Isoglutaminyl Cyclase Overexpression Enhances KYSE30 Cancer Cell Proliferation and Migration via the MAPK Signaling Pathway.

To understand how upregulated isoglutaminyl cyclase (isoQC) is involved in the initiation of diseases such as cancer, we developed a human KYSE30 carcinoma cell model in which isoQC was stably overexpressed. GO and KEGG analysis of the DEGs (228) and DEPs (254) respectively implicated isoQC on the proliferation invasion and metastasis of cells and suggested that isoQC might participate in the regulation of MAPK, RAS, circadian rhythm, and related pathways. At the functional level, isoQC-overexpressing KYSE30 cells showed enhanced proliferation, migration, and invasion capacity. Next, we decided to study the precise effect of isoQC overexpression on JNK, p-JNK, AKT, p-AKT, ERK, p-ERK, and PER2, as RNA levels of these proteins are significantly correlated with signal levels indicated in RNA-Seq analysis, and these candidates are the top correlated DEPs enriched in RT-qPCR analysis. We saw that only p-ERK expression was inhibited, while PER2 was increased. These phenotypes were inhibited upon exposure to PER2 inhibitor KL044, which allowed for the restoration of p-ERK levels. These data support upregulated isoQC being able to promote cancer cell proliferation and migration in vitro, likely by helping to regulate the MAPK and RAS signaling pathways, and the circadian protein PER2 might be a potential mediator.

Chitosan-based oral nanoparticles as an efficient platform for kidney-targeted drug delivery in the treatment of renal fibrosis.

There is increasingly keen interest in developing orally delivered targeted drugs, especially for diseases that require long-term medication. Hence, we manufactured nanoparticles derived from methoxypolyethylene glycol-chitosan (PCS) to enhance the oral delivery and kidney-targeted distribution of salvianolic acid B (SalB), a naturally occurring renoprotective and anti-fibrotic compound, as a model drug for the treatment of renal fibrosis. Orally administered SalB-loaded PCS nanoparticles (SalB-PCS-NPs) maintained good stability in the gastrointestinal environment, improved mucus-penetrating capacity, and enhanced transmembrane transport through a Caco-2 cell monolayer. The relative oral bioavailability of SalB-PCS-NPs to free SalB and SalB-loaded chitosan nanoparticles (SalB-CS-NPs) was 367.0 % and 206.2 %, respectively. The structural integrity of SalB-PCS-NPs after crossing the intestinal barrier was also validated by Förster resonance energy transfer (FRET) in vitro and in vivo. Fluorescein isothiocyanate (FITC)-labeled SalB-PCS-NPs showed higher kidney accumulation than free FITC and FITC-labeled SalB-CS-NPs (4.6-fold and 2.1-fold, respectively). Significant improvements in kidney function, extracellular matrix accumulation, and pathological changes were observed in a unilateral ureter obstruction mouse model of renal fibrosis after once daily oral treatment with SalB-PCS-NPs for 14 days. Thus, oral administration of SalB-PCS-NPs represents a promising new strategy for kidney-targeted drug delivery.

Development of lactoferrin-coated multifunctional copolymer micelles to cross the blood-brain barrier.

The blood-brain barrier (BBB) prevents pathogens and toxins in the bloodstream from reaching the brain, but also inhibits the delivery of agents intended to treat central nervous system disorders, such as Alzheimer's disease (AD). In this study, we prepared and evaluated a novel nano-delivery vehicle system composed of lactoferrin-conjugated (Lf-PIC@Se) micelles. We used a COOH-PEG-PAsp-PV@Se synthesis-based method to prepare the micelles, which involved self-assembly followed by EDC-NHS coupling. Using glutaminyl cyclase inhibitor 8 as a model encapsulated chemical, Lf-PIC@Se micelles achieved a good loading capacity. In vitro analysis demonstrated that Lf-PIC@Se/8 micelles were stable in both neutral and acidic pH solutions in the presence or absence of H2O2, and confirmed their biosafety and compatibility in PC12 and bEND.3 cells. Notably, the cell uptake of Lf-PIC@Se/C6 micelles was much higher than that of PIC@Se micelles, and occurred through LfR-mediated endocytosis. The presence of Se meant that Lf-PIC@Se micelles acted as ROS scavengers in PC12 cells under H2O2-induced oxidative stress, which inhibited oxidative damage and increased mitochondrial membrane potential. Hemolysis assays further demonstrated that Lf-PIC@Se represent a biocompatible carrier. Finally, in vivo experiments in mice suggested that Lf-PIC@Se micelles successfully crossed the BBB, confirming their potential as vehicles for drug delivery when treating AD and other central nervous system disorders.

Discovery of potential scaffolds for glutaminyl cyclase inhibitors: Virtual screening, synthesis, and evaluation.

Glutaminyl cyclase (QC) plays a crucial role in the early stages of Alzheimer's disease (AD), thus inhibition of QC may be a promising strategy for the treatment of early AD. Therefore, QC inhibitors with novel chemical scaffolds may contribute to the development of additional anti-AD agents. We conducted a virtual screening of 3 million compounds from the Chemdiv and Enamine databases, to discover potential scaffolds for QC inhibitors. Three scaffolds, 120974, 147706, and 141449, were selected from this structure-based virtual screening through a combination of pharmacophore modeling, a receptor-ligand pharmacophore model, and the GALAHAD model, and furtherly filtered by chelation with zinc ion and docking properties. Consequently, three compounds, 1, 2, and 3, were designed and synthesized based on these three scaffolds, respectively. The IC50 of compounds 1 and 3 against QC were 14.19 ± 4.21 and 4.34 ± 0.35 µM, respectively. Our results indicate that the new scaffolds selected using a virtual screening process exhibit potential as novel QC inhibitors.

Isolation and Identification of Chemical Compounds from Agaricus blazei Murrill and Their In Vitro Antifungal Activities.

This study explores the antifungal properties of Agaricus blazei Murrill, a valuable medicinal and edible fungus. Six compounds (1-6) were first isolated from A. blazei using various isolation techniques and identified using spectroscopic methods. These compounds include linoleic acid, 1,1'-oxybis(2,4-di-tert-butylbenzene), glycerol monolinoleate, volemolide (17R)-17-methylincisterol, (24s)-ergosta-7-en-3-ol, and dibutyl phthalate. This study also assesses the antifungal activities of these compounds against Trichophyton mentagrophology, Trichophyton rubrum, Candida albicans, and Cryptococcus neoformans. The results demonstrate varied sensitivities against these pathogenic fungi, with compound 2 showing significant inhibition against T. mentagrophology, compound 3 showing significant inhibition against T. rubrum, and compound 6 showing significant inhibition against C. albicans. This study underscores the medicinal potential of A. blazei as an antifungal agent and sheds light on its valuable research implications.

Cytotoxic Compounds from Belamcanda chinensis (L.) DC Induced Apoptosis in Triple-Negative Breast Cancer Cells.

Four compounds (1, 5, 7, and 8) were first isolated from the genus Belamcanda Adans. nom. conserv., and six known compounds (2-4, 6, 9, and 10) were isolated from the rhizome of Belamcanda chinensis (L.) DC. Their structures were confirmed by spectroscopic data. Herein, compounds 1-10 were rhapontigenin, trans-resveratrol, 5,7,4'-trihydroxy-6,3',5'-trimethoxy-isoflavone, irisflorentin, 6-hydroxybiochannin A, iridin S, pinoresinol, 31-norsysloartanol, isoiridogermanal, and iristectorene B, respectively. All compounds were evaluated for their antiproliferative effects against five tumor cell lines (BT549, 4T1, MCF7, MDA-MB-231, and MDA-MB-468). Among them, compound 9 (an iridal-type triterpenoid) showed the highest activity against 4T1 and MDA-MB-468 cells. Further studies displayed that compound 9 inhibited cell metastasis, induced cells cycle arrest in the G1 phase, exhibited significant mitochondrial damage in 4T1 and MDA-MB-468 cells including excess reactive oxygen species, decreased mitochondrial membrane potential, and induced 4T1 and MDA-MB-468 cell apoptosis for the first time. In summary, these findings demonstrate that compound 9 exerts promising potential for triple-negative breast cancer treatment and deserves further evaluation.

Design, synthesis and anti-AD effects of dual inhibitor targeting glutaminyl cyclase/GSK-3ß.

Alzheimer's disease (AD), multifactorial disease, is recognized as one of the most common forms of dementia, and the efficacy of anti-AD drugs is limited clinically. Up-regulated glutaminyl cyclase (QC) and glycogen synthase kinase-3ß (GSK-3ß) have been identified as two critical elements involved in AD recently. Here, a series of novel chemicals containing maleimide and imidazole motif were designed and synthesized as dual inhibitors targeting QC and GSK-3ß. Based on primary screening, compound 2 (2.26 µM), 5 (2.37 µM), 8 (1.34 µM), 21 (2.44 µM), 25 (0.36 µM), 27 (1.76 µM), 28 (1.04 µM), 33 (2.08 µM) and 34 (2.33 µM) exhibited notable human QC (hQC) inhibitory potency, while compound 1 (0.014 µM), 7 (0.04 µM), 8 (0.057 µM), 19 (0.034 µM), 24 (0.014 µM), 32 (0.032 µM), 38 (0.051 µM), 39 (0.044 µM), 44 (0.048 µM), 47 (0.011 µM), 49 (0.021 µM) and so on showed remarkable GSK-3ß inhibitory activities. And as expected, these chemicals possessed significant inhibitory potency on both hQC and GSK-3ß, such as compound 1 (2.80 and 0.014 µM), 8 (1.34 and 0.057 µM), 25 (0.36 and 0.15 µM), 27 (1.76 and 0.069 µM), 28 (1.04 and 0.090 µM), 33 (2.08 and 0.19 µM), 34 (2.33 and 0.11 µM), 35 (2.55 and 0.14 µM), 36 (2.34 and 0.11 µM), etc. Subsequent in vivo studies demonstrated that compound 8 attenuated cognitive deficits and decreased the anxiety-like behavior in 3 × Tg-AD mice. The treatment decreased both pE-Aß and Aß accumulation by inhibiting the activity of QC, and decreased the hyperphosphorylation of Tau by reducing the levels of GSK-3ß in the brains of AD mice. Results obtained in this research suggested that these novel compounds could be supposed as potential anti-AD agents targeting QC and GSK-3ß.

Near-infrared AIE-active phosphorescent iridium(III) complex for mitochondria-targeted photodynamic therapy.

Mitochondria-targeted photodynamic therapy (PDT) has recently been recognized as a promising strategy for effective cancer treatment. In this work, a mitochondria-targeted near-infrared (NIR) aggregation-induced emission (AIE)-active phosphorescent Ir(III) complex (Ir1) is reported with highly favourable mitochondria-targeted bioimaging and cancer PDT properties. Complex Ir1 has strong absorption in the visible light region (∼500 nm) and can effectively produce singlet oxygen (1O2) under green light (525 nm) irradiation. It preferentially accumulates in the mitochondria of human breast cancer MDA-MB-231 cells as revealed by colocalization analysis. Complex Ir1 displays high phototoxicity toward human breast cancer MDA-MB-231 cells and mouse breast cancer 4T1 cells. Complex Ir1 induces reactive oxygen species (ROS) production, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in MDA-MB-231 cells upon photoirradiation, leading to apoptotic cell death. The favorable PDT performance of Ir1in vivo has been further demonstrated in tumour-bearing mice. Together, the results suggest that Ir1 is a promising photosensitizer for mitochondria-targeted imaging and cancer phototherapy.

Upregulation of Glutaminyl Cyclase Contributes to ERS-Induced Apoptosis in PC12 Cells.

Glutaminyl cyclase (QC) is responsible for converting the N-terminal glutaminyl and glutamyl of the proteins into pyroglutamate (pE) through cyclization. It has been confirmed that QC catalyzes the formation of neurotoxic pE-modified Aß in the brain of AD patients. But the effects of upregulated QC in diverse diseases have not been much clear until recently. Here, RNA sequencing was applied to identify differentially expressed genes (DEGs) in PC12 cells with QC overexpressing or knockdown. A total of 697 DEGs were identified in QC overexpressing cells while only 77 in QC knockdown cells. Multiple bioinformatic approaches revealed that the DEGs in QC overexpressing group were enriched in endoplasmic reticulum stress (ERS) related signaling pathways. The gene expression patterns of 23 DEGs were confirmed by RT-qPCR, in which the genes related to ERS showed the highest consistency. We also revealed the protein levels of GRP78, PERK, CHOP, and PARP-1, and caspase family was significantly upregulated by overexpressing QC. Moreover, overexpressing QC significantly increased apoptosis of PC12 cells in a time dependent manner. However, no significant alteration was observed in QC knockdown cells. Therefore, our study indicated that upregulated QC could induce ERS and apoptosis, which consequently trigger diseases by catalyzing the generation of pE-modified mediators.

Development of a TaqMan-based multiplex real-time PCR for simultaneous detection of four feline diarrhea-associated viruses.

Since their recent discovery, the prevalence of novel feline enteric viruses, including feline bocavirus 1 (FBoV-1), feline astrovirus (FeAstV), and feline kobuvirus (FeKoV), has been reported in China. Co-infections of these viruses with feline parvovirus (FPV) are common causes of diarrhea in cats. Viral co-infections are difficult to identify because of their non-specific clinical signs. To detect and identify these viruses, a quick and specific pathogen-testing approach is required. Here, we establish a real-time PCR (qPCR) based on multiple TaqMan probes for the simultaneous detection of FBoV-1, FeAstV, FeKoV, and FPV. Specific primers and TaqMan fluorescent probes were designed to ensure specificity. The results showed that the detection limit of single qPCR was up to 10 copies, and the detection limit of multiplex qPCR was up to 100 copies, with correlation coefficients >0.995 in all cases. Clinical sample detection revealed a 25.19% (34/135) total rate of co-infection among the viruses and a 1.48% (2/135) quadruple infection rate. Thus, this multiplex qPCR approach can serve as a quick, sensitive, and specific diagnostic tool for FBoV-1, FeAstV, FeKoV, and FPV identification, and it may be utilized for routine surveillance of these emerging and reemerging feline enteric viruses.

Recent advances in mesoporous silica nanoparticle-based targeted drug-delivery systems for cancer therapy.

Targeted drug-delivery systems are a growing research topic in tumor treatment. In recent years, mesoporous silica nanoparticles (MSNs) have been extensively studied and applied in noninvasive and biocompatible drug-delivery systems for tumor therapy due to their outstanding advantages, which include high surface area, large pore volume, tunable pore size, easy surface modification and stable framework. The advances in the application of MSNs for anticancer drug targeting are covered and highlighted in this review, and the challenges and prospects of MSN-based targeted drug-delivery systems are discussed. This review provides new insights for researchers interested in targeted drug-delivery systems against cancer.

The Leaves of Cyclocarya paliurus: A Functional Tea with Preventive and Therapeutic Potential of Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) has become a universal and chronic global public health concern and causes multiple complex complications. In order to meet the rapidly growing demand for T2DM treatment, increased research has been focused on hypoglycemic drugs. Cyclocarya paliurus (Batal.) Iljinsk is the only living species of the genus Cyclocarya Iljinskaja, whose leaves have been extensively used as a functional tea to treat obesity and diabetes in China. An enormous amount of very recent pharmacological research on the leaves of C. paliurus has demonstrated that they carry out numerous biological activities, such as hypoglycemic, anti-inflammatory, and intestinal microbiota regulation. Multiple in vitro and in vivo studies have also shown that the extracts of C. paliurus leaves are innocuous and safe. This study aims to provide an up-to-date review of the botany, traditional uses, phytochemistry, pharmacological effects against diabetes, toxicology, and clinical studies of C. paliurus leaves, in hopes of promoting a better understanding of their role in the prevention and treatment of T2DM.

METTL7B contributes to the malignant progression of glioblastoma by inhibiting EGR1 expression.

Glioblastoma (GBM), a predominant central nervous system (CNS) malignancy, is correlated with high mortality and severe morbidity. Mammalian methyltransferase-like 7B (METTL7B) as a methyltransferase has been identified to participate in cancer progression. However, its function in GBM is elusive. Accordingly, we aimed to explore the effect of METTL7B on GBM. The expression of METTL7B and EGR2 in GBM patients and GBM cells were detected by qPCR, western blots and immunohistochemical staining. Cell viability was assessed by CCK-8 assays. Cell proliferation was determined by EdU, colony formation, and tumor sphere formation assays. METTL7B shRNA was injected into the Balb/c nude mice. The size and weight of isolated tumor was measured. And the expression levels of Ki67, METTL7B and EGR1 were examined by immunohistochemical staining. METTL7B was significantly elevated, while EGR1 was downregulated in clinical GBM tissues. METTL7B upregulation was associated with the low overall survival of GBM patients. Moreover, METTL7B depletion remarkably attenuated GBM cell proliferation. Mechanistically, METTL7B overexpression inhibited EGR1 expression in GBM cells. EGR1 knockdown rescued the inhibitory effect of METTL7B depletion on GBM cell proliferation. Meanwhile, METTL7B depletion arrested more GBM cells at the G0/G1, but fewer cells at the S phase, which EGR1 knockdown reversed these effects. Furthermore, tumorigenicity analysis revealed that METTL7B promotes tumor growth of GBM cells in vivo. METTL7B contributes to the malignant progression of GBM by inhibiting EGR1 expression. METTL7B and EGR1 may be utilized as the treatment targets for GBM therapy.

Establishment of SYBR green I-based quantitative real-time polymerase chain reaction for the rapid detection of a novel Chaphamaparvovirus in cats.

Feline parvovirus causes infectious diseases, and Chaphamaparvovirus is a novel type of feline parvovirus. The present study aims to establish a method that can be used in clinical rapid detection of feline Chaphamaparvovirus (FeChPV), for facilitate the timely and effective diagnosis and treatment of sick animals and shorten the diagnosis time of clinical diseases. The experimental samples in this study are from 20 cats undergoing physical examination in Hefei Xin'an Animal Hospital. An SYBR Green I-based qPCR assay was performed to detect FeChPV. A pair of specific primers was designed based on the VP1 gene to perform the assay. The detection assay showed high sensitivity with a detection limit of 1.07 × 101 copies/µL and high specificity for detection of only the target virus. The coefficients of C t value variation were calculated to assess the reproducibility of the qPCR assay, and the inter- and intra-assay ranged from 0.21 to 0.67% and 0.10 to 0.56%, respectively. The result of clinical sample detection showed that the infection rate of FeChPV in 124 samples detected using qPCR assay was higher than that with conventional PCR. The established qPCR assay could be a low-cost, convenient, and reliable method to detect FeChPV in clinical practice.

P2Y1R Ligation Suppresses Th17 Cell Differentiation and Alleviates Colonic Inflammation in an AMPK-Dependent Manner.

P2Y1 receptor is a G-protein-coupled receptor that plays a critical role in the immune response of inflammatory bowel diseases. However, its regulatory effects on CD4+ T cell response have not been fully elucidated. The study aimed to characterize the role of P2Y1R in Th17 cell differentiation and colonic inflammation. Our results demonstrated that P2Y1R was significantly increased in the splenocytes of colitic mice, which was positively associated with the expression of RORγt and IL-17A. P2Y1R deficiency significantly ameliorated DSS-induced colitis and its Th17 responses. In parallel, P2Y1R deficiency greatly impaired the differentiation of Th17 cell, down-regulated the mRNA expression of IL-17A and RORγt, and protein expression of RORγt in vitro. More importantly, it was found that P2Y1R deficiency markedly increased AMPK phosphorylation of Th17 polarized CD4+ T cells, and antagonist of AMPK significantly reversed the inhibitory effect of P2Y1R deficiency on Th17 cell generation in vivo and in vitro. Overall, these findings demonstrated that P2Y1R deficiency could suppress Th17 cell differentiation in an AMPK-dependent manner to ameliorate colitis, and P2Y1R can act as an important regulator of Th17 cell differentiation to control colonic inflammation.

Phytochemicals as regulators of Th17/Treg balance in inflammatory bowel diseases.

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder that is difficult to cure and characterized by periods of relapse. To face the challenges of limited treatment strategies and drawbacks of conventional medications, developing new and promising strategies as well as safe and effective drugs for treatment of IBD has become an urgent demand for clinics. The imbalance of Th17/Treg is a crucial event for the development of IBD, and studies have verified that correcting the imbalance of Th17/Treg is an effective strategy for preventing and treating IBD. Recently, a growing body of studies has indicated that phytochemicals derived from natural products are potent regulators of Th17/Treg, and exert preferable protective benefits against colonic inflammation. In this review, the great potential of anti-colitis agents derived from natural products through targeting Th17/Treg cells and their action mechanisms for the treatment or prevention of IBD in recent research is summarized, which may help further the development of new drugs for IBD treatment.

Therapeutic potential of Moringa oleifera seed polysaccharide embedded silver nanoparticles in wound healing.

Wound healing is a complicated process that influences patient's life quality. Plant-based polysaccharide has recently gained interest in its use in wound dressing materials because of its biological compatibility, natural abundance, and ideal physiochemical properties. The present study reveals the potential of polysaccharide isolated from Moringa oleifera seed (MOS-PS) and its nanocomposite with silver (MOS-PS-AgNPs) as alternative materials for wound dressing. First, MOS-PS was isolated and structurally characterized by TLC, HPLC, FTIR, NMR, and GPC analyses. A green and simple method was used to synthesize AgNPs using MOS-PS as a stabilizing and reducing agent. The size, morphology, and structure of the MOS-PS-AgNPs were characterized by UV-Vis spectroscopy, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and zeta potential analysis. The results showed that the MOS-PS-AgNPs were spherically shaped, having no cytotoxicity toward mouse fibroblasts cells and promoting their in-vitro migration. Moreover, the MOS-PS-AgNPs displayed strong anti-microbial activity against wound infectious pathogenic bacteria. Finally, the MOS-PS-AgNPs were used for dressing animal wounds and its preliminary mechanism was studied by RT-PCR and histological analysis. The results showed that the MOS-PS-AgNPs can promote wound contraction and internal tissue growth well. Overall, our results indicated that the MOS-PS-AgNPs might be an excellent candidate for use as an optimal wound dressing material.

Glutaminyl Cyclase, Diseases, and Development of Glutaminyl Cyclase Inhibitors.

Pyroglutamate (pE) modification, catalyzed mainly by glutaminyl cyclase (QC), is prevalent throughout nature and is particularly important in mammals including humans for the maturation of hormones, peptides, and proteins. In humans, the upregulation of QC is involved in multiple diseases and conditions including Alzheimer's disease, Huntington's disease, melanomas, thyroid carcinomas, accelerated atherosclerosis, septic arthritics, etc. This upregulation catalyzes the generation of modified mediators such as pE-amyloid beta (Aß) and pE-chemokine ligand 2 (CCL2) peptides. Not surprisingly, QC has emerged as a reasonable target for the development of therapeutics to combat these diseases and conditions. In this manuscript the deleterious effects of upregulated QC resulting in disease manifestation are reviewed, along with progress on the development of QC inhibitors.

Regulation of ferroptosis by bioactive phytochemicals: Implications for medical nutritional therapy.

Ferroptosis is an iron- and lipotoxicity-dependent regulated cell death that has been implicated in various diseases, such as cancer, neurodegeneration and stroke. The biosynthesis of phospholipids, coenzyme Q10, and glutathione, and the metabolism of iron, amino acids and polyunsaturated fatty acid, are tightly associated with cellular sensitivity to ferroptosis. Up to now, only limited drugs targeting ferroptosis have been documented and exploring novel effective ferroptosis-modulating compound is needed. Natural bioactive products are conventional resources for drug discovery, and some of them have been clinically used against cancers and neurodegenerative diseases as dietary supplements or pharmaceutic agents. Notably, increasing evidence demonstrates that natural compounds, such as saponins, flavonoids and isothiocyanates, can either induce or inhibit ferroptosis, further expanding their therapeutic potentials. In this review, we highlight current advances of the emerging molecular mechanisms and disease relevance of ferroptosis. We also systematically summarize the regulatory effects of natural phytochemicals on ferroptosis, and clearly indicate that saponins, terpenoids and alkaloids induce ROS- and ferritinophagy-dependent ferroptosis, whereas flavonoids and polyphenols modulate iron metabolism and nuclear factor erythroid 2-related factor 2 (NRF2) signaling to inhibit ferroptosis. Finally, we explore their clinical applications in ferroptosis-related diseases, which may facilitate the development of their dietary usages as nutraceuticals.

Peroxide- and transition metal-free electrochemical synthesis of α,ß-epoxy ketones.

A novel electrochemical method for the synthesis of α,ß-epoxy ketones is reported. With KI as the redox mediator, methyl ketones reacted with aldehydes under peroxide- and transition metal-free electrolytic conditions and afforded α,ß-epoxy ketones in one pot (36 examples, 52-90% yield). This safe and environmental-friendly method has a broad substrate scope and can readily provide a variety of α,ß-epoxy ketones in gram-scales for evaluation of their anti-cancer activities.