Atomically dispersed bimetallic active sites as HO self-supplied nanozyme for effective chemodynamic therapy, chemotherapy and starvation therapy.

Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) is severely hindered by insufficient intracellular HO level that seriously deteriorates antitumor efficacy, albeit with its extensively experimental and theoretical research. Herein, we designed atomically dispersed FeCo dual active sites anchored in porous carbon polyhedra (termed FeCo/PCP), followed by loading with glucose oxidase (GOx) and anticancer doxorubicin (DOX), named FeCo/PCP-GOx-DOX, which converted glucose into toxic hydroxyl radicals. The loaded GOx can either decompose glucose to self-supply HO or provide fewer nutrients to feed the tumor cells.

Fe single atoms encapsulated in N, P-codoped carbon nanosheets with enhanced peroxidase-like activity for colorimetric detection of methimazole.

Excessive use of antithyroid drug methimazole (MMI) in pharmaceutical samples can cause hypothyroidism and symptoms of metabolic decline. Hence, it is urgent to develop rapid, low cost and accurate colorimetric method with peroxidase-like nanozymes for determination of MMI in medical, nutrition and pharmaceutical studies. Herein, Fe single atoms were facilely encapsulated into N, P-codoped carbon nanosheets (Fe SAs/NP-CSs) by a simple pyrolysis strategy, as certified by a series of characterizations.

Fe-Ni dual-single atoms nanozyme with high peroxidase-like activity for sensitive colorimetric and fluorometric dual-mode detection of cholesterol.

Cholesterol is widely existed in nerve myelin sheath and various membrane structures, whose abnormal level would deteriorate human cells or even cause diseases. Herein, Fe-Ni dual-single-atom nanozyme was efficiently incorporated into N-doped carbon nanosheets (FeNi DSAs/N-CSs) by a simple calcination method. Its nanozyme activity and catalytic mechanism were investigated in details.

Confined synthesis of ternary FeCoMn single-atom nanozyme in N-doped hollow mesoporous carbon nanospheres for synergistic chemotherapy and chemodynamic cancer therapy.

Recently, nanozymes show increasing biological applications and promising possibilities for therapeutic intervention, while their mediated therapeutic outcomes are severely compromised due to their insufficient catalytic activity and specificity. Herein, ternary FeCoMn single atoms were incorporated into N-doped hollow mesoporous carbon nanospheres by in situ confinement pyrolysis at 800 °C as high-efficiency nanozyme. The confinement strategy endows the as-prepared nanozyme with the enhanced catalase- and oxidase-like activities.

N-Doped Carbon Nanotubes Supported Fe-Mn Dual-Single-Atoms Nanozyme with Synergistically Enhanced Peroxidase Activity for Sensitive Colorimetric Detection of Acetylcholinesterase and Its Inhibitor.

Monitoring acetylcholinesterase (AChE) and its inhibitors is of importance for early diagnosis and therapy of neurological diseases. Herein, N-doped carbon nanotubes supported Fe-Mn dual-single-atoms (FeMn DSAs/N-CNTs) were fabricated by a simple pyrolysis, as thoroughly figured out by a series of the characterization techniques. The peroxidase-like activity of FeMn DSAs/N-CNTs was investigated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to generate rich hydroxyl radicals (·OH) in the HO system, which effectively catalyzed colorless TMB oxidation to blue oxidized TMB (ox-TMB).

Bimetallic AuPt alloy/rod-like CeO nanojunctions with high peroxidase-like activity for colorimetric sensing of organophosphorus pesticides.

Organophosphorus pesticides (OP) have extensive applications in agriculture, while their overuse causes inevitable residues in food, soil, and water, ultimately being harmful to human health and even causing diverse dysfunctions. Herein, a novel colorimetric platform was established for quantitative determination of malathion based on peroxidase mimic AuPt alloy decorated on CeO nanorods (CeO@AuPt NRs). The synthesized nanozyme oxidized colorless 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of HO.

BMP-7 ameliorates partial epithelial-mesenchymal transition by restoring SnoN protein level via Smad1/5 pathway in diabetic kidney disease.

Tubulointerstitial fibrosis (TIF) is involved in the development of diabetic kidney disease (DKD). Transforming growth factor β1 (TGF-β1) is involved in the extensive fibrosis of renal tissue by facilitating the partial epithelial-mesenchymal transition (EMT), increasing the synthesis of extracellular matrix (ECM), inhibiting degradation, inducing apoptosis of renal parenchyma cells, and activating renal interstitial fibroblasts and inflammatory cells. Recent studies indicated that bone morphogenetic protein-7 (BMP-7) upregulated the expression of endogenous SnoN against renal TIF induced by TGF-β1 or hyperglycemia.

Blood glucose control contributes to protein stability of Ski-related novel protein N in a rat model of diabetes.

Ski-related novel protein N (SnoN) negatively regulates the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway and is present at a low level during diabetic nephropathy (DN), but its underlying regulatory mechanism is currently unknown. The present study aimed to assess the effects of insulin-controlled blood glucose on renal SnoN expression and fibrosis in rats with diabetes mellitus (DM). Streptozotocin-induced DM rats were treated with insulin glargine (INS group) following successful model establishment.

Identification of YAP1 as a novel downstream effector of the FGF2/STAT3 pathway in the pathogenesis of renal tubulointerstitial fibrosis.

Chronic kidney disease is a global health problem and eventually develops into an end-stage renal disease (ESRD). It is now widely believed that renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of ESRD. Renal tubular epithelial-mesenchymal transition (EMT) is an important cause of TIF.

The role of CDX2 in renal tubular lesions during diabetic kidney disease.

Renal tubules are vulnerable targets of various factors causing kidney injury in diabetic kidney disease (DKD), and the degree of tubular lesions is closely related to renal function. Abnormal renal tubular epithelial cells (RTECs) differentiation and depletion of cell junction proteins are important in DKD pathogenesis. Caudal-type homeobox transcription factor 2 (CDX2), represents a key nuclear transcription factor that maintains normal proliferation and differentiation of the intestinal epithelium.

EI24 alleviates renal interstitial fibrosis through inhibition of epithelial-mesenchymal transition and fibroblast activation.

Etoposide-induced 2.4 (EI24) exerts tumor suppressor activity through participating in cell apoptosis, autophagy, and inflammation. However, its role in renal diseases has not been elucidated.

Autophagy-related protein EI24 delays the development of pulmonary fibrosis by promoting autophagy.

Etoposide-induced protein 2.4 (EI24) is an autophagy-associated protein and acts as a tumor suppressor. However, its role in tissue fibrosis remains unknown.

Smad2 and Smad3 play antagonistic roles in high glucose-induced renal tubular fibrosis via the regulation of SnoN.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes mellitus.The main pathological features of DN include glomerular sclerosis and renal tubular interstitial fibrosis, which results in epithelial mesenchymal transition (EMT) and excessive extracellular matrix (ECM) deposition.Transforming growth factor-β1(TGF-β1) is a critical factor that regulates the manifestation of renal fibrosis.

BMP-7 inhibits renal fibrosis in diabetic nephropathy via miR-21 downregulation.

Epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in renal tubular epithelial cells are critical to diabetic nephropathy (DN) pathogenesis, but the underlying mechanisms remain undefined. Bone morphogenetic protein 7 (BMP-7) inhibits EMT and ECM accumulation in renal tubular epithelial cells cultured in presence of high glucose. Meanwhile, miRNA-21 (miR-21) downregulates Smad7, promoting EMT and ECM deposition.

TAK1 may promote the development of diabetic nephropathy by reducing the stability of SnoN protein.

Aims: This study aimed to investigate the role of transforming growth factor-β-activated protein kinase 1(TAK1) in the development of diabetic nephropathy (DN) by regulating the protein stability of Ski-related novel protein N(SnoN).

Main Methods: A combination of in vivo and in vitro model systems was used to investigate how TAK1 regulated the expression of SnoN protein in DN. The study determined the effects of modulating the expression or activity of TAK1 on the SnoN protein level and its influence on the epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition.

Ski-related novel protein suppresses the development of diabetic nephropathy by modulating transforming growth factor-β signaling and microRNA-21 expression.

Unveiling the mechanisms that drive the pathological phenotypes of diabetic nephropathy (DN) could help develop new effective therapeutics for this ailment. Transforming growth factor-β1 (TGF-β1)/Smad3 signaling is aberrantly induced in DN, leading to elevated microRNA-21 (miR-21) expression and tissue fibrosis. Ski-related novel protein (SnoN) negatively regulates the TGF-β pathway, but the relationship between SnoN and miR-21 has not been described in the context of DN.

[Alpha-lipoamide inhibits renal inflammation and collagen 4 production in diabetic rats and its mechanism].

Objective To observe the expression of Notch2, NLR family pyrin domain containing 3 (NLRP3) in the renal tissue of rats with diabetes mellitus (DM), and the effects of alpha-lipoamide (ALM) on the expression of Notch2, Toll-like receptor 4 (TLR4), NLRP3 and collagen, to explore the possible protective mechanism of ALM against diabetic renal inflammation and renal fibrosis. Methods The DM rat models were induced by the injection of streptozotocin (STZ) and divided into DM group and ALM group. Meanwhile, normal control (NC) group was set up.