Understanding the links between micro/nanoplastics-induced gut microbes dysbiosis and potential diseases in fish: A review.

At present, the quantity of micro/nano plastics in the environment is steadily rising, and their pollution has emerged as a global environmental issue. The tendency of their bioaccumulation in aquatic organisms (especially fish) has intensified people's attention to their persistent ecotoxicology. This review critically studies the accumulation of fish in the intestines of fish through active or passive intake of micro / nano plastics, resulting in their accumulation in intestinal organs and subsequent disturbance of intestinal microflora. The key lies in the complex toxic effect on the host after the disturbance of fish intestinal microflora. In addition, this review pointed out the characteristics of micro / nano plastics and the effects of their combined toxicity with adsorbed pollutants on fish intestinal microorganisms, in order to fully understand the characteristics of micro / nano plastics and emphasize the complex interaction between MNPs and other pollutants. We have an in-depth understanding of MNPs-induced intestinal flora disorders and intestinal dysfunction, affecting the host's systemic system, including immune system, nervous system, and reproductive system. The review also underscores the imperative for future research to investigate the toxic effects of prolonged exposure to MNPs, which are crucial for evaluating the ecological risks posed by MNPs and devising strategies to safeguard aquatic organisms.

Repurposing diacerein to suppress colorectal cancer growth by inhibiting the DCLK1/STAT3 signaling pathway.

Double cortin-like kinase 1 (DCLK1) exhibits high expression levels across various cancers, notably in human colorectal cancer (CRC). Diacerein, a clinically approved interleukin (IL)-1ß inhibitor for osteoarthritis treatment, was evaluated for its impact on CRC proliferation and migration, alongside its underlying mechanisms, through both in vitro and in vivo analyses. The study employed MTT assay, colony formation, wound healing, transwell assays, flow cytometry, and Hoechst 33342 staining to assess cell proliferation, migration, and apoptosis. Additionally, proteome microarray assay and western blotting analyses were conducted to elucidate diacerein's specific mechanism of action. Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo. Through high-throughput proteomics microarray and molecular docking studies, we identified that diacerein directly interacts with DCLK1. Mechanistically, the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed. Furthermore, diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets, including MCL-1, VEGF, and survivin, thereby inhibiting CRC progression in a mouse model, thereby inhibiting CRC progression in a mouse model.

Correlation between RNA N6-methyladenosine and ferroptosis in cancer: current status and prospects.

N6-methyladenosine (m6A) is the most abundant chemical modification in eukaryotic cells. It is a post-transcriptional modification of mRNA, a dynamic reversible process catalyzed by methyltransferase, demethylase, and binding proteins. Ferroptosis, a unique iron-dependent cell death, is regulated by various cell metabolic events, including many disease-related signaling pathways. And different ferroptosis inducers or inhibitors have been identified that can induce or inhibit the onset of ferroptosis through various targets and mechanisms. They have potential clinical value in the treatment of diverse diseases. Until now, it has been shown that in several cancer diseases m6A can be involved in the regulation of ferroptosis, which can impact subsequent treatment. This paper focuses on the concept, function, and biological role of m6A methylation modification and the interaction between m6A and ferroptosis, to provide new therapeutic strategies for treating malignant diseases and protecting the organism by targeting m6A to regulate ferroptosis.

Mining oomycete proteomes for phosphatome leads to the identification of specific expanded phosphatases in oomycetes.

Phosphatases are important regulators of protein phosphorylation and various cellular processes, and they serve as counterparts to kinases. In this study, our comprehensive analysis of oomycete complete proteomes unveiled the presence of approximately 3833 phosphatases, with most species estimated to have between 100 and 300 putative phosphatases. Further investigation of these phosphatases revealed a significant increase in protein serine/threonine phosphatases (PSP) within oomycetes. In particular, we extensively studied the metallo-dependent protein phosphatase (PPM) within the PSP family in the model oomycete Phytophthora sojae. Our results showed notable differences in the expression patterns of PPMs throughout 10 life stages of P. sojae, indicating their vital roles in various stages of oomycete pathogens. Moreover, we identified 29 PPMs in P. sojae, and eight of them possessed accessory domains in addition to phosphate domains. We investigated the biological function of one PPM protein with an extra PH domain (PPM1); this protein exhibited high expression levels in both asexual developmental and infectious stages. Our analysis confirmed that PPM1 is indeed an active protein phosphatase, and its accessory domain does not affect its phosphatase activity. To delve further into its function, we generated knockout mutants of PPM1 and validated its essential roles in mycelial growth, sporangia and oospore production, as well as infectious stages. To the best of our knowledge, this study provides the first comprehensive inventory of phosphatases in oomycetes and identifies an important phosphatase within the expanded serine/threonine phosphatase group in oomycetes.

Facile Preparation of ß-Cyclodextrin-Modified Polysulfone Membrane for Low-Density Lipoprotein Adsorption via Dopamine Self-Assembly and Schiff Base Reaction.

A facile method for the immobilization of ß-cyclodextrin on polysulfone membranes with the aim of selectively adsorbing low-density lipoprotein (LDL) was established, which is based on the self-assembly of dopamine on the membrane followed by the Schiff base reaction with mono-(6-ethanediamine-6-deoxy)-ß-cyclodextrin. The surface modification processes were validated using X-ray photoelectron spectroscopy and attenuated total reflectance Fourier-transform infrared spectroscopy. Surface wettability and surface charge of the membranes were investigated through the water contact angle and zeta potential analysis. The cyclodextrin-modified polysulfone membrane (PSF-CD) showed good resistance to protein solutions, as shown by the measurement of BSA adsorption. The assessment of BSA adsorption revealed that the cyclodextrin-modified polysulfone membrane (PSF-CD) exhibited excellent resistance to protein solutions. To investigate the adsorption and desorption behaviors of the membranes in single-protein or binary-protein solutions, an enzyme-linked immunosorbent assay was employed. The results revealed that the PSF-CD possessed remarkable adsorption capacity and higher affinity for LDL in both single-protein and binary-protein solutions, rendering it a suitable material for LDL apheresis.

Solamargine improves the therapeutic efficacy of anti-PD-L1 in lung adenocarcinoma by inhibiting STAT1 activation.

OBJECTIVE: The effect of solamargine on lung adenocarcinoma and its effect on STAT1 signaling pathway mediated immune escape were studied through network pharmacology and in vitro and in vivo experiments. METHODS: The solamargine targets were screened using the TCMSP and the LUAD targets were screened using the GeneCard, OMIM, PharmGkb, TTD and DrugBank databases. PPI network analysis and target prediction were performed using GO and KEGG. Colony formation assay, EDU staining, wound healing, transwell assay, Hoechst and flow cytometry were used to detect the effects of solamargine on the proliferation, migration and apoptosis of LUAD. Western blotting (WB) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect P-STAT1 and PD-L1 expression. And immunofluorescence was used to detect P-STAT1 expression. In vivo experiments, C57BL/6 mice were divided into control group, low concentration group, high concentration group, positive control group and combination group. Every other day, following seven consecutive doses, the size of the tumor was assessed. Finally, the expressions of P-STAT1, STAT1, PD-L1 and apoptosis index proteins were detected by WB. RESULTS: The anti-LUAD effect of solamargine was found by wound healing, colony formation assay, transwell assay, hoechst and EdU staining. The results of network pharmacological analysis showed that solamargine could suppress STAT1 expression level. Further enrichment assay of STAT1 showed that STAT1 was associated with immune-related pathways. In addition, molecular signal analysis by WB and RT-qPCR indicated that solamargine could reduce the expression levels of P-STAT1 and PD-L1 in a concentration-dependent manner. According to the results of in vivo assays, combination of solamargine and immune checkpoint inhibitors (ICIs) durvalumab could significantly inhibit the growth of Lewis transplanted tumors in C57BL/6 mice, and no toxic side effect was recoded. CONCLUSION: These results indicated that solamargine could inhibit the proliferation and promote the apoptosis of LUAD. It also could reduce the expression level of P-STAT1 protein and inhibit the expression level of PD-L1. At the same time, the combination with the ICIs can better block the expression of PD-L1 in cells, thereby inhibiting the immune escape pathway of tumor cells and achieving anti-tumor effects. This study proposed a novel combined therapeutic approach, involving the inhibition of STAT1 by solamargine in conjunction with ICIs.

Research advances in microfluidic collection and detection of virus, bacterial, and fungal bioaerosols.

Bioaerosols are airborne suspensions of fine solid or liquid particles containing biological substances such as viruses, bacteria, cellular debris, fungal spores, mycelium, and byproducts of microbial metabolism. The global Coronavirus disease 2019 (COVID-19) pandemic and the previous emergence of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza have increased the need for reliable and effective monitoring tools for bioaerosols. Bioaerosol collection and detection have aroused considerable attention. Current bioaerosol sampling and detection techniques suffer from long response time, low sensitivity, and high costs, and these drawbacks have forced the development of novel monitoring strategies. Microfluidic technique is considered a breakthrough for high performance analysis of bioaerosols. In recent years, several emerging methods based on microfluidics have been developed and reported for collection and detection of bioaerosols. The unique advantages of microfluidic technique have enabled the integration of bioaerosol collection and detection, which has a higher efficiency over conventional methods. This review focused on the research progress of bioaerosol collection and detection methods based on microfluidic techniques, with special attention on virus aerosols and bacterial aerosols. Different from the existing reviews, this work took a unique perspective of the targets to be collected and detected in bioaerosols, which would provide a direct index of bioaerosol categories readers may be interested in. We also discussed integrated microfluidic monitoring system for bioaerosols. Additionally, the application of bioaerosol detection in biomedicine was presented. Finally, the current challenges in the field of bioaerosol monitoring are presented and an outlook given of future developments.

Late-stage gem-difluoroallylation of phenol in bioactive molecules and peptides with 3,3-difluoroallyl sulfonium salts.

An efficient method for the late-stage selective O-fluoroalkylation of tyrosine residues with a stable yet highly reactive fluoroalkylating reagent, 3,3-difluoroallyl sulfonium salts (DFASs), has been developed. The reaction proceeds in a mild basic aqueous buffer (pH = 11.6) with high efficiency, high biocompatibility, and excellent regio- and chemoselectivity. Various oligopeptides and phenol-containing bioactive molecules, including carbohydrates and nucleosides, could be selectively O-fluoroalkylated. The added vinyl and other functional groups from DFASs can be valuable linkers for successive modification, significantly expanding the chemical space for further bioconjugation. The synthetic utility of this protocol has been demonstrated by the fluorescently labeled anti-cancer drug and the synthesis of O-link type 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid-tyrosine3-octreotate (DOTA-TATE), showing the prospect of the method in medicinal chemistry and chemical biology.

CDK4/6 inhibitors in lung cancer: current practice and future directions.

Lung cancer is the leading cause of cancer-related deaths worldwide, and ∼85% of lung cancers are classified as nonsmall cell lung cancer (NSCLC). These malignancies can proliferate indefinitely, in part due to dysregulation of the cell cycle and the resulting abnormal cell growth. The specific activation of cyclin-dependent kinases 4 and 6 (CDK4/6) is closely linked to tumour proliferation. Approximately 80% of human tumours exhibit abnormalities in the cyclin D-CDK4/6-INK4-RB pathway. Specifically, CDK4/6 inhibitors either as monotherapy or combination therapy have been investigated in pre-clinical and clinical studies for the treatment of NSCLC, and promising results have been achieved. This review article focuses on research regarding the use of CDK4/6 inhibitors in NSCLC, including the characteristics and mechanisms of action of approved drugs and progress of pre-clinical and clinical research.

Comparative transcriptome profile reveals insight into the antibacterial immunity mechanism of the loach (Misgurnus anguillicaudatus) fed with soybean fermented broth during lipopolysaccharide (LPS) exposure.

Loach (Misgurnus anguillicaudatus) is a common freshwater commercial fish species in China. The meat of this fish is a good source of protein and other nutrients that are needed for human health. Aquaculture challenges such as diseases and pest susceptibility, excessive density, and nutritional deficiency result in low production of loach rather than increased demand. Due to a lack of knowledge about the immune system of loaches, we carried out this study to better understand its antibacterial molecular mechanism. Here, we performed RNA sequencing from liver tissue obtained from soya bean-fermented fed loach after subjecting it to the LPS challenge. The results revealed a total of 18,399 differentially expressed genes (DEGs) in the LPS-treated and control groups. There were 7482 DEGs that were upregulated and 10,917 DEGs were downregulated. The enrichment analysis of DEGs revealed that the majority of DEGs were found to be abundant in the pathways of DNA replication, spliceosome, nucleotide exception repair, cell cycle, and Herpes simplex virus 1 infection. Furthermore, qRT-PCR analysis of 21 selected DEGs demonstrated that the transcriptomic data is extremely reliable. Overall, this study provides insight into the molecular features and control mechanisms of genes that affect loach growth. The availability of this information will also contribute to the enhancement of the breeding and protection of loach resources.

Interface Engineering for Highly Efficient Organic Solar Cells.

Organic solar cells (OSCs) have made dramatic advancements during the past decades owing to the innovative material design and device structure optimization, with power conversion efficiencies surpassing 19% and 20% for single-junction and tandem devices, respectively. Interface engineering, by modifying interface properties between different layers for OSCs, has become a vital part to promote the device efficiency. It is essential to elucidate the intrinsic working mechanism of interface layers, as well as the related physical and chemical processes that manipulate device performance and long-term stability. In this article, the advances in interface engineering aimed to pursue high-performance OSCs are reviewed. The specific functions and corresponding design principles of interface layers are summarized first. Then, the anode interface layer, cathode interface layer in single-junction OSCs, and interconnecting layer of tandem devices are discussed in separate categories, and the interface engineering-related improvements on device efficiency and stability are analyzed. Finally, the challenges and prospects associated with application of interface engineering are discussed with the emphasis on large-area, high-performance, and low-cost device manufacturing.

Acute and chronic toxicity in Sprague-Dawley rats of orally-administered total lignans from Arctii Fructus, a potential therapeutic drug for diabetes.

Arctii Fructus is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is in the Chinese pharmacopoeia. Previous research showed that the total lignans from Arctii Fructus (TLAF) have pharmacological activities related to diabetes. This study evaluated the acute and chronic (26 weeks) toxicities associated with oral daily administration of TLAF in Sprague-Dawley (SD) rats. An acute-toxicity test showed that TLAF caused 10% mortality at 3,000 mg/kg × 2 (6-h interval), with toxic symptoms, such as dyspnea and tonic convulsions, indicating potential neurotoxicity. A chronic-toxicity study showed no mortality after administration. The no observed adverse-effect level was 1,800 mg/kg (approximately 54 times higher than the human clinical dose) for 26 weeks of TLAF oral administration in SD rats, with toxicity signs of excessive oral and nasal secretions and moist circumferential hair that recovered after TLAF discontinuation. In the toxicokinetic study, the two main components of TLAF, arctigenin plasma level was positively correlated with dose and tended to accumulate after multiple doses. At 1,800 mg/kg, arctiin plasma level increased and tended to accumulate after multiple doses. These results indicated that TLFA has relatively low toxicity and the potential for clinical treatment of diabetes.

Advances in NIR-Responsive Natural Macromolecular Hydrogel Assembly Drugs for Cancer Treatment.

Cancer is a serious disease with an abnormal proliferation of organ tissues; it is characterized by malignant infiltration and growth that affects human life. Traditional cancer therapies such as resection, radiotherapy and chemotherapy have a low cure rate and often cause irreversible damage to the body. In recent years, since the traditional treatment of cancer is still very far from perfect, researchers have begun to focus on non-invasive near-infrared (NIR)-responsive natural macromolecular hydrogel assembly drugs (NIR-NMHADs). Due to their unique biocompatibility and extremely high drug encapsulation, coupling with the spatiotemporal controllability of NIR, synergistic photothermal therapy (PTT), photothermal therapy (PDT), chemotherapy (CT) and immunotherapy (IT) has created excellent effects and good prospects for cancer treatment. In addition, some emerging bioengineering technologies can also improve the effectiveness of drug delivery systems. This review will discuss the properties of NIR light, the NIR-functional hydrogels commonly used in current research, the cancer therapy corresponding to the materials encapsulated in them and the bioengineering technology that can assist drug delivery systems. The review provides a constructive reference for the optimization of NIR-NMHAD experimental ideas and its application to human body.

Cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling.

Background: Non-small-cell lung cancer (NSCLC) is the most common histological subtype of lung cancer with significant morbidity and mortality rates worldwide. Cinobufagin, the primary component of Chansu and the major active ingredient of cinobufacini, has attracted widespread attention for its excellent anticancer effects, but its activity remains poorly characterized in NSCLC. Methods: The functions of cinobufagin treatment in anti-tumor was evaluated using various in vitro and in vivo assays. The change of STAT3 signaling by cinobufagin was analyzed using molecular docking, immunofluorescence technic and western blotting. Results: In vitro, we confirmed the inhibitory effect of cinobufagin on cell viability, proliferation, migration, epithelial-mesenchymal transition (EMT), as well as an apoptosis-inducing effect. The antitumor effects of cinobufagin were confirmed in vivo by measuring tumor growth in a mouse xenograft model. Cinobufagin was found to significantly inhibit the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at tyrosine 705 (Y705) in a time- and concentration-dependent manner. Moreover, cinobufagin reversed IL-6-induced nuclear translocation of STAT3. Conclusions: Our study has demonstrated that cinobufagin exerts an antitumor effect in non-small-cell lung cancer by blocking STAT3 signaling, and cinobufagin is a promising candidate agent for NSCLC therapy.

Current situation and trend of translational research of acupuncture-moxibustion in treatment of aphasia based on knowledge graph analysis. / åŸºäºŽçŸ¥è¯†å›¾è°±æŠ€æœ¯åˆ†æžé’ˆç¸æ²»ç–—å¤±è¯­ç—‡è½¬åŒ–ç ”ç©¶çš„çŽ°çŠ¶ä¸Žè¶‹åŠ¿.

OBJECTIVES: To investigate the hot topics in acupuncture-moxibustion research for treatment of aphasia and explore the current situation and trend of technology transformation in this field through analyzing the relevant Chinese literatures in recent 30 years by means of knowledge graph technology. METHODS: CiteSpace 6.1.R 2 and VOSviewer V1.6.16 software were used to collate the data, draw knowledge graphs and conduct visual analysis of the literatures related to acupuncture-moxibustion treatment of aphasia, searched from CNKI, WanFang and VIP databases.The time line view and strongest bursts of keywords were formed in the field of acupuncture-moxibustion treatment for aphasia. The treatment-based keyword networks were visualized. RESULTS: A total of 773 Chinese articles were included. Through visual analysis of the co-occurrence networks, the top 10 high-frequency overall keywords and the top 10 clusters of overall keywords were listed. The top 5 high-frequency aphasia categories were Broca aphasia, hysterical aphasia, transcortical motor aphasia, nominal aphasia and sensory aphasia. Regarding the keywords of the techniques of acupuncture-moxibustion, the occurrence frequencies of scalp acupuncture, tongue acupuncture, body acupuncture and electroacupuncture were ≥ 10 times.The occurrence frequencies of 16 acupoints were ≥25 times. After collation and cluster analysis of acupoints and techniques of acupuncture-moxibustion, 7 keyword clusters of "acupuncture techniques-acupoints" were obtained. The time line view showed that the strongest burst of keywords were transcranial magnatic stimulation, language rehabilitation training, acupuncture-medicine therapy and stroke, etc. in the recent 5 years. CONCLUSIONS: Acupuncture-moxibustion displays its unique advantage in treatment of aphasia. With the deepening of modern research, the hot topics for aphasia treated with acupuncture-moxibustion are present and the achievements enriched. In future, these therapeutic methods should be further investigated to explore a model of translational medicine for aphasia in line with the characteristics of acupuncture-moxibustion.

Molecular cloning and functional characterization of peroxinectin from red swamp crayfish, Procambarus clarkii.

Peroxinectin, which has both peroxidase and cell adhesion activities, is crucial for invertebrate innate immune responses. In this study, we first cloned the full-length cDNA of Procambarus clarkii Peroxinectin (denoted as Pc-Px) and evaluated its immune roles. The Pc-Px cDNA had 2460 base pairs (bp) and 819 amino acid residues, including peroxidase domain and a putative integrin-binding motif. Pc-Px tissue expression was found to be ubiquitous in all examined tissues under normal physiological conditions. Pc-Px mRNA levels were highest in hemocytes, followed by gills and heart, and were lowest in the gut. The LPS, PGN, and Poly I:C treatment significantly up-regulated the transcript level of Pc-Px gene, but the expression trends were different after the microbials component treatments. Pc-Px knockdown using double-stranded RNA altered the transcription profiles of various immune-related genes in hepatopancreas of P. clarkii. Taken together, Pc-Px is an important component of immune system that likely to modulate immune function of P. clarkii via regulating immune-associated genes.

New therapeutic directions in type II diabetes and its complications: mitochondrial dynamics.

As important organelles of energetic and metabolism, changes in the dynamic state of mitochondria affect the homeostasis of cellular metabolism. Mitochondrial dynamics include mitochondrial fusion and mitochondrial fission. The former is coordinated by mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy 1 (Opa1), and the latter is mediated by dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1) and mitochondrial fission factor (MFF). Mitochondrial fusion and fission are generally in dynamic balance and this balance is important to preserve the proper mitochondrial morphology, function and distribution. Diabetic conditions lead to disturbances in mitochondrial dynamics, which in return causes a series of abnormalities in metabolism, including decreased bioenergy production, excessive production of reactive oxygen species (ROS), defective mitophagy and apoptosis, which are ultimately closely linked to multiple chronic complications of diabetes. Multiple researches have shown that the incidence of diabetic complications is connected with increased mitochondrial fission, for example, there is an excessive mitochondrial fission and impaired mitochondrial fusion in diabetic cardiomyocytes, and that the development of cardiac dysfunction induced by diabetes can be attenuated by inhibiting mitochondrial fission. Therefore, targeting the restoration of mitochondrial dynamics would be a promising therapeutic target within type II diabetes (T2D) and its complications. The molecular approaches to mitochondrial dynamics, their impairment in the context of T2D and its complications, and pharmacological approaches targeting mitochondrial dynamics are discussed in this review and promise benefits for the therapy of T2D and its comorbidities.

Sodium nitroprusside alleviates nanoplastics-induced developmental toxicity by suppressing apoptosis, ferroptosis and inflammation.

The health damage caused by nanoplastics (NPs) pollution has become one of the global scientific problems to be solved urgently. However, the toxicological mechanism of NPs is complex, and the research progress of anti-toxicity is limited. Thus, it has potential application value to explore or develop drugs that can effectively alleviate or remove NPs with biological toxicity. In this research, 8 µM sodium nitroprusside (SNP) solution was used to treat zebrafish larvae with 20 mg/L NPs for up to 12 days, and the results showed that SNP treatments were effective in alleviating NPs-caused developmental toxicity in zebrafish larvae. Further examination of its signaling pathway revealed that NPs-induced oxidative stress was mitigated by activating the NO-sGC-cGMP signaling pathway and reduced most of the reactive oxygen species (ROS). Subsequently, we detected the key substances and the key enzymes involved in apoptosis and ferroptosis, and found that oxidative stress-induced mitochondria-dependent apoptosis and lipid peroxidation-caused ferroptosis were alleviated. Finally, observed the accumulation of NPs and ROS in the liver of zebrafish larvae, which is the target organ of immunotoxicity, and we found that SNP could alleviate NPs-caused inflammation by analyzing the fluorescence intensity of neutrophils and macrophages in transgenic zebrafish and detecting the expression of key immune genes. In conclusion, this research has shown for the first time that SNP treatment can significantly inhibit NPs-induced developmental toxicity, resulting from oxidative stress-induced apoptosis, ferroptosis and inflammation in zebrafish larvae.

Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway.

BACKGROUND: The incidence of breast cancer (BC) worldwide has increased substantially in recent years. Epithelial-mesenchymal transition (EMT) refers to a crucial event impacting tumor heterogeneity. Although cinobufagin acts as an effective anticancer agent, the clinical use of cinobufagin is limited due to its strong toxicity. Acetyl-cinobufagin, a pre-drug of cinobufagin, was developed and prepared with greater efficacy and lower toxicity. METHODS: A heterograft mouse model using triple negative breast cancer (TNBC) cell lines, was used to evaluate the potency of acetyl-cinobufagin. Signal transducer and stimulator of transcription 3 (STAT3)/EMT involvement was investigated by gene knockout experiments using siRNA and Western blot analysis. RESULTS: Acetyl-cinobufagin inhibited proliferation, migration, and cell cycle S/G2 transition and promoted apoptosis in TNBC cells in vitro. In general, IL6 triggered the phosphorylation of the transcription factor STAT3 thereby activating the STAT3 pathway and inducing EMT. Mechanistically, acetyl-cinobufagin suppressed the phosphorylation of the transcription factor STAT3 and blocked the interleukin (IL6)-triggered translocation of STAT3 to the cell nucleus. In addition, acetyl-cinobufagin suppressed EMT in TNBC by inhibiting the STAT3 pathway. Experiments in an animal model of breast cancer clearly showed that acetyl-cinobufagin was able to reduce tumor growth. CONCLUSIONS: The findings of this study support the potential clinical use of acetyl-cinobufagin as a STAT3 inhibitor in TNBC adjuvant therapy.

Fabrication and Study of Dextran/Sulfonated Polysulfone Blend Membranes for Low-Density Lipoprotein Adsorption.

The abnormal increase in low-density lipoprotein (LDL) in human blood is a main independent risk factor for the pathogenesis of atherosclerosis, whereas a reduced LDL level effectively lowers morbidity. It is important to develop LDL adsorption materials with high efficiency and selectivity, as well as to simplify their fabrication processes. In this paper, polysulfone (PSF), sulfonated polysulfone (SPSF), and sulfonated polysulfone/dextran (SPSF/GLU) membranes were successfully fabricated for LDL adsorption using a solution casting technique. Attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy measurements confirmed the success of the preparation. The water contact angle decreased from 89.7 ± 3.4° (PSF) to 76.4 ± 3.2° (SPSF) and to 71.2 ± 1.9° (SPSF/GLU), respectively. BSA adsorption testing showed that the SPSF/GLU with surface enrichment of sulfonate groups and glycosyl groups possessed higher resistance to protein solution. The adsorption and desorption behaviors of the studied samples in single-protein or binary-protein solutions were systematically investigated by enzyme-linked immunosorbent assay (ELISA), The results showed that SPSF/GLU, which had excellent resistance to protein adsorption, possessed a similar adsorption capacity to that of PSF. SPSF membrane exhibited excellent selective affinity for LDL in single and binary protein solutions, suggesting potential applications in LDL removal.