialyl and fucosyl derivatives.

Lacto-N-neotetraose and its sialyl and fucosyl derivatives including Lewis x (Le(x)) pentasaccharide, sialyl Lewis x (sLe(x)) hexasaccharide and internally sialylated derivatives were enzymatically synthesized from readily available lactoside, commercially available uridine 5'-diphosphate-glucose (UDP-Glc) and the corresponding monosaccharides using a highly efficient sequential one-pot multienzyme (OPME) strategy. The OPME strategy which combines bacterial glycosyltransferases and sugar nucleotide generation enzymes provides easy access to the biologically important complex oligosaccharides at preparative scale. Moreover, the same OPME strategy can be used for the regioselective introduction of sialic acid to the internal galactose unit of LNnT in a designed glycosylation route by simply changing the glycosylation sequence.

Improved one-pot multienzyme (OPME) systems for synthesizing UDP-uronic acids and glucuronides.

Arabidopsis thaliana glucuronokinase (AtGlcAK) was cloned and shown to be able to use various uronic acids as substrates to produce the corresponding uronic acid-1-phosphates. AtGlcAK or Bifidobacterium infantis galactokinase (BiGalK) was used with a UDP-sugar pyrophosphorylase, an inorganic pyrophosphatase, with or without a glycosyltransferase for highly efficient synthesis of UDP-uronic acids and glucuronides. These improved cost-effective one-pot multienzyme (OPME) systems avoid the use of nicotinamide adenine dinucleotide (NAD(+))-cofactor in dehydrogenase-dependent UDP-glucuronic acid production processes and can be broadly applied for synthesizing various glucuronic acid-containing molecules.

Synthetic disialyl hexasaccharides protect neonatal rats from necrotizing enterocolitis.

Two novel synthetic α2-6-linked disialyl hexasaccharides, disialyllacto-N-neotetraose (DSLNnT) and α2-6-linked disialyllacto-N-tetraose (DS'LNT), were readily obtained by highly efficient one-pot multienzyme (OPME) reactions. The sequential OPME systems described herein allowed the use of an inexpensive disaccharide and simple monosaccharides to synthesize the desired complex oligosaccharides with high efficiency and selectivity. DSLNnT and DS'LNT were shown to protect neonatal rats from necrotizing enterocolitis (NEC) and are good therapeutic candidates for preclinical experiments and clinical application in treating NEC in preterm infants.

A one-pot approach to bio-synthesize globotriose and its derivatives from simpler substrates.

Globotriose is involved in numerous pathogenic processes and drug development strategies. Recent studies have demonstrated that globotriosylceramide could be used in colon cancer therapy and as a crucial indicator for susceptibility to HIV-1 infection. Therefore, the cost-effective and facile approaches for large-scale production of globotiose as potential drugs are highly required.