MXene-Mediated Catalytic Redox Reactions for Biomedical Applications.

Reactive oxygen species (ROS) play a crucial role in orchestrating a myriad of physiological processes within living systems. With the advent of materdicine, an array of nanomaterials has been intricately engineered to influence the redox equilibrium in biological milieus, thereby pioneering a distinctive therapeutic paradigm predicated on ROS-centric biochemistry. Among these, two-dimensional carbides, nitrides, and carbonitrides, collectively known as MXenes, stand out due to their multi-valent and multi-elemental compositions, large surface area, high conductivity, and pronounced local surface plasmon resonance effects, positioning them as prominent contributors in ROS modulation. This review aims to provide an overview of the advancements in harnessing MXenes for catalytic redox reactions in various biological applications, including tumor, anti-infective, and anti-inflammatory therapies. The emphasis lies on elucidating the therapeutic mechanism of MXenes, involving both pro-oxidation and anti-oxidation processes, underscoring the redox-related therapeutic applications facilitated by self-catalysis, photo-excitation, and sono-excitation properties of MXenes. Furthermore, this review highlights the existing challenges and outlines future development trends in leveraging MXenes for ROS-involving disease treatments, marking a significant step towards the integration of these nanomaterials into clinical practice.

Development of a supportive care needs eHealth application for patients with cervical cancer undergoing surgery: a feasibility study.

PURPOSE: To inform the development of an eHealth application for patients with cervical cancer for monitoring supportive care needs, perceived care supply and quality of life. METHODS: A mixed-method design was used. The 19-month process involved five phases: (1) a literature review to screen the components of applications, (2) a cross-sectional needs assessment for patients with cervical cancer to define the needs and application program frame, (3) expert consultation to refine the draft, (4) software development, and (5) pilot testing and user comment collection. Patients in the intervention group received a 7-day application intervention combined with usual care. Supportive care needs, perceived care supply, quality of life and user's additional comments were collected. RESULTS: The literature review results in phase 1 revealed the importance of full preparation, especially a supportive care needs assessment, before application development. Subsequent supportive care needs investigation in phase 2 revealed that the most urgent needs were informational needs and privacy protection. In phase 3, 43 expert recommendations for application improvement were refined. The new application contained the patient and the health care professional portal in phase 4. Then, on Day 7, there existed score changes of the outcome measures in both intervention and control group. Users had a positive experience with the application. CONCLUSIONS: This study demonstrates the feasibility of applications targeting access to supportive care, which may be effective for improving the outcome measures but needed to be evaluated in future studies.

Masked autoencoders with handcrafted feature predictions: Transformer for weakly supervised esophageal cancer classification.

BACKGROUND AND OBJECTIVE: Esophageal cancer is a serious disease with a high prevalence in Eastern Asia. Histopathology tissue analysis stands as the gold standard in diagnosing esophageal cancer. In recent years, there has been a shift towards digitizing histopathological images into whole slide images (WSIs), progressively integrating them into cancer diagnostics. However, the gigapixel sizes of WSIs present significant storage and processing challenges, and they often lack localized annotations. To address this issue, multi-instance learning (MIL) has been introduced for WSI classification, utilizing weakly supervised learning for diagnosis analysis. By applying the principles of MIL to WSI analysis, it is possible to reduce the workload of pathologists by facilitating the generation of localized annotations. Nevertheless, the approach's effectiveness is hindered by the traditional simple aggregation operation and the domain shift resulting from the prevalent use of convolutional feature extractors pretrained on ImageNet. METHODS: We propose a MIL-based framework for WSI analysis and cancer classification. Concurrently, we introduce employing self-supervised learning, which obviates the need for manual annotation and demonstrates versatility in various tasks, to pretrain feature extractors. This method enhances the extraction of representative features from esophageal WSI for MIL, ensuring more robust and accurate performance. RESULTS: We build a comprehensive dataset of whole esophageal slide images and conduct extensive experiments utilizing this dataset. The performance on our dataset demonstrates the efficiency of our proposed MIL framework and the pretraining process, with our framework outperforming existing methods, achieving an accuracy of 93.07% and AUC (area under the curve) of 95.31%. CONCLUSION: This work proposes an effective MIL method to classify WSI of esophageal cancer. The promising results indicate that our cancer classification framework holds great potential in promoting the automatic whole esophageal slide image analysis.

WS-MTST: Weakly Supervised Multi-Label Brain Tumor Segmentation With Transformers.

Brain tumor segmentation is a key step in brain cancer diagnosis. Segmentation of brain tumor sub-regions, including necrotic, enhancing, and edematous regions, can provide more detailed guidance for clinical diagnosis. Weakly supervised brain tumor segmentation methods have received much attention because they do not require time-consuming pixel-level annotations. However, existing weakly supervised methods focus on the segmentation of the entire tumor region while ignoring the challenging task of multi-label segmentation for the tumor sub-regions. In this article, we propose a weakly supervised approach to solve the multi-label brain tumor segmentation problem. To the best of our knowledge, it's the first end-to-end multi-label weakly supervised segmentation model applied to brain tumor segmentation. With well-designed loss functions and a contrastive learning pre-training process, our proposed Transformer-based segmentation method (WS-MTST) has the ability to perform segmentation of brain tumor sub-regions. We conduct comprehensive experiments and demonstrate that our method reaches the state-of-the-art on the popular brain tumor dataset BraTS (from 2018 to 2020).

Engineering 2D Multienzyme-Mimicking Pyroptosis Inducers for Ultrasound-Augmented Catalytic Tumor Nanotherapy.

Overcoming apoptosis resistance is necessary to ensure an effective cancer treatment; however, it is currently very difficult to achieve. A desirable alternative for cancer treatment is the targeted activation of pyroptosis, a unique type of programmed cell death. However, the pyroptosis inducers that are efficient for cancer therapy are limited. This work reports the engineering of 2D NiCoOx nanosheets as inducers of the production of harmful reactive oxygen species (ROS), which promote intense cell pyroptosis, and that can be applied to ultrasound (US)-augmented catalytic tumor nanotherapy. The main therapeutic task is carried out by the 2D NiCoOx nanosheets, which have four multienzyme-mimicking activities: peroxidase- (POD), oxidase- (OXD), glutathione peroxidase- (GPx), and catalase- (CAT) mimicking activities. These activities induce the reversal of the hypoxic microenvironment, endogenous glutathione depletion, and a continuous ROS output. The ROS-induced pyroptosis process is carried out via the ROS-NLRP3-GSDMD pathway, and the exogenous US activation boosts the multienzyme-mimicking activities and favors the incremental ROS generation, thus inducing mitochondrial dysfunction. The anti-cancer experimental results support the dominance of NiCoOx nanosheet-induced pyroptosis. This work expands on the biomedical applications of engineering 2D materials for US-augmented catalytic breast cancer nanotherapy and deepens the understanding of the multienzyme activities of nanomaterials.

Photo-/piezo-activated ultrathin molybdenum disulfide nanomedicine for synergistic tumor therapy.

Molybdenum disulfide (MoS2), as a transition metal dichalcogenide, has attracted tremendous attention owing to its remarkable electronic, physical, and chemical properties. In this study, based on the energy-converting nanomedicine, we report multifunctional two-dimensional (2D) MoS2 nanosheets with inherent plasmonic property and piezocatalytic activity for imaging-guided synergistic tumor therapy. MoS2 nanosheets display strong plasmon resonances in the near-infrared (NIR) region, especially in the second NIR biological window, possessing a notable light energy to heat effect under 1064 nm laser irradiation, which not only serves as a robust photothermal agent for cancer cell ablation but also acts as a contrast-enhanced agent for thermal imaging and photoacoustic imaging. Meanwhile, MoS2 nanosheets feature a remarkable piezotronic effect, exhibiting mechanical vibration energy to electricity under the stimulation of ultrasound-mediated microscopic pressure for reactive oxygen species generation to further kill cancer cells. The new function for old materials may open up the in-depth exploration of MoS2-based functional biomaterials in the future clinical application of imaging-guided photothermal and piezocatalytic synergetic treatment.

A Sonication-Activated Valence-Variable Sono-Sensitizer/Catalyst for Autography Inhibition/Ferroptosis-Induced Tumor Nanotherapy.

The effective deployment of reactive oxygen species (ROS)-mediated oncotherapy in practice remains challenging, mired by uncontrollable catalytic processes, stern reaction conditions and safety concerns. Herein, we develop a copper nanodot integrating sonodynamic and catalytic effects within one active center, which responds to exogenous ultrasound (US) and endogenous H2 O2 stimuli. US irradiation induces the valence conversion from CuII to CuI catalyzing H2 O2 into ⋅OH for chemodynamic therapy. Meanwhile, valence transformation results in electron-hole pairs separation, promoting ROS generation for sonodynamic therapy. Notably, copper nanodots not only block lysosome fusion and degradation leading to autophagy flux blockage, but also interfere with the glutathione peroxidase 4 and cystine-glutamate antiporter SLC7A11 function achieving ferroptosis. Furthermore, reversible valence changes, inherent hydrophilicity and renal clearance ultrasmall size guarantee biosafety.

Global food insecurity and famine from reduced crop, marine fishery and livestock production due to climate disruption from nuclear war soot injection.

Atmospheric soot loadings from nuclear weapon detonation would cause disruptions to the Earth's climate, limiting terrestrial and aquatic food production. Here, we use climate, crop and fishery models to estimate the impacts arising from six scenarios of stratospheric soot injection, predicting the total food calories available in each nation post-war after stored food is consumed. In quantifying impacts away from target areas, we demonstrate that soot injections larger than 5 Tg would lead to mass food shortages, and livestock and aquatic food production would be unable to compensate for reduced crop output, in almost all countries. Adaptation measures such as food waste reduction would have limited impact on increasing available calories. We estimate more than 2 billion people could die from nuclear war between India and Pakistan, and more than 5 billion could die from a war between the United States and Russia-underlining the importance of global cooperation in preventing nuclear war.

Retropharyngeal Lymph Node Metastasis Diagnosed by Magnetic Resonance Imaging in Hypopharyngeal Carcinoma: A Retrospective Analysis From Chinese Multi-Center Data.

BACKGROUND: To assess the prevalence, risk factors and prognostic significance of retropharyngeal lymph node (RPLN) metastasis diagnosed by magnetic resonance imaging (MRI) in patients with hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: 259 patients from three cancer institutions in China from Jan 2010 to Dec 2018 were analyzed, retrospectively. All the patients had been given pre-treatment magnetic resonance imaging (MRI) of head and neck and were then treated with definitive radiotherapy with or without chemotherapy. Pretreatment diagnostic MRIs were reviewed by a dedicated head and neck radiologist, for the presence or absence of radiographically positive RPLN, cervical LN and tumor invasion.Demographic variables were analysed by descriptive statistics using SPSS 20.0. Predictors of the presence of RPLN and its prognostic significance were examined. RESULTS: RPLN metastasis was discovered in 44 patients (17%). Logistic analysis showed that posterior pharyngeal wall (PPW) primary tumor; PPW invasion; N2-3; multiple cervical lymph node (LN) involvement (>2 LNs) were associated with RPLN metastasis, with metastasis rates 37%, 30%, 31% and 33% respectively. Patients with RPLN metastasis had a significantly reduced 5-year overall survival (OS) and disease-free survival (DFS) compared to the non-RPLN metastasis group (OS 28% vs. 48%, p=0.001; DFS 25% vs. 41%, p=0.040). CONCLUSIONS: RPLN metastasis was not uncommon in HPSCC patients. Risk factors were: PPW primary tumor, PPW invasion and cervical LN status. RPLN metastasis is a poor prognosticator for survival.

Evaluation of a quick one-step sample preparation method for the determination of the isotopic fingerprint of rapeseed (Brassica napus): Investigation of the influence of the use of 2,2-dimethoxypropane on compound-specific stable carbon and hydrogen isotope analyses by gas chromatography combustion/pyrolysis isotope ratio mass spectrometry.

RATIONALE: Gas chromatographic analyses for vegetable oils require transesterification, which generally involves multiple steps, mainly to generate fatty acid methyl esters (FAMEs). A quick method based on acid-catalyzed transesterification using 2,2-dimethoxypropane (DMP) enables the conversion in one step, in a single reactor. For compound-specific stable carbon and hydrogen isotope analyses (C- and H-CSIA) of individual fatty acids (FAs) in oil, the verification of this one-step method has not yet been reported. METHODS: In this study, we evaluated the feasibility of the one-step method for C- and H-CSIA of individual FAMEs in rapeseed samples. The focus was on the investigation of the influence of methanol, which was produced from the reactions of DMP with glycerol and water during transesterification, on the accuracy of isotope composition of FAMEs, consequently of the FAs. The reproducibility of the one-step method was assessed by the measurement of the FAMEs from rapeseed and rapeseed oil. For the C- and H-CSIA of individual FAMEs, a gas chromatography combustion/pyrolysis isotope ratio mass spectrometry system was used. RESULTS: Our results showed that no significant differences arise in the carbon and hydrogen isotope compositions of the selected main FAMEs produced with and without DMP except for the H-CSIA value of C18:3. The reproducibility of the one-step method for rapeseed was in the range of ±0.1 mUr to ± 0.3 mUr for C-CSIA and ±1 mUr to ±3 mUr for H-CSIA of the main FAMEs. CONCLUSIONS: DMP improves the transesterification efficiency without influencing the accuracy of the C- and H-CSIA of FAMEs. The performance of the one-step method for rapeseed samples for the determination of C- and H-CSIA values of FAMEs is satisfactory. Thus, the applicability of the one-step method for isotopic fingerprint analyses of FAs in oilseeds is reported for the first time.

CircCDKN2B-AS1 interacts with IMP3 to stabilize hexokinase 2 mRNA and facilitate cervical squamous cell carcinoma aerobic glycolysis progression.

BACKGROUND: Circular RNAs (circRNAs) have been reported to play key roles in the development of various cancers. However, the biological functions and clinical significance of most circRNAs are still elusive. The purpose of this study was to explore the function and mechanism of a certain circRNA named circCDKN2B-AS1 in cervical cancer development and its potential value in the clinic. METHODS: qRT-PCR was used to verify the expression level of circCDKN2B-AS1. CCK-8, Transwell, and flow cytometry (FCM) assays were performed to detect cellular proliferation, migration, and apoptosis, respectively. A Seahorse XFe96 Analyzer was used to measure glycolysis metabolism level. RNA pull-down, RNA immunoprecipitation (RIP), actinomycin-D addition assays and Western blotting were used to screen and elucidate the potential mechanisms involved. BALB/c nude mice and zebrafish embryos (AB, WT) were used as animal models to investigate tumorigenesis capability. 18FDG-microPET/CT imaging and lactic acid (LA) and pyruvic acid (PA) content detection assays were used to detect the level of glucose metabolism in subcutaneous tumors from nude mice. RESULTS: CircCDKN2B-AS1, a circular isoform of the long noncoding RNA (lncRNA) CDKN2B-AS1, was upregulated in cervical cancer and precancerous tissues. We found that circCDKN2B-AS1 associated with the IMP3 protein depending on a specific binding site and regulated the stability of Hexokinase 2 (HK2) mRNA, the rate-limiting enzyme of the aerobic glycolysis pathway. The expression level of circCDKN2B-AS1 fated the binding of IMP3 to the 3' untranslated region (UTR) of HK2 mRNA, consequently affecting the malignant cell phenotype and aerobic glycolysis in cervical cancer in vitro and in vivo. Mutant circCDKN2B-AS1, lacking the IMP3 binding site, did not have such effects. Utilization of an inhibitory peptide to block the interaction between circCDKN2B-AS1 and the IMP3 protein impeded the binding of IMP3 to the 3'UTR of HK2 mRNA and suppressed aerobic glycolysis in cervical cancer cells. CONCLUSIONS: Our findings demonstrate that circCDKN2B-AS1 facilitates aerobic glycolysis by sponging the IMP3 protein to stabilize HK2 mRNA, consequently promoting the malignant phenotype in cervical cancer, which may provide a potential approach for cervical cancer therapeutics.

The improved targeting of an aspirin prodrug albumin-based nanosystem for visualizing and inhibiting lung metastasis of breast cancer.

Lung metastasis is the principal reason for the majority of deaths from breast cancer. The nonsteroidal anti-inflammatory drug aspirin can prevent lung metastasis in breast tumors via inhibiting heparanase. However, the lack of specific targets and limited accumulation at the site of the tumor have thus far hindered the use of aspirin in oncotherapy. In this study, we developed the nanoplatform FA-BSA@DA and loaded it with the versatile aspirin prodrug DA to visualize and inhibit breast cancer metastasis via targeting heparanase. This nanosystem can be effectively targeted to folic acid (FA)-positive tumor cells, and would then subsequently release a high dose of DA, whose ester bond is specifically ruptured by H2O2 in the tumor microenvironment to afford the therapeutic drug aspirin and near-infrared (NIR) fluorescent reporter DCM. The released aspirin can effectively prevent breast cancer lung metastasis through the inhibition of heparanase activity, and the NIR fluorescent signals emitted from DCM can be used to monitor and evaluate the metastasis levels of breast cancer. Our results showed that the expression of heparanase was significantly decreased, and lung metastasis from breast cancer was effectively monitored and inhibited after treatment with FA-BSA@DA. Furthermore, the collaborative therapy nanoplatform FA-BSA@DA/DOX exhibited strong therapeutic effects in the treatment of breast cancer in vitro and in vivo via the introduction of doxorubicin (DOX) to the system, which resulted in an even stronger result due to its synergistic effects with aspirin. This heparanase-reliant strategy has profound significance for the extended development of nanoplatforms based on versatile aspirin prodrugs, which may offer a solution to clinically prevent breast cancer recurrence and lung metastasis.

A FRET-based upconversion nanoprobe assembled with an electrochromic chromophore for sensitive detection of hydrogen sulfide in vitro and in vivo.

Hydrogen sulfide (H2S) as an important gaseous signaling molecule is closely related to numerous biological processes in living systems. To further study the physiological and pathological roles of H2S, convenient and efficient detection techniques for endogenous H2S in vivo are still in urgent demand. In this study, an electrochromic chromophore, dicationic 1,1,4,4-tetra-aryl butadiene (EM1), was innovatively introduced into upconversion nanoparticles (UCNPs) and a nanoprobe, PAAO-UCNPs-EM1, was constructed for the detection of H2S. This nanosystem was made of core-shell upconversion nanoparticles (NaYF4:Yb,Tm@NaYF4:Yb,Er), EM1, and polyacrylic acid (PAA)-octylamine. The EM1 with strong absorption ranging from 500 to 850 nm could serve as an energy acceptor to quench the upconversion luminescence of UCNPs through the Förster resonance energy transfer (FRET) process. In the presence of H2S, the EM1 in the nanoprobe was reduced to a colorless diene (EM2), resulting in the linear enhancement of luminescence emissions at 660 nm and 800 nm under the excitation of 980 nm light because the FRET was switched off. The nanoprobe PAAO-UCNPs-EM1PAAO-UCNPs-EM1 exhibited fast response and high sensitivity to H2S with a LoD of 1.21 × 10-7 M. Moreover, it was successfully employed in detecting the endogenous and exogenous H2S in living cells with high selectivity and low cytotoxicity. Also, this nanoprobe could distinguish normal and tumor cells by an upconversion luminescence imaging of endogenous H2S. Furthermore, the nanoprobe could significantly monitor H2S in a tumor-bearing nude mouse model. Therefore, we anticipate that this novel nanoprobe assembled with an electrochromic chromophore for responding to H2S and for bioimaging this molecule would have a promising prospect in biological and clinical investigations.

Uterine fibroids may play a protecting role against endometrial carcinoma in Chinese women with gynecological diseases.

BACKGROUND: It has been reported that uterine fibroids (UFs) may increase the risk of endometrial carcinoma (EC) with the underlying mechanism largely unknown. Here, we explore whether UF could be an influential factor for EC. METHODS: We have collected and analyzed clinical data from 4537 Chinese patients to study the co-incidence of UF and EC. Then, a large-scale literature-based data mining was conducted to identify genes implicated as UF downstream regulating targets and EC upstream regulators. In addition, a meta-analysis has been conducted for each of the EC-specific genes, using six independent UF expression datasets. The meta-analysis results, together with literature-based pathway analysis, were used to explore the potential explanation of the clinical data. RESULTS: Our results showed that the incidence rate of EC in the case of UF was 50.53% lower than without UF, which suggested a protective role of UF in EC patients. The meta-analysis identified three significantly overexpressed genes (HTRA3, HOPX, and PCNA) in the case of UF, which were implicated as EC inhibitors in the pathway analysis. Multiple linear regression (MLR) analysis showed that, compared with UF, aging might be a stronger influential factor for EC. CONCLUSION: Among women with gynecological diseases, UFs may play a protecting role against EC in the Chinese population.

Microenvironment remodeled by tumor and stromal cells elevates fibroblast-derived COL1A1 and facilitates ovarian cancer metastasis.

Wide peritoneal metastasis is the cause of the highest lethality of ovarian cancer in gynecologic malignancies. Ascites play a key role in ovarian cancer metastasis, but involved mechanism is uncertain. Here, we performed a quantitative proteomics of ascites, and found that collagen type I alpha 1 (COL1A1) was notably elevated in ascites from epithelial ovarian cancer patients compared to normal peritoneal fluids, and verified that elevated COL1A1 was mainly originated from fibroblasts. COL1A1 promoted migration and invasion of ovarian cancer cells, but such effects were partially eliminated by COL1A1 antibodies. Intraperitoneally injected COL1A1 accelerated intraperitoneal metastasis of ovarian cancer xenograft in NOD/SCID mice. Further, COL1A1 activated downstream AKT phosphorylation by binding to membrane surface receptor integrin ß1 (ITGB1). Knockdown or blockage of ITGB1 reversed COL1A1 enhanced migration and invasion in ovarian cancer cells. Conversely, ovarian cancer ascites and fibrinogen promoted fibroblasts to secrete COL1A1. Elevated fibrinogen in ascites might be associated with increased vascular permeability induced by ovarian cancer. Our findings suggest that microenvironment remodeled by tumor cells and stromal cells promotes fibroblasts to secrete COL1A1 and facilitates the metastasis of ovarian cancer, which may provide a new approach for ovarian cancer therapeutics.

A novel highly selective fluorescent probe with new chalcone fluorophore for monitoring and imaging endogenous peroxynitrite in living cells and drug-damaged liver tissue.

As a member of the reactive nitrogen species (RNS) family, peroxynitrite (ONOO-) as an oxidant and nitrating mediator plays a significant role in some physiopathologic processes. The excessive production of peroxynitrite anion in a drug-damaged liver is a culprit of hepatotoxicity. The detection of peroxynitrite is of vital importance for the treatment of some diseases including cancer and liver injury. In this study, a novel turn-on fluorescent probe IC-ONOO with new chalcone fluorophore was designed and synthesized for the detection of in vitro and in vivo. The probe responded rapidly towards ONOO- (only within 15 min did the fluorescent intensity maximize), and was endowed with high sensitivity and excellent selectivity. Given the fact that the linear correlation between the fluorescent intensity at 560 nm and the concentrations of the probe ranged from 0 to 9 µM, the limit of detection (LOD) was calculated to be 3.1 × 10-8 M. With all the merits, probe IC-ONOO was qualified as a robust tool to monitor peroxynitrite anion under physiopathologic condition. Moreover, it was successfully applied in the imaging of endogenous peroxynitrite in living MCF-7 cells (Human breast carcinoma cells) and mouse drug-damaged liver tissue with low cytotoxicity. Given all the extraordinary merits, great potential has been seen in its application to other peroxynitrite related diseases.

CNN3 acts as a potential oncogene in cervical cancer by affecting RPLP1 mRNA expression.

The prognosis of advanced stage cervical cancer is poorer due to cancer invasion and metastasis. Exploring new factors and signalling pathways associated with invasiveness and metastasis would help to identify new therapeutic targets for advanced cervical cancer. We searched the cancer microarray database, Oncomine, and found elevated calponin 3 (CNN3) mRNA expression in cervical cancer tissues. QRT-PCR verified the increased CNN3 expression in cervical cancer compared to para-cancer tissues. Proliferation, migration and invasion assays showed that overexpressed CNN3 promoted the viability and motility of cervical cancer cells, the opposite was observed in CNN3-knockdown cells. In addition, xenografted tumours, established from SiHa cells with CNN3 knockdown, displayed decreased growth and metastasis in vivo. Furthermore, RNA-sequencing showed that ribosomal protein lateral stalk subunit P1 (RPLP1) was a potential downstream gene. Gene function experiments revealed that RPLP1 had the same biological effects as CNN3 did. Rescue experiments demonstrated that the phenotypes inhibited by CNN3 silencing were partly or completely reversed by RPLP1 overexpression. In conclusion, we verified that CNN3 acts as an oncogene to promote the viability and motility of cervical cancer cells in vitro and accelerate the growth and metastasis of xenografted tumours in vivo, by affecting RPLP1 expression.

SURF4 maintains stem-like properties via BIRC3 in ovarian cancer cells.

OBJECTIVE: As cancer stem cells (CSCs) are considered as the origin of tumor development, recurrence, and drug resistance, we aimed to explore the mechanism related to modulating stemness in CSCs, thus facilitating to search for new therapeutic strategy for ovarian cancer. METHODS: In this study, ovarian cancer stem cells (OCSCs) induced from cell line 3AO and A2780 were enriched in serum-free medium (SFM). The effect of SURF4 on CSC-like properties was evaluated by sphere-forming assays, re-differentiation assays, quantitative real-time polymerase chain reaction, flow cytometry, Western blotting, cell viability assays and in vivo xenograft experiments. The downstream molecule participating in SURF4 maintaining stemness was screened by RNA-sequencing and identified by the experiments of gene function. RESULTS: SURF4 was upregulated expressed in OCSCs. Knockdown of SURF4 reduced the expression of the related stem markers (SOX2 and c-MYC), inhibited self-renewal ability, and improved the sensitivity to chemotherapeutic drugs (paclitaxel and cisplatin) in OCSCs. SURF4 knockdown also inhibited tumorigenesis in nonobese diabetic/severe combined immunodeficiency mice. BIRC3 expression was controlled by SURF4, and BIRC3 showed the similar effect as SURF4 did, and BIRC3 overexpression partially recovered stem-like properties abolished by SURF4 knockdown. CONCLUSION: Our findings suggest that SURF4 possesses the ability to maintain stemness of OCSCs via BIRC3, and may serve as a potential target in stem cell-targeted therapy for ovarian cancer.

Long noncoding RNA GAS5 inhibits cell proliferation and fibrosis in diabetic nephropathy by sponging miR-221 and modulating SIRT1 expression.

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal diseases worldwide. This study is designed to investigate the underlying function and mechanism of a novel lncRNA GAS5 in the progression of DN. We found that lncRNA GAS5 expression level was decreased in type 2 diabetes (T2D) with DN compared with that in patients without DN. Moreover, lncRNA GAS5 expression level was negatively associated with the severity of DN-related complications. lncRNA GAS5 inhibited MCs proliferation and caused G0/1 phase arrest. lncRNA GAS5 overexpression alleviated the expression of fibrosis-related protein in mesangial cells (MCs). The dual-luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay results revealed that lncRNA GAS5 functions as an endogenous sponge for miR-221 via both the directly targeting way and Ago2-dependent manner. Furthermore, SIRT1 was confirmed as a target gene of miR-221. lncRNA GAS5 upregulated SIRT1 expression and inhibited MCs proliferation and fibrosis by acting as an miR-221 sponge. Finally, we found that lncRNA GSA5 suppressed the development of DN in vivo. Thus, lncRNA GAS5 was involved in the progression of DN by sponging miR-221 and contributed to lncRNA-directed diagnostics and therapeutics in DN.

A selective fluorescent turn-on probe for imaging peroxynitrite in living cells and drug-damaged liver tissues.

Peroxynitrite anion (ONOO-), one of the reactive nitrogen species (RNS), plays momentous roles in physiological and pathological processes especially in a range of oxidative stress-related diseases. Moreover, abundant ONOO- is generated in the liver tissues of drug-induced liver injury. We report herein a novel small molecule fluorescent probe KC-ONOO for monitoring ONOO- based on boronate. The probe displayed high sensitivity and good selectivity towards ONOO-. A good linear relationship was observed between the fluorescent intensity at 530 nm and the concentration of ONOO- ranged 0-10 µM with a detection limit of 1.5 × 10-8 M. Furthermore, our probe was successfully applied for imaging ONOO- in living cells and drug-damaged liver tissues with low cytotoxicity, demonstrating the probe KC-ONOO has great potential to further elucidate more biological roles of ONOO-.