LINC00629, a HOXB4-downregulated long noncoding RNA, inhibits glycolysis and ovarian cancer progression by destabilizing c-Myc.

Ovarian cancer (OC) cells typically reprogram their metabolism to promote rapid proliferation. However, the role of long noncoding RNAs (lncRNAs) in the metabolic reprogramming of ovarian cancer, especially in glucose metabolic reprogramming, remains largely unknown. LINC00629 has been reported in our previous study to promote osteosarcoma progression. Upregulated LINC00629 was found to enhance the growth-suppressive effect of apigenin on oral squamous cell carcinoma. However, the precise function of LINC00629 in ovarian cancer development remains poorly understood. In this study, we found that LINC00629 was significantly downregulated in OC tissues and that low LINC00629 expression was associated with poor survival. Inhibition of LINC00629 was required for increased glycolysis activity and cell proliferation in ovarian cancer. In vivo, overexpression of LINC00629 dramatically inhibited tumor growth and lung metastasis. Mechanistically, LINC00629 interacted with and destabilized c-Myc, leading to its ubiquitination and proteasome degradation, further resulting in increased expression of downstream glycolysis-related genes and glucose metabolic reprogramming in OC. Interestingly, HOXB4 bound to the LINC00629 promoter and inhibited its transcription, indicating that LINC00629 is a transcriptional target of HOXB4. Collectively, these findings establish a direct role for LINC00629 in suppressing glucose metabolism, and HOXB4/LINC00629/c-Myc might serve as a potential biomarker and an effective therapeutic strategy for OC cancer treatment.

Application of remimazolam-0.6% sevoflurane anesthesia for flash visual evoked potential monitoring during pituitary adenoma resection: a non-inferiority randomized controlled trial.

BACKGROUND: Flash visual evoked potential (FVEP) is a critical method for monitoring intraoperative visual function during neurosurgery. A new benzodiazepine drug called remimazolam has recently been used for general anesthesia. However, the impact of remimazolam on FVEP remains unclear. Therefore, we aimed to investigate how remimazolam, in comparison to propofol, when combined with 0.6% sevoflurane anesthesia, affects the FVEP waveform during pituitary adenoma resection. METHODS: Overall, 36 patients undergoing pituitary adenoma resection under general anesthesia were randomly assigned to either the remimazolam group (Group R) or the propofol group (Group P) in a prospective, randomized, controlled, non-inferiority trial. For anesthesia induction, a bolus of 0.2 mg/kg remimazolam or 2 mg/kg propofol was intravenously infused for approximately one minute. The anesthesia was maintained by continuous infusion of either remimazolam (0.7-1.0 mg/kg/h) or propofol (4-6 mg/kg/h), in combination with 0.6% sevoflurane, aimed at sustaining the bispectral index (BIS) within the range of 40-60. The primary outcome was the N75-P100 amplitude of FVEP recorded at approximately 20 min after intubation (T0). 10% of the amplitude at T0 in group P was defined as the non-inferiority margin (δ). Confidence interval testing was used to evaluate the non-inferiority hypothesis. The secondary outcomes covered the P100 latency of FVEP, electroretinogram (ERG) b wave amplitude, demographic characteristics, hemodynamics, and occurrence of adverse events. RESULTS: The BIS index during anesthesia was comparable between the groups at the same measured time points (P > 0.05). The N75-P100 amplitude at T0 in group R was 7.64 ± 1.36 µV, while it was 6.96 ± 0.95 µV in group P (P = 0.09), with a mean difference of 0.68 µV (95% CI, -0.11 µV to 1.48 µV). The δ was set at 0.7 and the lower limit of the 95% CI exceeded the -δ. Both remimazolam and propofol had little effect on ERG b-wave amplitudes. At the designated time points, FVEP amplitude and P100 latency displayed no appreciable variation between the two groups (P > 0.05). Furthermore, there were no significant differences in the incidence of adverse events related to anesthesia, needle electrodes, or surgery between the two groups (P > 0.05). CONCLUSION: Our findings suggest that remimazolam-0.6% sevoflurane is non-inferior to propofol-0.6% sevoflurane for general anesthesia, based on the FVEP N75-P100 amplitude. The electrophysiological data obtained in both groups indicate that reproducible and stable FVEP and ERG waveforms can be acquired at set time points. Therefore, for reliable FVEP monitoring, remimazolam-0.6% sevoflurane appears to be a safe and effective protocol in general anesthesia. TRIALS REGISTRATION: This study was registered on chictr.org.cn (ChiCTR2200056803, 17/02/2022).

LBX2-AS1 promotes ovarian cancer progression by facilitating E2F2 gene expression via miR-455-5p and miR-491-5p sponging.

LBX2-AS1 is a long non-coding RNA that facilitates the development of gastrointestinal cancers and lung cancer, but its participation in ovarian cancer development remained uninvestigated. Clinical data retrieved from TCGA ovarian cancer database and the clinography of 60 ovarian cancer patients who received anti-cancer treatment in our facility were analysed. The overall cell growth, colony formation, migration, invasion, apoptosis and tumour formation on nude mice of ovarian cancer cells were evaluated before and after lentiviral-based LBX2-AS1 knockdown. ENCORI platform was used to explore LBX2-AS1-interacting microRNAs and target genes of the candidate microRNAs. Luciferase reporter gene assay and RNA pulldown assay were used to verify the putative miRNA-RNA interactions. Ovarian cancer tissue specimens showed significant higher LBX2-AS1 expression levels that non-cancerous counterparts. High expression level of LBX2-AS1 was significantly associated with reduced overall survival of patients. LBX2-AS1 knockdown significantly down-regulated the cell growth, colony formation, migration, invasion and tumour formation capacity of ovarian cancer cells and increased their apoptosis in vitro. LBX2-AS1 interacts with and thus inhibits the function of miR-455-5p and miR-491-5p, both of which restrained the expression of E2F2 gene in ovarian cancer cells via mRNA targeting. Transfection of miRNA inhibitors of these two miRNAs or forced expression of E2F2 counteracted the effect of LBX2-AS1 knockdown on ovarian cancer cells. LBX2-AS1 was a novel cancer-promoting lncRNA in ovarian cancer. This lncRNA increased the cell growth, survival, migration, invasion and tumour formation of ovarian cancer cells by inhibiting miR-455-5p and miR-491-5p, thus liberating the expression of E2F2 cancer-promoting gene.

Upregulation of bromodomain PHD finger transcription factor in ovarian cancer and its critical role for cancer cell proliferation and survival.

Bromodomain PHD finger transcription factor (BPTF) is a core subunit of the nucleosome-remodeling factor (NURF) complex, which plays an important role in the development of several cancers. However, it is unknown whether BPTF regulates the progression of ovarian cancer (OC). To investigate this, we measured the relative expression levels of BPTF in OC cell lines and tissues using Western blot and immunohistochemistry, respectively, and the results were analyzed using the χ2 test. We also examined the effects from BPTF knockdown on the proliferation, migration, invasiveness, and apoptosis of OC cell lines. Mechanistic studies revealed that these effects were achieved through simultaneous modulation of multiple signaling pathways. We found that BPTF was highly expressed in OC cell lines and tissues compared with a normal human ovarian epithelial cell line and non-cancerous tissues (P < 0.05). These results are also supported by the public RNA-seq data. BPTF overexpression was correlated with a poor prognosis for OC patient survival (P < 0.05). In vitro experiments revealed that the downregulation of BPTF inhibited OC cell proliferation, colony formation, migration, and invasiveness, and induced apoptosis. BPTF knockdown also affected the epithelial-mesenchymal transition (EMT) signaling pathways and induced the cleavage of apoptosis-related proteins. Consequently, BPTF plays a critical role in OC cell survival, and functions as a potential therapeutic target for OC.

Melatonin synergizes BRAF-targeting agent dabrafenib for the treatment of anaplastic thyroid cancer by inhibiting AKT/hTERT signalling.

As a selective inhibitor of BRAF kinase, dabrafenib has shown potent anti-tumour activities in patients with BRAFV600E mutant anaplastic thyroid cancer. However, the resistance of thyroid cancer cells to dabrafenib limited its therapeutic effect. The effects of melatonin and dabrafenib as monotherapy or in combination on the proliferation, cell cycle arrest, apoptosis, migration and invasion of anaplastic thyroid cancer cells were examined. The molecular mechanism involved in drug combinations was also revealed. Melatonin enhanced dabrafenib-mediated inhibition of cell proliferation, migration and invasion, and promoted dabrafenib-induced apoptosis and cell cycle arrest in anaplastic thyroid cancer cells. Molecular mechanistic studies further uncovered that melatonin synergized with dabrafenib to inhibit AKT and EMT signalling pathways. Furthermore, melatonin and dabrafenib synergistically inhibited the expression of hTERT, and the inhibition of cell viability and the induction of cell cycle arrest mediated by the combination of these two drugs were reversed by hTERT overexpression. Taken together, our results demonstrated that melatonin synergized the anti-tumour effect of dabrafenib in human anaplastic thyroid cancer cells by inhibiting multiple signalling pathways, and provided new insights in exploring the potential therapeutic targets for the treatment of anaplastic thyroid cancer.

A comprehensive analysis of IDO1 expression with tumour-infiltrating immune cells and mutation burden in gynaecologic and breast cancers.

Gynaecologic and breast cancers share some similarities at the molecular level. The aims of our study are to highlight the similarities and differences about IDO1, an important immune-related gene in female cancers. The NGS data from TCGA of cervical squamous cell carcinoma (CESC), ovarian serous cystadenocarcinoma (OV), uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS) and breast invasive carcinoma (BRCA) were analysed to identify molecular features, and clinically significant and potential therapeutic targets of IDO1. We found IDO1 was significantly up-regulated in four gynaecologic cancers and breast cancer. According to breast cancer PAM50 classification scheme, IDO1 expression was higher in tumours of basal than other subtypes and showed better survival prognosis in BRCA and OV. Through immune infiltration analysis, we found a strong correlation between IDO1 and immune cell populations especially for dendritic cells and T cells. In addition, we investigated the association between IDO1 and tumour mutation burden (TMB) and found that IDO1 was significantly correlated with TMB in BRCA and CESC. GSVA revealed that hallmarks significantly correlated with IDO1 were involved in interferon gamma response, allograft rejection and inflammatory response. We also found PD-L1 and LAG3 were highly positive related to IDO1 in gynaecologic cancers when comparing with their corresponding normal tissues. Our results indicated that IDO1 participated in anti-tumour immune process and is correlated with mutation burden. These findings may expand our outlook of potential anti-IDO1 treatments.

MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF.

A previous study by our group indicted that overexpression of bromodomain PHD-finger transcription factor (BPTF) occurs in lung adenocarcinoma, and is closely associated with advanced clinical stage, higher numbers of metastatic lymph nodes, the occurrence of distant metastasis, low histological grade, and poor prognosis. Down-regulation of BPTF inhibited lung adenocarcinoma cell proliferation and promoted lung adenocarcinoma cell apoptosis. The purpose of this study is to identify valuable microRNAs (miRNAs) that target BPTF to modulate lung adenocarcinoma cell proliferation. In our results, we found that miR-3666 was notably reduced in lung adenocarcinoma tissues and cell lines. Using an miR-3666 mimic, we discovered that cell proliferation, migration, and invasiveness were suppressed by miR-3666 overexpression, but these were all enhanced when the expression of miR-3666 was reduced. Moreover, bioinformatics analysis using the TargetScan database and miRanda software suggested a putative target site in BPTF 3'-UTR. Furthermore, using a luciferase reporter assay, we verified that miR-3666 directly targets the 3'-UTR of BPTF. Using Western blot we discovered that overexpression of miR-3666 negatively regulates the protein expression of BPTF. Finally, we identified that the PI3K-AKT and epilthelial-mesenchymal transition (EMT) signaling pathways were inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 could play an essential role in cell proliferation, migration, and invasiveness by targeting BPTF and partly inhibiting the PI3K-AKT and EMT signaling pathways in human lung cancers.

MiR-4458 inhibits breast cancer cell growth, migration, and invasiveness by targeting CPSF4.

Numerous studies have reported that CPSF4 is over-expressed in a large percentage of human lung cancers, and CPSF4 has been identified as a potential oncogene of human lung tumor. Downregulation of CPSF4 inhibits the proliferation and promotes the apoptosis of lung adenocarcinoma cells. A previous study by our group also found overexpression of CPSF4 in breast cancer (BC), and was closely associated with a poor prognosis for the patient. This study investigates microRNAs (miRNAs) that target CPSF4 to modulate BC cell proliferation. We found that miR-4458 was noticeably reduced in BC tissues and cells. Using a miR-4458 mimic, we found that cell proliferation, migration, and invasiveness were suppressed by miR-4458 overexpression, and were enhanced by reducing the expression of miR-4458. Moreover, the results from bioinformatics analyses suggest a putative target site in the CPSF4 3'-UTR. Furthermore, using luciferase reporter assays and Western blotting, we verified that miR-4458 directly targets the 3'-UTR of CPSF4 and downregulates COX-2 and h-TERT, which are downstream target genes of CPSF4. Additionally, PI3K/AKT and ERK were shown to be inhibited by miR-4458 overexpression in BC cells. Moreover, miR-4458 suppresses BC cell growth in vivo. Consequently, these results suggest that the miR-4458-CPSF4-COX-2-hTERT axis might serve as a potential target for the treatment of BC patients.

GM13133 is a negative regulator in mouse white adipocytes differentiation and drives the characteristics of brown adipocytes.

Obesity is tightly associated with the disturbance of white adipose tissue storing excess energy. Thermogenic adipocytes (brown and beige) exert a critical role of oxidizing nutrients at the high rates through non-shivering thermogenesis. The recruitment of brown characteristics in white adipocytes, termed browning, has been considered as a promising strategy for treating obesity and associated metabolic complications. Recently, long noncoding RNAs play a crucial role in regulating tissue development and participating in disease pathogenesis, yet their effects on the conversion of white into brown-like adipocytes and thermogenic function were not totally understood. Here, we identified a mouse brown adipose specific expressed lncRNA, termed GM13133. Moreover, a considerable amount of GM13133 is expressed in adipocytes and actively modulated by cold, ß3 -adrenergic agonist and cAMP stimuli, implying a potential role in the conversion from white to brown adipocytes. Overexpression of GM13133 did not affect the proliferation of mouse white pre-adipocytes, but inhibited white adipocyte differentiation by decreasing lipid accumulation. The forced expression of GM13133 also significantly drove the conversion of white into brown-like adipocytes with the enhanced mitochondrial biogenesis and the induced expression of brown adipocytes specific markers. A global mRNA analysis further indicated the possible regulatory role of cAMP signaling pathway in GM13133 mediated white-to-brown adipocytes conversion. Our results identified a lncRNA-mediated modulation in primary mouse white adipocyte differentiation and indicate the functional significance of GM13133 in promoting browning of white adipocytes and maintenance of thermogenesis, further providing a potential strategy to treating obesity.

Identification and characterization of metformin on peptidomic profiling in human visceral adipocytes.

To gain insight into the effect of metformin on losing weight from peptidomic perspective and to screen potential active peptides for reducing fat lipid deposition. After determining the proper concentration of metformin on human primary visceral adipocytes, we constructed a comparative peptidomic profiling between control and metformin treatment group (n = 3) using a stable isobaric labeling strategy involving tandem mass tag reagents, followed by liquid chromatography tandem mass spectrometry. We identified and quantified 3065 non-redundant peptides, 304 of which were differentially expressed after metformin treatment, 206 peptides were up regulated and 98 peptides were down regulated significantly. Gene ontology (GO) enrichment and pathway analysis were performed to study differentially peptides though their precursor proteins. We concluded three peptides located within the functional domains of their precursor proteins could be candidate bioactive peptides for obesity. On one hand, these results confirmed the versatile effects of metformin on adipocyte and advance our current understanding of metformin, on the other hand, these identified peptides might play putative roles in treatment of obesity.

Potential Significance of Peptidome in Human Ovarian Cancer for Patients With Ascites.

OBJECTIVE: Ovarian cancer (OC) is one of the lethal gynecological malignancies. Most women affected by OC with malignant ascites will relapse. Peptidomics, as an emerging branch of proteomics, is more applied in screening of disease biomarkers, diagnosis, treatment, and monitoring. However, there is still little in-depth analysis about peptidomics study in OC with malignant ascites. METHODS: A comparative peptidomic profiling of ascites fluid between 6 OC patients and 6 benign gynecological conditions using liquid chromatography-tandem mass spectrometry was analyzed. Afterward, the Ingenuity Pathway Analysis was performed to reveal the potential function of peptide-protein precursors. RESULTS: A total of 4388 nonredundant peptides were identified, 104 of which were significantly differentially expressed in the ascites fluid of OC and benign gynecological conditions (>2-fold changes and P < 0.05): 52 peptides were upregulated while 52 peptides were downregulated. These peptides were imported into the Ingenuity Pathway Analysis and identified putative roles in OC. CONCLUSIONS: We identified the peptidome patterns of patients with OC and benign gynecological conditions, and these differentially expressed that peptides might play an important role during occurrence and development of OC and will be in hope to explore bioactive peptides in the pathogenesis of OC.

Downregulation of NMI promotes tumor growth and predicts poor prognosis in human lung adenocarcinomas.

BACKGROUND: N-myc (and STAT) interactor (NMI) plays vital roles in tumor growth, progression, and metastasis. In this study, we identified NMI as a potential tumor suppressor in lung cancer and explored its molecular mechanism involved in lung cancer progression. METHODS: Human lung cancer cell lines and a mouse xenograft model was used to study the effect of NMI on tumor growth. The expression of NMI, COX-2 and relevant signaling proteins were examined by Western blot. Tissue microarray immunohistochemical analysis was performed to assess the correlation between NMI and COX-2 expression in lung cancer patients. RESULTS: NMI was highly expressed in normal lung cells and tissues, but lowly expressed in lung cancer cells and tissues. Overexpression of NMI induced apoptosis, suppressed lung cancer cell growth and migration, which were mediated by up-regulation of the cleaved caspase-3/9 and down-regulation of phosphorylated PI3K/AKT, MMP2/MMP9, ß-cadherin, and COX-2/PGE2. In contrast, knockdown of NMI promoted lung cancer cell colony formation and migration, which were correlated with the increased expression of phosphorylated PI3K/AKT, MMP2/MMP9, ß-cadherin and COX-2/PGE2. Further study showed that NMI suppressed COX-2 expression through inhibition of the p50/p65 NF-κB acetylation mediated by p300. The xenograft lung cancer mouse models also confirmed the NMI-mediated suppression of tumor growth by inhibiting COX-2 signaling. Moreover, tissue microarray immunohistochemical analysis of lung adenocarcinomas also demonstrated a negative correlation between NMI and COX-2 expression. Kaplan-Meier analysis indicated that the patients with high level of NMI had a significantly better prognosis. CONCLUSIONS: Our study showed that NMI suppressed tumor growth by inhibiting PI3K/AKT, MMP2/MMP9, COX-2/PGE2 signaling pathways and p300-mediated NF-κB acetylation, and predicted a favorable prognosis in human lung adenocarcinomas, suggesting that NMI was a potential tumor suppressor in lung cancer.

ASS1 Enhances Anoikis Resistance via AMPK/CPT1A-mediated Fatty Acid Metabolism in Ovarian Cancer.

Metastasis is the leading cause of death in ovarian cancer (OC), with anoikis resistance being a crucial step for detached OC cells survival. Despite extensive research, targeting anoikis resistance remians a challenge. Here, we identify argininosuccinate synthase 1 (ASS1), a key enzyme in urea cycle, is markedly upregulated in OC cells in detached culture and is associated with increased anoikis resistance and metastasis. Disruption of the AMP/ATP balance by elevated ASS1 activates AMPK and its downstream factor, CPT1A. Then, ASS1 enhances FAO, leading to higher ATP generation and lipid utilization. Inhibition of CPT1A reverses ASS1-induced FAO. Our study gives some new functional insights into OC metabolism and represents a shift from traditional views, expanding ASS1's relevance beyond nitrogen metabolism to fatty acid metabolism. It uncovers how ASS1-induced FAO disrupts the AMP/ATP balance, leading to AMPK activation. By identifying the ASS1/AMPK/CPT1A axis as crucial for OC anoikis resistance and metastasis, our study opens up new avenues for therapeutic interventions.

Comprehensive Analysis of lncRNA and miRNA Regulatory Network Reveals Potential Prognostic Non-coding RNA Involved in Breast Cancer Progression.

Breast cancer is one of the most common malignant tumors in women and is the second leading cause of cancer deaths among women. The tumorigenesis and progression of breast cancer are not well understood. The existing researches have indicated that non-coding RNAs, which mainly include long non-coding RNA (lncRNA) and microRNA (miRNA), have gradually become important regulators of breast cancer. We aimed to screen the differential expression of miRNA and lncRNA in the different breast cancer stages and identify the key non-coding RNA using TCGA data. Based on series test of cluster (STC) analysis, bioinformatics analysis, and negatively correlated relationships, 122 lncRNAs, 67 miRNAs, and 119 mRNAs were selected to construct the regulatory network of lncRNA and miRNA. It was shown that the miR-93/20b/106a/106b family was at the center of the regulatory network. Furthermore, 6 miRNAs, 10 lncRNAs, and 15 mRNAs were significantly associated with the overall survival (OS, log-rank P < 0.05) of patients with breast cancer. Overexpressed miR-93 in MCF-7 breast cancer cells was associated with suppressed expression of multiple lncRNAs, and these downregulated lncRNAs (MESTIT1, LOC100128164, and DNMBP-AS1) were significantly associated with poor overall survival in breast cancer patients. Therefore, the miR-93/20b/106a/106b family at the core of the regulatory network discovered by our analysis above may be extremely important for the regulation of lncRNA expression and the progression of breast cancer. The identified key miRNA and lncRNA will enhance the understanding of molecular mechanisms of breast cancer progression. Targeting these key non-coding RNA may provide new therapeutic strategies for breast cancer treatment and may prevent the progression of breast cancer from an early stage to an advanced stage.

Highly Efficient Synthesis of Carbon-Based Molybdenum Phosphide Nanoparticles for Electrocatalytic Hydrogen Evolution.

Molybdenum phosphide in transition metal phosphides members are considered as an attractive electrocatalyst for hydrogen evolution reaction (HER). However, its unsatisfactory stability and conductivity in an alkaline environment has dragged on its development. Here, we successfully introduced N, C co-doped MoP (MoP-NC) nanoparticles by a simple and efficient two-step synthesis method using urea as a carbon source into the molybdenum phosphide system. The cheapness of urea and the excellent carbon to nitrogen ratio remove the obstacles ahead of the development of MoP-NC composites. The obtained composites have excellent HER electrocatalytic activity and stability in 1-M potassium hydroxide (KOH) solution, which requires only an overpotential of 131 mV to achieve a current density of 10 mA cm-2 and exhibits negligible performance degradation after 1000 CV cycles.

A novel endogenous antimicrobial peptide CAMP211-225 derived from casein in human milk.

A large number of bioactive peptides derived from breast milk have been identified to be multifunctional having anti-inflammatory, immunoregulatory and antimicrobial activities. Here, we report that an endogenous peptide located at ß-casein 211-225 amino acid from human breast milk (hereafter called CAMP211-225) presents specific antimicrobial activity against pathogenic E. coli and Y. enterocolitica. CAMP211-225 is a novel peptide that occurs at higher levels in preterm milk than in term milk. The minimal inhibitory concentrations (MIC) of CAMP211-225 against E. coli and Y. enterocolitica are 3.125 µg ml-1 and 6.25 µg ml-1, respectively, and the antimicrobial activity of CAMP211-225 was also confirmed by a disk diffusion assay. Further studies using fluorescence staining, scanning electron microscopy and a DNA-binding assay revealed that CAMP211-225 kills bacteria through a membrane-disrupting mechanism, but not by binding to intracellular nucleic acids. Neonatal necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease in neonatal intensive care units. In our study, CAMP211-225 administration effectively reduced ileal mucosa damage in an experimental NEC mice model. These results suggest that the antimicrobial peptide CAMP211-225 may have potential value in the prevention and treatment of neonatal infections.

Elevated MicroRNA-181a-5p Contributes to Trophoblast Dysfunction and Preeclampsia.

OBJECTIVE: It has been demonstrated that preeclampsia is associated with alterations in placental microRNA expression. Previous reports have shown that hsa-miR-181a-5p is overexpressed in human preeclamptic placenta compared with normotensive placenta. The purpose of this study was to explore whether upregulated hsa-miR-181a-5p expression is involved in the ontogenesis of preeclampsia. METHODS: Twenty preeclamptic placentas and 20 normotensive placentas were obtained from nulliparous women by cesarean section. Expression of hsa-miR-181a-5p in placenta tissues and human trophoblast cell lines was analyzed by reverse transcription polymerase chain reaction. The trophoblast cell lines (HTR-8/SVneo and JAR) were transfected with specific oligonucleotides to upregulate miR-181a-5p expression. The effect of miR-181a-5p expression on proliferation, cell cycle, apoptosis, and invasion in HTR-8/SVneo and JAR cells was then investigated. RESULT: It was demonstrated that hsa-miR-181a-5p expression was upregulated in preeclamptic placentas and that it may trigger antiproliferation and inhibition of cell cycle progression, induce apoptosis, and suppress invasion in HTR-8/SVneo and JAR cells. CONCLUSION: Anomalously upregulated hsa-miR-181a-5p expression could contribute to trophoblast dysfunction and may be a crucial factor in the pathogenesis of preeclampsia.

Multifunctional A7R Peptide-Modified Hollow Mesoporous Silica@Ag2S Nanotheranostics for Photoacoustic/Near-Infrared Fluorescence Imaging-Guided Tumor-Targeted Chemo-Photothermal Therapy.

The fabrication of theranostic nanoplatforms which combine diagnostic and therapeutic functions have become an emerging approach for personal nanomedicine. Herein, a multifunctional nanoplatform consisting of A7R peptide (ATWLPPR) conjugated hollow mesoporous silica nanoparticles decorated with Ag2S nanodots (Ag2S@HMSs-A7R) has been developed as an efficient theranostic agent for simultaneous photoacoustic (PA) imaging and near-infrared fluorescence imaging (NIRF)-guided targeted chemotherapy and photothermal therapy against human breast cancer MDA-MB-231 cells. The design of Ag2S doped HMSs by in situ controlled growth of ultrasmall Ag2S nanodots in the mesopores of HMSs. The synthesized multifunctional nanoplatform exhibits high doxorubicin (DOX) loading capability (451 mg/g) and can be precisely controlled by glutathione (GSH), acidic environment and external laser irradiation. Thanks to the strong tunable NIR absorbance of Ag2S, the nanoplatform produce effective photoacoustic capacity and superb photothermal conversion under light irradiation, thereby exhibiting sufficient in vivo fluorescence and photoacoustic signals as well as desirable photothermal therapeutic performance. Importantly, A7R peptide can selectively bind the Neuropilin-1 (NRP-1) receptor which overexpressed by the MDA-MB-231 cells. The achieved Ag2S@HMSs-A7R possess ideal imaging capability for both PA and NIRF imaging in vivo, and the anti-tumor effect of Ag2S@HMSs(DOX)-A7R was studied in vitro and in vivo, showing remarkable synergistic chemo-photothermal effect (combination index, CI < 1). Over all, the strategy of utilizing triple-responsive nanocarriers presents a highly promising potential as an efficient method for cancer theranostics.

A Multifunctional Biodegradable Nanocomposite for Cancer Theranostics.

Theranostic formulations, integrating both diagnostic and therapeutic functions into a single platform, hold great potential for precision medicines. In this work, a biodegradable theranostic based on hollow mesoporous organosilica nanoparticles (HMONs) is reported and explored for ultrasound/photoacoustic dual-modality imaging guided chemo-photothermal therapy of cancer. The HMONs prepared are endowed with glutathione-responsive biodegradation behavior by incorporating disulfide bonds into their framework. The nanoparticles are loaded with indocyanine green (ICG) and perfluoropentane (PFP). The former acts as a photothermal agent and the latter can generate bubbles for ultrasound imaging. A paclitaxel prodrug is developed to both serve as a redox-sensitive gatekeeper controlling ICG release from the HMON pores and a chemotherapeutic. ICG generates mild hyperthermia upon exposure to an 808 nm laser, and this in turn leads to a liquid-gas phase transition of PFP, resulting in the generation of bubbles which can be used for ultrasound imaging. The platform is found to have excellent properties for both ultrasound and photoacoustic imaging. In addition, both in vitro and in vivo results show that the nanoparticles provide potent synergistic chemo-photothermal therapy. The material developed in this work thus has great potential for exploitation in advanced cancer therapies.

GAS5, a FoxO1-actived long noncoding RNA, promotes propofol-induced oral squamous cell carcinoma apoptosis by regulating the miR-1297-GSK3ß axis.

Propofol, an intravenous anaesthetic agent, has been found to exhibit antitumour effects in various kinds of cancer cells. However, the potential roles and regulatory mechanisms of propofol in oral squamous cell carcinoma (OSCC) remain unknown. Herein, we found that propofol inhibits OSCC cell growth and promotes cell apoptosis in a dose- and time-dependent manner. Further mechanistic studies revealed that the long noncoding RNA GAS5 is induced by propofol in OSCC cells. Elevated GAS5 acts as a competing endogenous RNA for miR-1297 and attenuates its inhibitory effect on GSK3ß, leading to GSK3ß increase and Mcl1 decrease. Additionally, we found that FoxO1 binds to the promoter of GAS5, facilitating its transcription in response to propofol treatment. Thus, these results suggest that propofol exhibits antitumour effects in OSCC cells and that the FoxO1-GAS5-miR-1297-GSK3ß axis plays an important role in propofol-induced OSCC cell apoptosis.