Inhibition of STAT3-NF-κB pathway facilitates SSPH I-induced ferroptosis in HepG2 cells.

Hepatocellular carcinoma (HCC), a highly lethal solid tumor, has shown responsiveness to ferroptosis inducers, presenting new avenues in cancer treatment. Our study focuses on the roles of STAT3 and Nf-κB in regulating ferroptosis, particularly their interaction in this process. Using HepG2 cells, we employed specific inhibitors (Stattic for STAT3 and Bay11-7082 for Nf-κB) and a ferroptosis inducer, SSPH I, to dissect their collective impact on ferroptosis. Our findings reveal that inhibiting STAT3 and Nf-κB enhances ferroptosis and cytotoxicity induced by SSPH I. This is mechanistically linked to alterations in iron metabolism-related proteins and GPX4 resulting from SSPH I action, which consequently triggers a STAT3-dependent activation of Nf-κB. The inhibition of STAT3 and Nf-κB led to increased intracellular ROS, MDA, and Fe2+, along with significant GSH depletion, thereby intensifying lipid peroxidation and iron overload in HepG2 cells. This study offers a deeper understanding of the ferroptosis mechanisms in HCC. It highlights the therapeutic potential of targeting STAT3 and Nf-κB pathways to enhance the efficacy of ferroptosis-based treatments.

SCF/C-kit drives spermatogenesis disorder induced by abscopal effects of cranial irradiation in mice.

Cranial radiotherapy is a major treatment for leukemia and brain tumors. Our previous study found abscopal effects of cranial irradiation could cause spermatogenesis disorder in mice. However, the exact mechanisms are not yet fully understood. In the study, adult male C57BL/6 mice were administrated with 20 Gy X-ray cranial irradiation (5 Gy per day for 4 days consecutively) and sacrificed at 1, 2 and 4 weeks. Tandem Mass Tag (TMT) quantitative proteomics of testis was combined with bioinformatics analysis to identify key molecules and signal pathways related to spermatogenesis at 4 weeks after cranial irradiation. GO analysis showed that spermatogenesis was closely related to oxidative stress and inflammation. Severe oxidative stress occurred in testis, serum and brain, while serious inflammation also occurred in testis and serum. Additionally, the sex hormones related to hypothalamic-pituitary-gonadal (HPG) axis were disrupted. PI3K/Akt pathway was activated in testis, which upstream molecule SCF/C-Kit was significantly elevated. Furthermore, the proliferation and differentiation ability of spermatogonial stem cells (SSCs) were altered. These findings suggest that cranial irradiation can cause spermatogenesis disorder through brain-blood-testicular cascade oxidative stress, inflammation and the secretory dysfunction of HPG axis, and SCF/C-kit drive this process through activating PI3K/Akt pathway.

Effects of Viscum coloratum (Kom.) Nakai on collagen-induced rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum coloratum (Kom.) Nakai has been traditionally used in China for nearly a thousand years to treat rheumatic diseases. However, its efficacy and mechanisms in treating rheumatoid arthritis (RA) have not been demonstrated. AIM OF THE STUDY: To investigate the anti-arthritic effects and molecular mechanisms of Viscum coloratum (Kom.) Nakai on collagen-induced arthritic mice through network pharmacology technology and experimental validation. MATERIALS AND METHODS: First, the main ingredients of the extract of Viscum coloratum (Kom.) Nakai (EVC) were identified through chemical composition characterization using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS). Then, the collagen-induced arthritis (CIA) model was established in DBA/1 J mice and the ameliorative effects of EVC on the progression of CIA mice were evaluated by oral treatment with different doses of the EVC for 28 days. After that, cytokine antibody microarray assay was used to detect the levels of multiple inflammation-related cytokines and chemokines in each group, and performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Subsequently, the potential target for the effective chemical components of EVC in treating RA was identified using various databases. Additionally, a drug-disease target protein-protein interaction network (PPI) was conducted using Cytoscape for visualization and clustering, while GO and KEGG enrichment analyses were performed with the Metascape database. Finally, identified phenotypes and targets by network pharmacology analysis were experimentally validated in vivo. RESULTS: Treatment with EVC significantly suppressed the severity of CIA with a dramatic reduction of paw swelling, arthritis index, levels of IgGs (IgG, IgG1, IgG2a, and IgG2b), multi-inflammation-related cytokines and chemokines on the progression of CIA. Histopathological examinations showed EVC could markedly inhibit inflammatory cell infiltration, tartrate-resistant acid phosphatase (TRAP) activity of osteoclast, and bone destruction. Furthermore, GO and KEGG enrichment analyses revealed that EVC could ameliorate RA by inhibiting osteoclast differentiation and regulating multiple signaling pathways including Osteoclast differentiation, IL-17, and TNF. PPI network analysis demonstrated that AKT1, MMP9, MAPK3, and other genes were highly related to EVC in treating RA. Finally, we proved that EVC could inhibit the expression of NFTAc1, MMP9, Cathepsin K, and AKT which were closely related to osteoclast activity. CONCLUSIONS: EVC could treat RA through multiple components, multiple targets, and multiple pathways. The present study demonstrated the therapeutic efficacy of EVC and its molecular mechanisms in treating RA, indicating that it would be a potent candidate as a novel botanical drug for further investigation.

Steroidal saponin SSPH I induces ferroptosis in HepG2 cells via regulating iron metabolism.

Hepatocellular carcinoma (HCC) is a common type of solid liver carcinoma. Regulating ferroptosis is important for the treatment of HCC. SSPH I is an anti-HCC steroidal saponin isolated from Schizocapsa plantaginea Hance. In this study, we found that SSPH I exerted significant anti-proliferation and anti-migration effects on HepG2 cell, ferroptosis inhibitor ferrostatin-1 or iron chelator ciclopirox partly attenuated the effect of SSPH I. SSPH I also induced apoptosis and G2/M phase cell cycle arrest. ROS accumulation, glutathione depletion and malondialdehyde accumulation were detected after SSPH I treatment, which leads to lipid peroxidation. Ferrostatin-1 or ciclopirox showed a significant antagonist effect towards SSPH I induced lipid peroxidation. Furthermore, typical morphologic changes of ferroptosis, such as increasing density of mitochondrial membrane and reduction of mitochondrial cristae were observed in HepG2 cells after SSPH I treatment. SSPH I does not regulate the xCT protein. Interestingly, SSPH I elevated the expression levels of SLC7A5, which is the negative regulator of ferroptosis. In contrast, SSPH I upregulated the expression of TFR and Fpn proteins, leading to the accumulation of Fe2+. Ferrostatin-1 and ciclopirox presented a similar antagonist effect on SSPH I. In conclusion, our research first reveals that SSPH I induced ferroptosis in HepG2 cells. In addition, our results suggest that SSPH I induces ferroptosis by causing iron overload in HepG2 cells.

The protective effects of dietary Clostridium butyricum supplementation on hepatic ischemia reperfusion injury in rats.

PURPOSE: This study investigated the effects of oral administration of Clostridium butyricum (C. butyricum) on inflammation, oxidative stress, and gut flora in rats with hepatic ischemia reperfusion injury (HIRI). METHODS: The rats from C. butyricum group were given C. butyricum for 5 days. Then, hepatic ischemia for 30 min and reperfusion for 6 h were performed in all the rats. After the animals were sacrificed, alanine transaminase (ALT), aspartate aminotransferase (AST), lipopolysaccharide (LPS) in serum, short-chain fatty acids (SCFAs), and gut microbiota composition in feces, and malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), Toll-like receptor 4 (TLR4), nuclear factor-kappa Bp65 (NF-κBp65) and histological analysis in the liver were performed. RESULTS: The rats given C. butyricum showed decreased ALT, AST, LPS, and MDA; improved GSH and histological damage; changes in SCFAs; declined TNF-α, IL-6, TLR4, and pNF-κBp65/NF-κBp65; and changes in the gut microbial composition, which decreased the Firmicutes/Bacteroidetes ratio and increased the relative abundance (RA) of probiotics. CONCLUSIONS: C. butyricum supplementation protected against HIRI by regulating gut microbial composition, which contributed to the decreased LPS and attenuation of inflammation and oxidative stress. These indicate C. butyricum may be a potent clinical preoperative dietary supplement for HIRI.

Synthesis and shaping of metal-organic frameworks: a review.

Metal-organic frameworks (MOFs) possess excellent advantages, such as high porosity, large specific surface area, and an adjustable structure, showing good potential for applications in gas adsorption and separation, catalysis, conductivity, sensing, magnetism, etc. However, they still suffer from significant limitations in terms of the scale-up synthesis and shaping, hindering the realization of large-scale commercial applications. Despite some attempts having been devoted to addressing this, challenges remain. In this paper, we outline the advantages and drawbacks of existing synthetic routes such as electrochemistry, microwave, ultrasonic radiation, green solvent reflux, room temperature stirring, steam-assisted transformation, mechanochemistry, and fluid chemistry in terms of scale-up production. Then, the shaping methods of MOFs such as extrusion, mechanical compaction, rolling granulation, spray drying, gel technology, embedded granulation, phase inversion, 3D printing and other shaping methods for the preparation of membranes, coatings and nanoparticles are discussed. Finally, perspectives on the large-scale synthesis and shaping of MOFs are also proposed. This work helps provide in-depth insight into the scale-up production and shaping process of MOFs and boost commercial applications of MOFs.

The protective effects of dietary Clostridium butyricum supplementation on hepatic ischemia reperfusion injury in rats

Purpose: This study investigated the effects of oral administration of Clostridium butyricum (C. butyricum) on inflammation, oxidative stress, and gut flora in rats with hepatic ischemia reperfusion injury (HIRI). Methods: The rats from C. butyricum group were given C. butyricum for 5 days. Then, hepatic ischemia for 30 min and reperfusion for 6 h were performed in all the rats. After the animals were sacrificed, alanine transaminase (ALT), aspartate aminotransferase (AST), lipopolysaccharide (LPS) in serum, short-chain fatty acids (SCFAs), and gut microbiota composition in feces, and malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), Toll-like receptor 4 (TLR4), nuclear factor-kappa Bp65 (NF-κBp65) and histological analysis in the liver were performed. Results: The rats given C. butyricum showed decreased ALT, AST, LPS, and MDA; improved GSH and histological damage; changes in SCFAs; declined TNF-α, IL-6, TLR4, and pNF-κBp65/NF-κBp65; and changes in the gut microbial composition, which decreased the Firmicutes/Bacteroidetes ratio and increased the relative abundance (RA) of probiotics. Conclusions: C. butyricum supplementation protected against HIRI by regulating gut microbial composition, which contributed to the decreased LPS and attenuation of inflammation and oxidative stress. These indicate C. butyricum may be a potent clinical preoperative dietary supplement for HIRI.

Successful treatment of advanced pulmonary sarcomatoid carcinoma with the PD-1 inhibitor toripalimab: A case report.

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung carcinoma (NSCLC), which characterized by insensitive to conventional radiotherapy and chemotherapy and poor prognosis. Except MET exon 14 alterations and other oncogene mutations, PSC commonly harbor high tumor mutational burden (TMB) and high level of PD-L1, which provide new therapeutic opportunities. Toripalimab (JS001) is IgG4 monoclonal antibody targeting PD-1, which has been approved for treatment of patients with metastatic melanoma after previous systemic therapy. PD-1 combined with radiotherapy has been tried in several cancer types. CASE PRESENTATION: We reported a case of a PSC patient with PD-L1 overexpression responding to toripalimab and after progression the patients also benefits from toripalimab combined with local radiotherapy, which provides a promising option for PSC patients. CONCLUSION: This case provides the evidence of the effective role of toripalimab and PD-1 combined with local radiotherapy in PSC patients, which was the first application as far as we know.

Facile C-N coupling of coordinated ammonia and labile carbonyl or acetonitrile promoted by a thiolate-bridged dicobalt reaction scaffold.

At low temperature, interaction of the thiolate-bridged dicobalt carbonyl complex [Cp*Co(i)(µ-SEt)2(CO)CoCp*][I] (Cp* = η5-C5Me5) (1) with NH3 resulted in the C-N coupling of the coordinated CO and amido group that originate from ammonia activation to afford a dicobalt formylamino complex [Cp*Co(µ-SEt)2(µ-η1:η1-O[double bond, length as m-dash]CNH2)CoCp*][I] (2). Interestingly, at relatively high temperatures, the labile CO ligand was replaced by NH3 to give a thiolate-bridged dicobalt ammonia complex [Cp*Co(i)(µ-SEt)2(NH3)CoCp*][I] (3). Subsequently, in the presence of the dehalogenation reagent AgPF6, the Co2S2 scaffold can simultaneously activate NH3 and MeCN to produce the complex [Cp*Co(MeCN)(µ-SEt)2(NH3)CoCp*][PF6]2 (4). Furthermore, in the presence of NaOEt, the facile occurrence of the intramolecular cyclization led to the formation of acetamidino-bridged dicobalt complex [Cp*Co(µ-SEt)2(µ-η1:η1-NH(CCH3)NH)CoCp*][PF6] (5), which may proceed through the nucleophilic attack of amido from NH3 to coordinated MeCN followed by the hydrogen atom transfer process. In the presence of MeCN, treatment of 5 with HBF4 released the corresponding [MeC(NH2)NH2]BF4; meanwhile, the [Co2S2] core structural scaffold remained. In this Co2S2 reaction system, the cooperative activation effect between the two cobalt centers plays an important role for NH3 activation and functionalization.

Thiolate-Bridged Dicobalt Complexes Bearing Hydrazine, Hydrazido, and Diazenido Ligands: Synthesis, Structural Characterization, and Interconversion.

Synthetic di- or multimetallic complexes bearing NxHy nitrogenous ligands in a sulfur-rich coordination environment have attracted considerable attention due to their importance in evaluating the complex mechanism of biological nitrogen fixation. Herein, we report a series of thiolate-bridged dicobalt NxHy species obtained by treatment of CoIIICoIII precursor with hydrazine and its substituted derivatives at ambient temperature. Remarkably, when the substituent is the cyclohexyl group, the resulting species can interconvert through different pathways. This Co2S2 skeleton provides a new model system for obtaining valuable information about the early N2Hx-bound intermediate species during the catalytic cycle of nitrogenase.

The Combination of Aquilaria sinensis (Lour.) Gilg and Aucklandia costus Falc. Volatile Oils Exerts Antidepressant Effects in a CUMS-Induced Rat Model by Regulating the HPA Axis and Levels of Neurotransmitters.

The Aquilaria sinensis (Lour.) Gilg (CX)-Aucklandia costus Falc. (MX) herbal pair is frequently used in traditional Chinese medicine prescriptions for treating depression. The volatile oil from CX and MX has been shown to have good pharmacological activities on the central nervous system, but its curative effect and mechanism in the treatment of depression are unclear. Therefore, the antidepressant effect of the volatile oil from CX-MX (CMVO) was studied in chronic unpredictable mild stress (CUMS) rats. The suppressive effects of CMVO (25, 50, 100 µL/kg) against CUMS-induced depression-like behavior were evaluated using the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT). The results showed that CMVO exhibited an antidepressant effect, reversed the decreased sugar preference in the SPT and prolongation of immobility time in the FST induced by CUMS, increased the average speed, time to enter the central area, total moving distance, and enhanced the willingness of rats to explore the environment in the OFT. Inhalational administration of CMVO decreased levels of adrenocorticotropic hormone and corticosterone in serum and the expression of corticotropin-releasing hormone mRNA in the hypothalamus, which indicated regulation of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, CMVO restored levels of 5-hydroxytryptamine (5-HT), dopamine, norepinephrine and acetylcholine in the hippocampus. The RT-PCR and immunohistochemistry results showed that CMVO up-regulated the expression of 5-HT1A mRNA. This study demonstrated the antidepressant effect of CMVO in CUMS rats, which was possibly mediated via modulation of monoamine and cholinergic neurotransmitters and regulation of the HPA axis.

Protective effects of paeoniflorin on acrolein-induced apoptosis in H9c2 cardiomyocytes.

Acrolein is a highly toxic unsaturated aldehyde which is abundant in many circumstances. People exposed to acrolein may have significant clinical relevance in human cardiotoxicity situations. Paeoniflorin (PEF) is a bioactive glucoside isolated from the roots of Paeonia lactiflora Pall. It is reported that PEF performs a beneficial role in cardiovascular system. The aim of the current research was to evaluate the potential protective effect of PEF against acrolein-induced apoptotic damage in H9c2 cardiomyocytes. This study revealed that PEF exerted a protective effect on acrolein-induced cardiomyocyte apoptosis. Furthermore, treatment with acrolein could markedly increase the levels of reactive oxygen species (ROS) and expression of cleavage of caspase-9 and caspase-3 in H9c2 cardiomyocytes, which were significantly reversed by co-treatment with PEF (100uM). These results demonstrated that PEF protects H9c2 cardiomyocytes against acrolein-induced cardiomyocyte injury via decreasing ROS production and down regulating caspases cascade reaction, indicating that PEF is a potential therapeutic agent for cardiac toxic environmental pollutant injury.

Base-Controlled Regiodivergent Azidation of Trifluoromethyl Alkenyl Triflates: Transition-Metal-Free Access to CF3-Containing Allyl Azides and Alkenyl Azides.

A base-controlled regiodivergent azidation of trifluoromethyl alkenyl triflates providing either (E)-3-azido-1-aryl-4,4,4-trifluorobut-1-ene (CF3-containing allyl azides) or (Z)-1-azido-1-aryl-4,4,4-trifluorobut-1-ene (CF3-containing alkenyl azides) is described. Catalyzed by Et3N, the azidation of trifluoromethyl alkenyl triflates with TMSN3 gave CF3-containing allyl azides. On the other hand, using stoichiometric DBU, the regioisomeric azidation products, CF3-containing alkenyl azides, were obtained in good yield. A further transformation for CF3-containing amines, triazoles, and azirines highlights the practical applicability of this transition-metal-free protocol.

Migratory insertion and hydrogenation of a bridging azide in a thiolate-bridged dicobalt reaction platform.

A novel well-defined thiolate-bridged dicobalt azido complex is converted to a rare sulfilimide-bridged dicobalt complex via nitrogen atom migratory insertion into the Co-S bond upon thermolysis. Intriguingly, the homolytic cleavage of hydrogen is achieved by this azide under mild conditions to furnish a partially hydrogenated azido complex.

Short-term clinical effect of conformal radiotherapy combined with tegafur gimeracil oteracil potassium in treating recurrent esophagus cancer.

OBJECTIVE: To observe clinical effects of three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy in the treatment of patients with recurrent esophagus cancer. METHODS: One hundred and twelve senile patients who suffered from esophagus cancer were selected and randomly divided into two groups, namely, observation group (56 cases) and control group (56 cases). The observation group adopted three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy and the control group adopted three-dimensional conformal radiotherapy only. RESULTS: All patients completed the treatment, with good compliance. Effective rate of the observation group was 82.1%, which was significantly higher than the control group (67.9%), and the difference was statistically significant (P<0.05). Main toxic and side effects of patients of two groups were radiation esophagitis, gastrointestinal reaction, hematologic toxicities and radiative skin reaction. Differences of incidence rates of all types of toxic and side effects were not statistically significant (P>0.05). The one-year and two-year survival rates of patients of the observation group were 80.4% and 53.6%, respectively, while the control group was 55.4% and 30.4%; differences between two groups were statistically significant (P<0.05). CONCLUSION: Three-dimensional conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy has definite curative effect in treating patients with recurrent esophagus cancer and can improve survival rate of patients, without increasing adverse reaction.

TRIM11, a direct target of miR-24-3p, promotes cell proliferation and inhibits apoptosis in colon cancer.

TRIM11 (tripartite motif-containing protein 11) is an E3 ubiquitin ligase recently identified as an oncogene in malignant glioma and lung cancer. In the present study, we report that expression of TRIM11 was increased in colon cancer (CC) tissue relative to paired normal tissues and that higher TRIM11 levels predicted poor overall survival (OS) and disease-free survival (DFS) in CC patients. Mechanistically, we showed that miR-24-3p downregulation contributes to TRIM11 upregulation in CC. We also demonstrated that TRIM11 overexpression promotes cell proliferation and colony formation and inhibits apoptosis in CC, while knocking down TRIM11 using CRISPR/Cas9-mediated genome editing inhibited cell proliferation and induced apoptosis. Silencing TRIM11 in vivo decreased tumor growth. These findings indicate that TRIM11 facilitates CC progression by promoting cell proliferation and inhibiting apoptosis and that the novel miR-24-3p/TRIM11 axis may be a useful new target for treating patients with CC.

Structural characterization and proton reduction electrocatalysis of thiolate-bridged bimetallic (CoCo and CoFe) complexes.

Using an assembly method, dinuclear CoCo and CoFe complexes supported by a bdt ligand, [Cp*Co(µ-η2:η2-bdt)(µ-I)CoCp*][PF6] (1[PF6], Cp* = η5-C5Me5, bdt = benzene-1,2-dithiolate), and [Cp*Co(µ-η2:η4-bdt)FeCp'][PF6] (3[PF6], Cp' = η5-C5Me4H) were synthesized in high yields. Upon chemical reduction with CoCp2, complexes 1[PF6] and 3[PF6] were converted to [Cp*Co(µ-η2:η2-bdt)CoCp*] (2) and [Cp*Co(µ-η2:η4-bdt)FeCp'][PF6] (3), respectively. Treatment of 2 with HBF4 resulted in the protonation of two cobalt centers to generate a hydride bridged complex, [Cp*Co(µ-η2:η2-bdt)(µ-H)CoCp*][BF4] (4[BF4]), which was identified by spectroscopy and X-ray crystallography. When treating 3 with HBF4, a one-electron oxidation occurred to afford complex 3[BF4] along with the formation of H2. Importantly, heterodinuclear complex 3[PF6] and hydride bridged complex 4[BF4] can serve as effective catalysts to promote proton reduction for hydrogen evolution, as evidenced by cyclic voltammetry.

Biological significance of PinX1 telomerase inhibitor in esophageal carcinoma treatment.

In the present study, to investigate the expression of PinX1 gene and its functional effects in human esophageal carcinoma (Eca)-109 cell line, expression vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM-siRNA) were constructed and transfected into Eca-109 cells using Lipofectamine 2000. Firstly, the mRNA expression level of PinX1 was examined using reverse transcription-polymerase chain reaction (RT-PCR). Once successful transfection was achieved, the effects on the mRNA level of human telomerase reverse transcriptase (hTERT), telomerase activity, cell proliferation and apoptosis were examined by semi-quantitative RT-PCR, stretch PCR, MTT assay and flow cytometry, respectively. Analysis of restriction and sequencing demonstrated that the recombining plasmids were successfully constructed. The results also indicated that transfection with pEGFP-C3-PinX1 and PinX1-FAM-siRNA into Eca-109 cells significantly increased PinX1 mRNA, decreased hTERT mRNA by 29.9% (P<0.05), and significantly reduced telomerase activity (P<0.05), inhibited cell growth, and increased the cell apoptotic index from 19.27±0.76 to 49.73±2%. The transfected PinX1-FAM-SiRNA exhibited PinX1 mRNA expression levels that were significantly decreased by 70% (P<0.05), whereas the remaining characteristics of Eca-109 cells, including cell growth, mRNA level of hTERT, telomerase activity and cell apoptotic index were not altered. Exogenous PinX1 has been demonstrated to be highly expressed in human Eca. PinX1 can inhibit human telomerase activity and the expression of hTERT mRNA, reduce tumor cell growth and induce apoptosis. Notably, these inhibitory functions were inhibited by silencing PinX1 in Eca with PinX1-FAM-siRNA. PinX1 was successfully increased and decreased in the present study, demonstrating that it may be a potential telomerase activity inhibitor. As PinX1 is an endogenous telomerase inhibitor, it may be used as a novel tumor-targeted gene therapy.

Paeoniflorin inhibits doxorubicin-induced cardiomyocyte apoptosis by downregulating microRNA-1 expression.

Doxorubicin (DOX) is an effective anthracycline anti-tumor antibiotic. Because of its cardiotoxicity, the clinical application of DOX is limited. Paeoniflorin (PEF), a monoterpene glucoside extracted from the dry root of Paeonia, is reported to exert multiple beneficial effects on the cardiovascular system. The present study was designed to explore the protective effect of PEF against DOX-induced cardiomyocyte apoptosis and the underlying mechanism. In cultured H9c2 cells, PEF (100 µmol/l) was added for 2 h prior to exposure to DOX (5 µmol/l) for 24 h. Cell viability, creatine kinase activity, cardiomyocyte apoptosis, intracellular reactive oxygen species (ROS) levels, and the expression of microRNA-1 (miR-1) and B-cell lymphoma 2 (Bcl-2) were measured following treatment with PEF and/or DOX. The results showed that treatment with DOX notably induced cardiomyocyte apoptosis, concomitantly with enhanced ROS generation, upregulated miR-1 expression and downregulated Bcl-2 expression. These effects of DOX were significantly inhibited by pretreatment of the cells with PEF. These results suggest that the inhibitory effect of PEF on DOX-induced cardiomyocyte apoptosis may be associated with downregulation of miR-1 expression via a reduction in ROS generation.