Here we report a concise and divergent synthesis of scabrolide A and havellockate, representative members of polycyclic marine natural product furano(nor)cembranoids. The synthesis features a highly efficient exo-exo-endo radical cascade. Through the generation of two rings, three C-C bonds, and three contiguous stereocenters in one step, this remarkable transformation not only assembles the bowl-shaped, common 6-5-5 fused ring system from simple building blocks but also precisely installs the functionalities at desired positions and sets the stage for further divergent preparation of both target molecules. Further studies reveal that the robust and unusual 6-endo radical addition in the cascade is likely facilitated by the rigidity of the substrate.
OBJECTIVES: To assess the safety and efficacy of the combination of brachial artery (BA) cutdown with purse-string suture (PSS) for BA preclosure during fenestrated thoracic endovascular aortic repair (f-TEVAR). METHODS: We reviewed the consecutive data in our center from January 2022 to May 2023. Clinical data were analyzed retrospectively, including the baseline characteristics, procedural details, complications, and outcomes. Dichotomous data were summarized as absolute values and percentages. Continuous variables were presented as median values and interquartile ranges (IQRs). All patients underwent arterial cutdown with the PSS technique for BA preclosure. The technique was considered successful when complete hemostasis was achieved and confirmed by ultrasonography 24 h postoperatively. The patients were followed up 30 days postoperatively for access-related complications. RESULTS: Forty-eight patients who underwent f-TEVAR with 48 BA access sites were included [36 males and 12 females; median age: 62 (IQR: 30-78) years]. The median body mass index was 27.3 (IQR: 21.2-32.7) kg/m2. The median access establishing and closing times were 7.8 (IQR: 6-9.3) min and 3.7 (IQR: 2.5-5) min, respectively. The median operative time and length of stay were 75 (IQR: 63-87) min and 7 (IQR: 5-9) days, respectively. Although the success rate was 100%, partial numbness in the median nerve distribution was noted in 1 patient in the forearm. This resolved spontaneously and no permanent neurological problem was seen. No other access-related complications were noted, and the total complication rate was 2.1% (1/48). CONCLUSIONS: BA preclosure with the PSS technique is safe and effective for left subclavian artery revascularization in Stanford B aortic dissection and can be another option for access closure during f-TEVAR.
Background: Epidemiological research has demonstrated that there is a connection between lipid metabolism disorder and an increased risk of developing arteriosclerosis (AS) and abdominal aortic aneurysm (AAA). However, the precise relationship between lipid metabolism, AS, and AAA is still not fully understood. The objective of this study was to examine the pathways and potential fatty acid metabolism-related genes (FRGs) that are shared between AS and AAA. Methods: AS- and AAA-associated datasets were retrieved from the Gene Expression Omnibus (GEO) database, and the limma package was utilized to identify differentially expressed FRGs (DFRGs) common to both AS and AAA patients. Functional enrichment analysis was conducted on the (DFRGs), and a protein-protein interaction (PPI) network was established. The selection of signature genes was performed through the utilization of least absolute shrinkage and selection operator (LASSO) regression and random forest (RF). Subsequently, a nomogram was developed using the results of the screening process, and the crucial genes were validated in two separate external datasets (GSE28829 and GSE17901) as well as clinical samples. In the end, single-sample gene set enrichment analysis (ssGSEA) was utilized to assess the immune cell patterns in both AS and AAA. Additionally, the correlation between key crosstalk genes and immune cell was evaluated. Results: In comparison to control group, both AS and AAA patients exhibited a decrease in fatty acid metabolism score. We found 40 DFRGs overlapping in AS and AAA, with lipid and amino acid metabolism critical in their pathogenesis. PCBD1, ACADL, MGLL, BCKDHB, and IDH3G were identified as signature genes connecting AS and AAA. Their expression levels were confirmed in validation datasets and clinical samples. The analysis of immune infiltration showed that neutrophils, NK CD56dim cells, and Tem cells are important in AS and AAA development. Correlation analysis suggested that these signature genes may be involved in immune cell infiltration. Conclusion: The fatty acid metabolism pathway appears to be linked to the development of both AS and AAA. Furthermore, PCBD1, ACADL, MGLL, BCKDHB, and IDH3G have the potential to serve as diagnostic markers for patients with AS complicated by AAA.
Our previous study showed that pyridoxine 5'-phosphate oxidase (PNPO) is a tissue biomarker of ovarian cancer (OC) and has a prognostic implication but detailed mechanisms remain unclear. The current study focused on PNPO-regulated lysosome/autophagy-mediated cellular processes and the potential role of PNPO in chemoresistance. We found that PNPO was overexpressed in OC cells and was a prognostic factor in OC patients. PNPO significantly promoted cell proliferation via the regulation of cyclin B1 and phosphorylated CDK1 and shortened the G2M phase in a cell cycle. Overexpressed PNPO enhanced the biogenesis and perinuclear distribution of lysosomes, promoting the degradation of autophagosomes and boosting the autophagic flux. Further, an autolysosome marker LAMP2 was upregulated in OC cells. Silencing LAMP2 suppressed cell growth and induced cell apoptosis. LAMP2-siRNA blocked PNPO action in OC cells, indicating that the function of PNPO on cellular processes was mediated by LAMP2. These data suggest the existence of the PNPO-LAMP2 axis. Moreover, silencing PNPO suppressed xenographic tumor formation. Chloroquine counteracted the promotion effect of PNPO on autophagic flux and inhibited OC cell survival, facilitating the inhibitory effect of PNPO-shRNA on tumor growth in vivo. Finally, PNPO was overexpressed in paclitaxel-resistant OC cells. PNPO-siRNA enhanced paclitaxel sensitivity in vitro and in vivo. In conclusion, PNPO has a regulatory effect on lysosomal biogenesis that in turn promotes autophagic flux, leading to OC cell proliferation, and tumor formation, and is a paclitaxel-resistant factor. These data imply a potential application by targeting PNPO to suppress tumor growth and reverse PTX resistance in OC.
OBJECTIVE: Cervical cancer (CC) is one of the most common gynecologic malignancies worldwide. Although rapid improvements have been made regarding its prevention and treatment, little is known about disease pathogenesis and the clinical relevance of reliable biomarkers. The present study evaluated the expression of cystatin B (CSTB) as a potential biomarker of CC. METHODS: Tissue microarray analysis and immunohistochemical staining were performed to detect CSTB expression, while CSTB mRNA and protein expression levels of freshly isolated CC tissue were measured by quantitative real-time PCR and western blot, respectively. Bioinformatics were used to analyze the CSTB co-expression network and functional enrichments. RESULTS: We observed high CSTB mRNA and protein expression levels in CC tissues, which was confirmed by tissue microarray in a comparison with paired adjacent non-cancerous cervical tissue samples. CSTB gene enrichments and associations with co-expressed genes were also observed. Further analysis showed that elevated CSTB expression was associated with pathological progress in CC. CONCLUSION: Our data demonstrate that CSTB has the potential to be used as a tissue biomarker with clinical value in patients with CC, which may aid the development of intervention strategies.
Cystatin B , Uterine Cervical Neoplasms , Female , Humans , Biomarkers , Blotting, Western , Cystatin B/genetics , RNA, Messenger , Uterine Cervical Neoplasms/genetics
Prostate cancer (PCa), especially castration-resistant PCa, is a common and fatal disease. Anillin (ANLN) is an actin-binding protein that is involved in various malignancies, including PCa. However, the regulatory mechanism of ANLN in PCa remains unclear. Exploring the role of ANLN in PCa development and discovering novel therapeutic targets are crucial for PCa therapy. In the current work, we discovered that ANLN expression was considerably elevated in PCa tissues and cell lines when compared to nearby noncancerous prostate tissues and normal prostate epithelial cells. ANLN was associated with more advanced T stage, N stage, higher Gleason score, and prostate-specific antigen (PSA) level. In addition, we discovered that overexpression of ANLN promoted PCa cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, we performed RNA-seq to identify the regulatory influence of ANLN on the MAPK signal pathway. Furthermore, a favorable association between ANLN expression and IGF2BP1 expression was identified. The tumor-suppressive impact of ANLN downregulation on PCa cell growth was partially reversed by overexpressing IGF2BP1. Meanwhile, we discovered that ANLN can stabilize the proto-oncogene c-Myc and activate the MAPK signaling pathway through IGF2BP1. These findings indicate that ANLN could be a potential therapeutic target in PCa.
Metastatic progression is the primary cause of mortality in prostate cancer (PCa) patients. Although circular RNAs (circRNAs) have been implicated in cancer progression and metastasis, our current understanding of their role in PCa metastasis remains limited. In this study, we identified that circUBE3A(2,3,4,5), which originated from exons 2, 3, 4 and 5 of the human ubiquitin-protein ligase E3A (UBE3A) gene, was specifically downregulated in PCa tissues and correlated with the Gleason score, bone metastasis, and D'Amico risk classification. Through the in vitro and in vivo experiments, we demonstrated that overexpression of circUBE3A(2,3,4,5) inhibited PCa cell migration, invasion, metastasis, and proliferation. Mechanistically, circUBE3A(2,3,4,5) was found to bind to adenylate-uridylate-rich binding factor 1 (AUF1), promoting the translocation of AUF1 into the nucleus. This led to decreased AUF1 in the cytoplasm, resulting in methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) mRNA instability and a subsequent reduction at the protein level. The downregulation of MTHFD2 further inhibited vimentin expression, thereby suppressing PCa cell epithelial-mesenchymal transition. Additionally, two pairs of the short-inverted repeats (TSIRs) in flanking introns were identified to synergistically facilitate the generation of circUBE3A(2,3,4,5) and other circRNAs. In summary, TSIRs-induced circUBE3A(2,3,4,5) acts as a suppressor of PCa metastasis by enhancing AUF1 nuclear translocation, reducing MTHFD2, and subsequently inhibiting vimentin expression. This study characterizes circUBE3A(2,3,4,5) as a functional circRNA and proposes it as a highly promising target for preventing PCa metastasis.
Prostatic Neoplasms , RNA, Circular , Humans , Male , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , Neoplasm Grading , Prostatic Neoplasms/pathology , RNA, Circular/genetics , Vimentin/metabolism
BACKGROUND: Ovarian cancer (OC) is the deadliest malignant tumor in women with a poor prognosis due to drug resistance and lack of prediction tools for therapeutic responses to anti- cancer drugs. OBJECTIVE: The objective of this study was to launch a prediction model for therapeutic responses in OC patients. METHODS: The RNA-seq technique was used to identify differentially expressed paclitaxel (PTX)- resistant lncRNAs (DE-lncRNAs). The Cancer Genome Atlas (TCGA)-OV and ImmPort database were used to obtain immune-related lncRNAs (ir-lncRNAs). Univariate, multivariate, and LASSO Cox regression analyses were performed to construct the prediction model. Kaplan- Meier plotter, Principal Component Analysis (PCA), nomogram, immune function analysis, and therapeutic response were applied with Genomics of Drug Sensitivity in Cancer (GDSC), CIBERSORT, and TCGA databases. The biological functions were evaluated in the CCLE database and OC cells. RESULTS: The RNA-seq defined 186 DE-lncRNAs between PTX-resistant A2780-PTX and PTXsensitive A2780 cells. Through the analysis of the TCGA-OV database, 225 ir-lncRNAs were identified. Analyzing 186 DE-lncRNAs and 225 ir-lncRNAs using univariate, multivariate, and LASSO Cox regression analyses, 9 PTX-resistant immune-related lncRNAs (DEir-lncRNAs) acted as biomarkers were discovered as potential biomarkers in the prediction model. Single-cell RNA sequencing (scRNA-seq) data of OC confirmed the relevance of DEir-lncRNAs in immune responsiveness. Patients with a low prediction score had a promising prognosis, whereas patients with a high prediction score were more prone to evade immunotherapy and chemotherapy and had poor prognosis. CONCLUSION: The novel prediction model with 9 DEir-lncRNAs is a valuable tool for predicting immunotherapeutic and chemotherapeutic responses and prognosis of patients with OC.
Background: Meteorological factors play an important role in human health. Clarifying the occurrence of dog and cat bites (DCBs) under different meteorological conditions can provide key insights into the prevention of DCBs. Therefore, the objective of the study was to explore the relationship between meteorological factors and DCBs and to provide caution to avoid the incidents that may occur by DCBs. Methods: In this study, data on meteorological factors and cases of DCBs were retrospectively collected at the Shanghai Climate Center and Jinshan Hospital of Fudan University, respectively, in 2016-2020. The distributed lag non-linear and time series model (DLNM) were used to examine the effect of meteorological elements on daily hospital visits due to DCBs. Results: A total of 26,857 DCBs were collected ranging from 1 to 39 cases per day. The relationship between ambient temperature and DCBs was J-shaped. DCBs were positively correlated with daily mean temperature (rs = 0.588, P < 0.01). The relative risk (RR) of DCBs was associated with high temperature (RR = 1.450; 95% CI [1.220-1.722]). Female was more susceptible to high temperature than male. High temperature increased the risk of DCBs. Conclusions: The extremely high temperature increased the risk of injuries caused by DCBs, particularly for females. These data may help to develop public health strategies for potentially avoiding the occurrence of DCBs.
Cat Diseases , Dog Diseases , Dogs , Female , Male , Animals , Humans , Cats , Emergency Room Visits , Retrospective Studies , China/epidemiology , Meteorological Concepts
Ovarian cancer (OC) is a fatal gynecologic disease. The most common treatment for OC patients is surgery combined with chemotherapy but most patients at advanced stages eventually develop relapse due to chemoresistance. This study examined the role and function of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in OC. We observed that the expression of IGF2BP2 mRNA and protein was up-regulated in OC cells and tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. An increase in IGF2BP2 expression at mRNA and protein levels was verified by the analyses of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), respectively. Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were applied to analyze the expression and clinical value of IGF2BP2. Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses explored biological functions and the involvement of IGF2BP2 in cell growth. Indeed, the knockdown of IGF2BP2 resulted in the inhibition of OC cell proliferation evaluated by the Cell Counting Kit-8 assay. Genomic amplification of IGF2BP2 partly accounted for its overexpression. High expression of IGF2BP2 was associated with signal transducer and activator of transcription 1 (STAT1) and drug sensitivity and was correlated with an unfavorable survival outcome in OC patients. Furthermore, the responsiveness of chemotherapy and immunotherapy were analyzed using the "pRRophetic" R package and The Cancer Immune Atlas (TCIA) database, respectively. The low expression of IGF2BP2 was associated with chemoresistance but with high tumor microenvironment scores and tumor-infiltrating immune cells, suggesting that immunotherapy may apply in chemoresistant patients. The alteration of IGF2BP2 expression may respond to chemotherapy and immunotherapy. Thus, IGF2BP2 shows potential as a therapeutic target and diagnostic biomarker for OC.
Insulin-Like Peptides , Ovarian Neoplasms , Humans , Female , Proteomics , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Immunotherapy , Biological Assay , Tumor Microenvironment , RNA-Binding Proteins/genetics
The rate constants kH (kD) have been determined at 27 °C for H· (D·) transfer from CpCr(CO)3H(D) to the C=C bonds of various enamides. This process leads to the formation of α-amino radicals. Vinyl enamides with N-alkyl and N-phenyl substituents have proven to be good H· acceptors, with rate constants close to those of styrene and methyl methacrylate. A methyl substituent on the incipient radical site decreases kH by a factor of 4; a methyl substituent on the carbon that will receive the H· decreases kH by a factor of 380. The measured kH values indicate that these α-amino radicals can be used for the cyclization of enamides to pyrrolidines. A vanadium hydride, HV(CO)4(dppe), has proven more effective at the cyclization of enamides than Cr or Co hydrides-presumably because the weakness of the V-H bond leads to faster H· transfer. The use of the vanadium hydride is operationally simple, employs mild reaction conditions, and has a broad substrate scope. Calculations have confirmed that H· transfer is the slowest step in these cyclization reactions.
PURPOSE: This study aimed to compare a dual Proglide strategy versus a combination of one Proglide and dual Exoseal for large-bore access closure during percutaneous access endovascular aneurysm repair (pEVAR). MATERIALS AND METHODS: We retrospectively analyzed 97 patients who underwent pEVAR at our center between January 2021 and February 2023. The patients were divided into two groups: dual Proglide (P + P) and one Proglide with dual Exoseal (P + E). The primary outcome measures were technical success and access-related vascular complications. Technical success was defined as achieving complete hemostasis without a bailout strategy. Postprocedural follow-up for access-related vascular complications was evaluated at 30 and 60 days using computed tomography angiography and ultrasonography. Severity was graded according to the Cardiovascular Interventional Radiological Society of Europe (CIRSE) Classification. RESULTS: Overall, a dual Proglide strategy was used in 46 patients (47.4%) with 65 groins (46.4%), and a combination of one Proglide and dual Exoseal was used in 51 patients (52.6%) with 75 groins (53.6%). The baseline characteristics were similar between the groups. The total technical success rate was 96.4%, and no significant differences were observed (95.4% vs. 97.3%; p = 0.870). Minor bleeding treatable through compression occurred significantly more often in the P group (CIRSE 1, 10.8% vs. 1.3%, p = 0.042). Hemostasis time, procedural time, length of stay in the hospital, closure device failure, and incidence of unplanned intervention did not differ significantly between the groups. CONCLUSIONS: A combined Proglide and Exoseal strategy is safe and effective for large-bore access closure during pEVAR and can be considered an alternative. However, it should be supported by larger prospective studies.
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Vascular Closure Devices , Humans , Aortic Aneurysm, Abdominal/surgery , Endovascular Aneurysm Repair , Prospective Studies , Retrospective Studies , Treatment Outcome , Hemostasis , Sutures , Femoral Artery/surgery , Hemostatic Techniques
Cyclin dependent kinase 14 (CDK14) plays a central role in the control of cell proliferation and cell cycle progression. However, the specific function and regulatory mechanism of CDK14 on paclitaxel (PTX) resistance in ovarian cancer (OC) remain unclear. The present study demonstrated that CDK14 was overexpressed in OC tissues and cells at mRNA and protein levels detected by qRT-PCR, Western blot, and immunohistochemistry. Survival analysis showed that elevated CDK14 was related to the poor prognosis of OC patients. Overexpression of CDK14 was correlated with chemoresistance in OC. The expression level of CDK14 was higher in PTX-resistant OC cells (SK3R-PTX and OV3R-PTX) than in their counterpart-sensitive cells (SK-OV-3 and OVCAR-3). Knockdown of CDK14 decreased multidrug resistance 1 (MDR1) and ß-catenin expression in SK3R-PTX and OV3R-PTX cells and resensitized OC cells to PTX by decreasing cell proliferation and inducing cell apoptosis. Administration of transforming growth factor (TGF)-ß1 decreased CDK14 protein in PTX-resistant OC cells. The inhibitory effect of TGF-ß1 on CDK14 expression was abolished in the presence of a TGF-ß type I receptor kinase inhibitor (SB-431542). Furthermore, TGF-ß signal transducer Smad2 protein directly bound to the region -437 to -446 upstream of the CDK14 transcription start site (TSS), resulting in downregulating the expression of CDK14. These data indicate that CDK14 is a PTX-resistant marker and is regulated by the TGF-ß signaling pathway. Targeting CDK14 to enhance the sensitivity of PTX may provide a new therapeutic strategy for reversing the PTX resistance in OC.
BACKGROUND/AIMS: The current study investigated the incidence, risk factors, and outcomes of acute pancreatitis after percutaneous transhepatic biliary stenting for malignant biliary obstruction. MATERIALS AND METHODS: From March 2016 to May 2020, a total of 425 patients who underwent percutaneous transhepatic biliary stent- ing for malignant biliary obstruction were included in this 2-center study. After the procedure, we analyzed the incidence, risk factors, and outcomes of acute pancreatitis. RESULTS: On follow-up, 79 (18.6%) patients showed increased serum amylase levels, of whom 41 (9.6%) developed pancreatitis. On binary logistic regression analysis, stent across the duodenal papilla (odds ratio = 8.54; 95% CI = 3.54-20.62; P < .001) and visualization of the pancreatic duct (odds ratio = 9.87; 95% CI = 4.67-20.86; P < .001) were significant risk factors of pancreatitis after the procedure. Using conservative therapy, all patients were successfully managed at a mean of 3.5 days (range 1-6 days), and no severe pancreatitis happened. CONCLUSION: Acute pancreatitis is a relatively common complication after percutaneous transhepatic biliary stenting. Stent across the duodenal papilla and visualization of the pancreatic duct are independent risk factors.
Cholestasis , Pancreatitis , Humans , Pancreatitis/etiology , Retrospective Studies , Acute Disease , Cholestasis/surgery , Cholestasis/complications , Stents/adverse effects , Treatment Outcome
Ovarian cancer (OC) lacks effective biomarkers for diagnosis at an early stage and often develops chemoresistance after the initial treatment at an advanced stage. RNAbinding motif protein 15 (RBM15) is an RNA m6A methylation mediator that serves an oncogenic role in some cancers. However, the function and molecular mechanisms of RBM15 in ovarian tumorigenesis and chemoresistance remain to be elucidated. The present study identified the overexpression of RBM15 in OC tissues and paclitaxel (PTX)resistant cells using reverse transcriptionquantitative (q)PCR, western blotting and immunohistochemistry. Clinical data analyses showed that high expression of RBM15 was associated with poor prognosis in patients with OC. Overexpression of RBM15 led to an increase in cell viability and colony formation and a decrease in cell sensitivity to PTX and apoptosis, whereas the knockdown of RBM15 resulted in the inhibition of cell viability and colony formation in vitro and tumor formation in vivo and increased cell apoptosis and sensitivity to PTX in a time and dosedependent manner. Furthermore, RBM15 knockdown reduced the spheroid formation of PTXresistant OC cells. Silencing of RBM15 decreased multidrug resistance 1 (MDR1) mRNA m6A methylation detected by the methylated RNA immunoprecipitationqPCR assay and downregulated the expression of a chemodrug efflux pump MDR1 at the mRNA and protein levels. Finally, RBM15 expression was suppressed by the activation of the TGFß signaling pathway. Thus, the findings revealed a TGFß/RBM15/MDR1 regulatory mechanism. Targeting RBM15 may provide a novel therapeutic strategy for the treatment of PTXresistant OC.
Ovarian Neoplasms , Paclitaxel , Humans , Female , Methylation , Paclitaxel/pharmacology , RNA, Messenger , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , RNA , Signal Transduction , RNA-Binding Proteins/genetics
BACKGROUND: Protocell refers to the basic unit of life and synthetic molecular assembly with cell structure and function. The protocells have great applications in the field of biomedical technology. Simulating the morphology and function of cells is the key to the preparation of protocells. However, some organic solvents used in the preparation process of protocells would damage the function of the bioactive substance. Perfluorocarbon, which has no toxic effect on bioactive substances, is an ideal solvent for protocell preparation. However, perfluorocarbon cannot be emulsified with water because of its inertia. METHODS: Spheroids can be formed in nature even without emulsification, since liquid can reshape the morphology of the solid phase through the scouring action, even if there is no stable interface between the two phases. Inspired by the formation of natural spheroids such as pebbles, we developed non-interfacial self-assembly (NISA) of microdroplets as a step toward synthetic protocells, in which the inert perfluorocarbon was utilized to reshape the hydrogel through the scouring action. RESULTS: The synthetic protocells were successfully obtained by using NISA-based protocell techniques, with the morphology very similar to native cells. Then we simulated the cell transcription process in the synthetic protocell and used the protocell as an mRNA carrier to transfect 293T cells. The results showed that protocells delivered mRNAs, and successfully expressed proteins in 293T cells. Further, we used the NISA method to fabricate an artificial cell by extracting and reassembling the membrane, proteins, and genomes of ovarian cancer cells. The results showed that the recombination of tumor cells was successfully achieved with similar morphology as tumor cells. In addition, the synthetic protocell prepared by the NISA method was used to reverse cancer chemoresistance by restoring cellular calcium homeostasis, which verified the application value of the synthetic protocell as a drug carrier. CONCLUSION: This synthetic protocell fabricated by the NISA method simulates the occurrence and development process of primitive life, which has great potential application value in mRNA vaccine, cancer immunotherapy, and drug delivery.
Background: It is well known that patients with systemic lupus erythematosus (SLE) had a high risk of venous thromboembolism (VTE). This study aimed to identify the crosstalk genes between SLE and VTE and explored their clinical value and molecular mechanism initially. Methods: We downloaded microarray datasets of SLE and VTE from the Gene Expression Omnibus (GEO) dataset. Differential expression analysis was applied to identify the crosstalk genes (CGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the shared genes. The shared diagnostic biomarkers of the two diseases were further screened from CGs using least absolute shrinkage and selection operator (Lasso) regression. Two risk scores for SLE and VTE were constructed separately to predict the likelihood of illness according to the diagnostic biomarkers using a logical regression algorithm. The immune infiltration levels of SEL and VTE were estimated via the CIBERSORT algorithm and the relationship of CGs with immune cell infiltration was investigated. Finally, we explored potential phenotype subgroups in SLE and VTE based on the expression level of CGs through the consensus clustering method and studied immune cell infiltration in different subtypes. Result: A total of 171 CGs were obtained by the intersection of differentially expressed genes (DEGs) between SLE and VTE cohorts. The functional enrichment shown these CGs were mainly related to immune pathways. After screening by lasso regression, we found that three hub CGs (RSAD2, HSP90AB1, and FPR2) were the optimal shared diagnostic biomarkers for SLE and VTE. Based on the expression level of RSAD2 and HSP90AB1, two risk prediction models for SLE and VTE were built by multifactor logistic regression and systemically validated in internal and external validation datasets. The immune infiltration results revealed that CGs were highly correlated with multiple infiltrated immunocytes. Consensus clustering was used to respectively regroup SLE and VTE patients into C1 and C2 clusters based on the CGs expression profile. The levels of immune cell infiltration and immune activation were higher in C1 than in C2 subtypes. Conclusion: In our study, we further screen out diagnostic biomarkers from crosstalk genes SLE and VTE and built two risk scores. Our findings reveal a close relationship between CGs and the immune microenvironment of diseases. This provides clues for further exploring the common mechanism and interaction between the two diseases.
Lupus Erythematosus, Systemic , Venous Thromboembolism , Humans , Venous Thromboembolism/genetics , Algorithms , Computational Biology , Lupus Erythematosus, Systemic/genetics , Biomarkers
Chemoresistance is the main cause of chemotherapy failure in ovarian cancer (OC). The enhanced scavenging of reactive oxygen species (ROS) by the thioredoxin system resulted in insufficient intracellular concentrations of effective ROS, leading to chemoresistance. To induce OC cell apoptosis by enhancing intracellular ROS levels, protoporphyrin IX (PpIX) and albumin-bound PTX nanoparticles (APNP) were utilized to fabricate APNP-PpIX nanoparticles. APNP-PpIX effectively generated ROS and increased the effective ROS concentration in chemoresistant cancer cells. The in vitro and in vivo experiments confirmed the effective inhibition of APNP-PpIX on chemoresistant OC cell proliferation and tumor formation. APNP-PpIX significantly improved the effectiveness of chemotherapy and photodynamic therapy, thus providing a new approach for the clinical treatment of chemoresistant OC.
Nanoparticles , Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/pharmacology , Reactive Oxygen Species , Drug Resistance, Neoplasm , Photochemotherapy/methods , Cell Line, Tumor
