INTRODUCTION:Exosomes, particularly those derived from mesenchymal stem cells, play an important role in treating and diagnosing various diseases. Hydrogels have been demonstrated to be suitable materials for encapsulating exosomes to preserve their biological activity and enable controlled release. Recently, the incorporation of exosomes into hydrogels has emerged as an important research field. This study aims to reveal trends and hotspots of exosome-hydrogel research results over the last 10 years. MATERIALS AND METHODS:Publications about exosome-hydrogel between 2013 and 2023 were searched from the Web of Science Core Collection. VOSviewer (version 1.6.18), CiteSpace (version 6.2.R2), the R package "bibliometric" (version 3.2.1), and Scimago Graphica were employed for further bibliometric analysis and data visualization. RESULTS:From January 2013 to December 2023, 1354 documents (1093 articles and 261 reviews) were written by 7651 authors from 1612 institutions across 72 countries and published in 392 journals. China had the highest number of publications (630), and Shanghai Jiaotong University published the most articles (53). Soft Matter is the most prolific journal (36 documents, average citation: 19.8%), whereas ACS Nano (25 documents, average citation: 70.3%) is the most authoritative journal in this field. Z Gu (13 documents) and A Hao (10 documents) were the most productive authors. The most popular keywords were "hydrogel," "vesicles," "exosomes," "drug delivery," "nanoparticles," "release," and "mesenchymal stem cells." Furthermore, our findings indicated that exosome-hydrogel compounds were most frequently used in diabetic wound healing and bone regeneration. CONCLUSIONS:This study revealed a growing interest in exosome-hydrogel for managing related diseases, especially, diabetic wound healing and bone regeneration. This study offers new insights into research fields of exosome-hydrogel, and may benefit further research.

Gastric cancer is a common and highly invasive type of malignant tumor, the pathogenesis of which remains unclarified. However, exosomes are now known to play important roles in gastric cancer development and treatment. Cells use exosomes for the packaging and transportation of a variety of bioactive molecules, such as proteins, double-stranded DNA, and micro-ribonucleic acids, to other sites. Exosome-specific membrane structures and exosomal contents are widely involved in processes that facilitate material exchange and intercellular communication between gastric cancer cells. They help in forming a pre-metastatic microenvironment, promoting the proliferation and apoptosis of gastric cancer cells, and driving invasion, metastasis, and resistance to anti-tumor drugs. In this review, we aimed to summarize the findings of research articles indexed in the PubMed, Web of Science, and Embase databases and published up to May 31, 2024, on the role of exosomes in the pathogenesis of gastric cancer and their potential clinical applications in its treatment. Thus, research on exosomes may lead to breakthroughs in the early diagnosis of gastric cancer and identification of novel treatments.

Endometrial cancer (EC) is a common malignant tumor in the female reproductive system. Circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification are widely involved in cancer progression. Nevertheless, the cross-talk between circ-NAB1 and m6A as well as the biological functions of circ-NAB1 in EC remain unclear. Circ-NAB1 was observed to be upregulated in EC tissues and cells by RT-qPCR. MeRIP and RNA pull-down assays were utilized for detecting the m6A modification of circ-NAB1. The interaction between circ-NAB1 and RNAs was also detected. Colony formation, transwell, flow cytometry, and western blot were utilized for measuring EC cell behaviors. Mechanically, we proved the m6A demethylase alkylation repair homolog protein 5 (ALKBH5) can mediate circ-NAB1 expression through an m6A-YTHDF2-dependent manner. Circ-NAB1 overexpression can promote cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) process, and cell cycle through functional assays. Circ-NAB1 knockdown exerts the opposite function on EC cells. Furthermore, we proved that circ-NAB1 can sponge miR-876-3p to upregulate the target gene cyclin-dependent kinase inhibitor 3 (CDKN3) in EC cells. CDKN3 overexpression can reverse the impacts of circ-NAB1 depletion on EC cell behaviors. Collectively, we proved that ALKBH5-mediated m6A modification of circ-NAB1 promoted EMT process and cell cycle in EC via targeting the miR-876-3p/CDKN3 axis.

Despite advances in understanding breast cancer (BC) molecular subtypes, the mechanisms underlying its grade of malignancy remain unclear. Our study reveals that low expression of the RNA-binding protein ELAVL1 is linked to higher-grade malignancy and poorer prognosis in malignant BC subtypes. Notably, knockdown of ELAVL1 increased the expression of key stem cell markers (CD44, SOX2, OCT4, KLF4, and NANOG) and enhanced tumorsphere formation. These findings offer new insights into BC malignancy and suggest potential improvements in prognostic assessment and treatment strategies for better patient outcomes.

Interleukin (IL)-36 is a member of the IL-1 superfamily, which includes three receptor agonists and one antagonist and exhibits a familial feature of inflammatory regulation. Distributed among various tissues, such as the skin, lung, gut and joints, the mechanism of IL-36 has been most completely investigated in the skin and has been used in clinical treatment of generalized pustular psoriasis. Meanwhile, the role of IL-36 in the intestine has also been under scrutiny and has been shown to be involved in the regulation of various intestinal diseases. Inflammatory bowel disease and colorectal cancer are the most predominant inflammatory and neoplastic diseases of the intestine, and multiple studies have identified a complex role for IL-36 in both of them. Indeed, inhibiting IL-36 signaling is currently regarded as a promising therapeutic approach. Therefore, the present review briefly describes the composition and expression of IL-36 and focuses on the role of IL-36 in intestinal inflammation and colorectal cancer. The targeted therapies that are currently being developed for the IL-36 receptor are also discussed.

Object. β-Elemene is an emerging antitumor Chinese medicine, but the exact mechanism of action of β-elemene in colorectal cancer (CRC) remains unclear. This study aimed to explore the mechanism of the lncRNA-miRNA-mRNA network in the process of β-elemene inhibiting CRC. Methods. RNA sequencing was performed on CRC cells from the control group (untreated) and the case group (β-elemene-treated). According to the sequencing data, we screened the differentially expressed (DE) lncRNAs, miRNAs, and mRNAs and then analyzed them by functional enrichment analyses. Through the lncRNA-miRNA-mRNA network, the key miRNAs and mRNAs involved in the process of β-elemene inhibiting CRC were further identified. Results. Totally, 607 upregulated and 599 downregulated DElncRNAs, 12 downregulated and 24 upregulated DEmiRNAs, and 3153 downregulated and 3248 upregulated DEmRNAs were identified. Through the lncRNA-miRNA-mRNA network, 3 miRNAs (miR-7109-3p, miR-4506, and miR-3182), 7 prognostic mRNAs (ALPG, DTX1, HOXD13, RIMS3, SLC16A8, SYT1, and TNNT1), and 2 key mRNAs (RIMS3 and SLC16A8) were determined to participate in the inhibitory mechanism of β-elemene in CRC. Conclusion. This study revealed for the first time that the lncRNA-miRNA-mRNA network is involved in the regulation of β-elemene in CRC, and these identified miRNAs and mRNAs could be new clinical prognostic biomarkers and therapeutic targets for CRC patients.

Objective:The purpose of this study is to screen for microRNAs (miRNAs) associated with the prognosis of lung adenocarcinoma (LUAD) and to explore its prognosis and effects on the tumor microenvironment in patients with LUAD.Methods:Gene expression data, miRNA expression data, and clinical data for two different databases, TCGA-LUAD and CPTAC-3 LUAD, were downloaded from the GDC database. The miRNA prognosis of LUAD was filtered by the Cox proportional hazard model and the Least Absolute Shrinkage and Selection Operator (LASSO) regression model. The performance of the model was validated by time-dependent receiver operating characteristics (ROC) curves. Possible biological processes associated with the miRNAs target gene were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the prognostic model was scored by risk, divided into high- and low-risk groups by median, and the differences in the immersion level of 21 immune cells in the high- and low-risk groups were assessed. To gain a deeper understanding of the underlying mechanism behind the model, the two most important miRNAs in the model, miR-195-3p and miR-5571-5p, were selected for HPA database validation and ceRNA network construction.Results:Of the 209 variance expressions identified in the screening analysis, 145 were upregulated and 64 were downregulated by miRNAs. The prognostic models of six miRNA genes were obtained: miR-195-3p, miR-5571-5p, miR-584-3p, miR-494-3p, miR-4664-3p, and miR-1293. These six genes were significantly associated with survival rates in LUAD patients. In particular, miR-1293, miR-195-3p, and miR-5571-5p are highly correlated with OS. The higher expression of miR-195-3p and miR-5571-5p, the better survival of LUAD OS is, and these two miRNA expressions contribute the most to the model. Finally, after sorting the risk scores calculated from low to high using the prognostic model, the patients with higher scores had shorter survival time and higher frequency of death, and there were significant differences in the immersion levels of 21 immune cells in the high- and low-risk groups. ceRNA network analysis found that TM9SF3 was regulated by miR-195-3p and was highly expressed in the tissues of LUAD patients, and the prognosis of the patients was poor.Conclusions:miR-195-3p, miR-5571-5p, miR-584-3p, miR-494-3p, miR-4664-3p, and miR-1293 may be used as new biomarkers for prognosis prediction of LUAD. Our results also identified a lncRNA MEG3/miR-195-3p/RAB1A/TM9SF3 regulatory axis, which may also play an important role in the progression of LUAD. Further study needs to be conducted to verify this result.

RNAmodifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N-6-methyladenosine (m(6)A) on messengerRNA(mRNA) plays critical roles in cell fate determination and development. m(6)A mark also resides in the decoding center of 18S ribosomalRNA(rRNA); however, the biological function of m(6)A on 18SrRNAis still poorly understood. Here, we report that methyltransferase-like 5 (METTL5) methylates 18SrRNAbothin vivoandin vitro, which is consistent with previous reports. Deletion ofMettl5causes a dramatic differentiation defect in mouse embryonic stem cells (mESCs). Mechanistically, the m(6)A deposited byMETTL5 is involved in regulating the efficient translation of F-box andWDrepeat domain-containing 7 (FBXW7), a key regulator of cell differentiation. Deficiency ofMETTL5 reducesFBXW7 levels and leads to the accumulation of its substrate c-MYC, thereby delaying the onset ofmESCdifferentiation. Our study uncovers an important role ofMETTL5-mediated 18S m(6)A inmESCdifferentiation through translation regulation and provides new insight into the functional significance ofrRNAm(6)A.

Long non‐coding RNAs have been demonstrated to be important regulators of various cancers, though the precise mechanisms remain unclear. Although lincFOXF1 has been reported to act as a tumour suppressor, its function and underlying mechanisms in osteosarcoma have not yet been explored. We employed quantitative real‐time polymerase chain reaction (qRT‐PCR) to evaluate the expression of lincFOXF1 and GAPDH in osteosarcoma tissues and cell lines, and colony‐formation, CCK8, wound‐healing, and transwell assays were conducted to analyse the proliferation, migration, and invasion capacity of osteosarcoma cells. Subcellular localization analysis by fractionation and RNA immunoprecipitation assays were performed to elucidate the mechanism responsible for lincFOXF1‐mediated phenotypes of osteosarcoma cells. The results revealed that lincFOXF1 expression is significantly decreased and strongly related to Enneking stage as well as metastasis in osteosarcoma patients. Further experiments showed that lincFOXF1 inhibits the migration, invasion and metastasis of cells in vitro and vivo. Mechanistic investigation demonstrated that lincFOXF1 physically binds to EZH2, a polycomb repressive complex 2 (PRC2) component, and a search for downstream targets suggested that G‐protein‐coupled receptor kinase‐interacting protein 1 (GIT1) is involved in the lincFOXF1‐mediated repression of osteosarcoma cells migration and invasion. Moreover, GIT1 expression is inversely correlated with lincFOXF1 in osteosarcoma. The present findings indicate that lincFOXF1 is involved in the progression of osteosarcoma through binding with EZH2, further regulating GIT1 expression. Our results suggest that lincFOXF1 may serve as a biomarker and therapeutic target for osteosarcoma patients.

Protein Kinase D (PKD) family contains PKD1, PKD2, and PKD3 in human. Compared to consistent tumor-suppressive functions of PKD1 in breast cancer, how PKD2/3 functions in breast cancer are not fully understood. In the current study, we found that PKD2 and PKD3 but not PKD1 were preferentially overexpressed in breast cancer and involved in regulating cell proliferation and metastasis. Integrated phosphoproteome, transcriptome, and interactome showed that PKD2 was associated with multiple cancer-related pathways, including adherent junction, regulation of actin cytoskeleton, and cell cycle-related pathways. ELAVL1 was identified as a common hub-node in networks of PKD2/3-regulated phosphoproteins and genes. Silencing ELAVL1 inhibited breast cancer growth in vitro and in vivo. Direct interaction between ELAVL1 and PKD2 or PKD3 was demonstrated. Suppression of PKD2 led to ELAVL1 translocation from the cytoplasm to the nucleus without significant affecting ELAVL1 expression. Taken together, we characterized the oncogenic functions of PKD2/3 in breast cancer and their association with cancer-related pathways, which shed lights on the oncogenic roles and mechanisms of PKDs in breast cancer.

mTOR is a valuable oncotarget for osteosarcoma. The anti-osteosarcoma activity by a novel mTOR kinase inhibitor, CZ415, was evaluated. We demonstrated that CZ415 potently inhibited survival and proliferation of known osteosarcoma cell lines (U2OS, MG-63 and SaOs2), and primary human osteosarcoma cells. Further, CZ415 provoked apoptosis and disrupted cell cycle progression in osteosarcoma cells. CZ415 treatment in osteosarcoma cells concurrently blocked mTORC1 and mTORC2 activation. Intriguingly, ERK-MAPK activation could be a major resistance factor of CZ415. ERK inhibition (by MEK162/U0126) or knockdown (by targeted ERK1/2 shRNAs) dramatically sensitized CZ415-induced osteosarcoma cell apoptosis. In vivo, CZ415 oral administration efficiently inhibited U2OS tumor growth in mice. Its activity was further potentiated with co-administration of MEK162. Collectively, we demonstrate that ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo. CZ415 could be further tested as a promising anti-osteosarcoma agent, alone or in combination of ERK inhibition.

Acute postoperative pain following radical mastectomy is a high risk for prolonged convalescence and potential persistent pain in patients with breast cancer. The present study was designed to observe the effect of intraoperative use of dexmedetomidine on acute postoperative pain following radical mastectomy under general anesthesia. Forty-five patients were enrolled into the study and divided into two groups that were maintained with propofol/remifentanil/Ringer's solution or propofol/remifentanil/Dexmedetomidine followed by morphine-based patient-controlled analgesia. During the first 24 h following surgery, patients receiving dexmedetomine had lower NRS pain scores, decreased morphine consumption, longer time to first morphine request as well as a trending decreased incidence of adverse effects when compared to those received Ringer's solution. In conclusion, the present study finds that intraoperative use of dexmedetomidine could promote analgesic property of postoperative morphine.

Intraoperative dexemdetomidine (DEX) with or without loading dose is well-established to improve postoperative pain control in patient-controlled analgesia (PCA). This study was designed to compare the pro-analgesia effect between the 2 in patients received general anesthesia.Seventy patients shceduced abdominal surgery under general anesthesia were randomly assigned into 3 groups which were maintained using propofol/remifentanil/Ringer solution (PRR), propofol/remifentanil/dexmedetomidine with (PRDw) or without (PRDo) a loading dose of dexmedetomidine before induction.PRDw/o patients displayed a greater Romsay sedation score measured immediately after surgery. When compared with PRR patients, those from the PRDw/o group had an increased time to first request of postoperative morphine and decreased 24hours total morphine consumption. No significant difference was observed between patients from the PRDw and PRDo groups with respect to these parameters.The present study suggests that the administration of a DEX loading dose does not affect the pro-analgesic effect of intraoperative use of DEX on morphine-based PCA.

Excessive adipocyte differentiation and proliferation are closely associated with the onset of obesity, which has been partially linked to microRNA expression. In previous studies, using miRNA microarray screening, we found that miR-1275 was significantly decreased in human mature adipocytes. In this study, we examined the role of miR-1275 in adipogenesis. Our results indicated that miR-1275 can inhibit the differentiation of human visceral preadipocytes without affecting their proliferation. ELK1, an E-twenty-six (ETS)-domain transcription factor associated with adipocyte differentiation, was strongly suppressed by miR-1275 in human visceral adipocytes. This was demonstrated via a dual-luciferase reporter assay and pointed to ELK1 as a direct target of miR-1275. Furthermore, miR-1275 expression was significantly diminished in the visceral adipose tissue of overweight and obese human subjects accompanied by a negative correlation with body mass index. These results suggest that miR-1275 could play a future role in the management of obesity, as a novel therapeutic target or biomarker.

Chemotherapy has been extensively used in tumor treatment, including either systemic or local treatment. Miserably, in many kinds of cancers, chemotherapy is gradually insensitive. The mechanisms of tumor drug resistance have been widely explored, yet have not been fully characterized. With several studies in the development of drug resistance, recent works have highlighted the involvement of non-coding RNAs in tumor development. A growing number of long non-coding RNAs (lncRNAs) have been identified as transcripts of larger than 200 nucleotides in length, which have low coding potential, but potentially coding small peptides with 50–70 amino acids. Despite so often being branded as transcriptional noise, it is becoming increasingly clear that a large number of lncRNAs are crucial molecular regulators of the processes of tumor involving the initiation and progression of human tumor. More recently, accumulating evidence is revealing an important role of lncRNA in tumor drug resistance and lncRNA expression profiling can be correlated with the evolution of tumor drug resistance. The long non-coding-RNA-mediated form of drug resistance brings yet another mechanism of drug resistance. So, exploiting the newly emerging knowledge of lncRNAs for the development of new therapeutic applications to overcome human tumor drug resistance will be significant.

The transmembrane glycoprotein embigin (EMB) belongs to the immunoglobulin superfamily (IgSF) and a number of IgSF members have been identified as biomarkers for cancer progression. In this study, we show that embigin is transcriptionally regulated by Homeobox C8 (HOXC8) in breast cancer cells and embigin expression suppresses breast tumorigenesis. With aid of Western blot, luciferase reporter gene assay and chromatin immunoprecipitation, we reveal that HOXC8 binds to the EMB promoter at the region of nucleotides -2303 to -2315 and acts as a transcription inhibitor to suppress embigin expression. Depletion of embigin leads to increase in proliferation, anchorage-independent growth and migration of breast cancer cells, and the inhibitory effects mediated by HOXC8 knockdown on breast tumorigenesis can be largely rescued by depletion of embigin expression in breast cancer cells, suggesting that HOXC8 regulates breast tumorigenesis, at least partly, through regulating embigin expression. Moreover, we show that loss of embigin promotes proliferation, anchorage-independent growth, and migration ability of normal mammary epithelial MCF10A cells. The analyses of publically available human breast tumor microarray gene expression database show that low embigin levels correlate with short survival of breast tumor patients, particularly with basal-like tumor patients, and embigin expression is low specifically in patients with basal-like, ER-/HER2-tumors. Taken together, our study demonstrates that low/loss of embigin plays an important role in the progression of breast tumors.

BACKGROUNDTo investigated the diagnostic and prognostic value of engulfment and cell motility (ELMO3) in non small cell lung cancer (NSCLC).METHODSThe expression of ELMO3 at mRNA levels were detected using reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) in 125 NSCLC patients' tissues and adjacent tissues, as well as in the serum of 125 NSCLC patients and 89 healthy controls. Then, receiver operating characteristic curve (ROC), Kaplan-Meier and Cox regression analysis were adopted to estimate the potential diagnostic and prognostic value of ELMO3, respectively.RESULTSELMO3 expression level was significantly up-regulated in NSCLC patients' tissues and serum compared with controls (P<0.001). Moreover, the expression of ELMO3 was significantly associated with tumor size (P=0.020), TNM stage (P=0.017), lymph node metastasis (PP=0.045) and distance metastasis (P=0.033). ROC showed the AUC was 0.917, and the optimal cutoff value was 0.735, providing a sensitivity of 92.8% and a specificity of 84.3%. Furthermore, Kaplan-Meier analysis indicated the high expression of ELMO3 could lead to a shorter overall survival time. In multivariate analysis, ELMO3 expression (HR=3.378, 95% CI=1.326-8.587, P=0.011) was proved to be linked with the prognosis of NSCLC and might act as an independent prognostic marker.CONCLUSIONThe over-expression of ELMO3 was a potential diagnostic and prognostic marker for NSCLC.

BACKGROUND:This study was guided by principles of the theoretical system of evidence-based medicine. In particular, when searching for evidence of breast cancer, a measuring scale is an instrument for evaluating curative effects in accordance with the laws and characteristics of medicine and exploring the establishment of a system for medically assessing curative effects. At present, there exist few tools for evaluating curative effects. Patient- reported outcomes (PROs) refer to outcomes directly reported by patients (without input or explanations from doctors or other intermediaries) with respect to all aspects of their health. Data obtained from PROs provide evidence of treatment effects.MATERIALS AND METHODS:In accordance with the tenets of theoretical medicine and ancient medical theory regarding breast cancer, principles for developing a PRO scale were established, and a theoretical model was developed and a literature review was performed, items from this pool were combined and split, and an initial scale was constructed. After a pilot survey and additional modifications, a pre-questionnaire scale was formed and used in a field investigation. After the application of statistical methods, the item pool was used to create a formal scale. The reliability, validity and feasibility of this formal scale were then assessed.RESULTS:In a clinical investigation, 479 responses were recovered, with an acceptance rate of 95%. a combination of various methods was employed, and the items that were selected by all methods or more than half of the methods were employed in the questionnaire. In these cases, the screening methods were combined with certain features of the item, A total of four domains and 38 items were reserved. The reliability analysis indicated that the PRO scale was relatively reliable.CONCLUSIONS:Scientific assessment proved that the proposed scale exhibited good reliability and validity. This scale was readily accepted and could be used to assess the curative effects of medical therapy. However, given the limited scope of this investigation, the capacity for adapting this scale to incorporate other theories could not be determined.

Objectives: MiRNA-139 is located at 11q13.4 and it has anti-oncogenic and antimetastatic activity in humans. However, its role in controlling apoptosis, invasion and metastasis and the development of chemosensitivity to docetaxel in breast cancer cells are not fully understood. The aim of this study was to research the biological function of miR-139-5p and the efficacy of chemosensitivity to docetaxel.Methods: MiR-139-5p expression in MCF-7, MCF-7/Doc cells and in selected breast cancer tissue samples was confirmed by real-time PCR; cell viability was analyzed by Cell Counting Kit-8 assay; apoptosis and cell cycle were analyzed by flow cytometry; control of metastasis and invasion of breast cancer cells was measured by transwell assay; expression of Notch1 was measured by western blot; a luciferase reporter vector was constructed to identify the miR-139-5p target gene.Results: MiR-139-5p was significantly down-regulated in breast cancer cells. MiR-139-5p inhibits the viability of breast cancer cells. MiR-139-5p induces apoptosis, causes cell cycle arrest in S phase, inhibits migration and invasion in breast cancer cells, however, MiR-139-5p play the opposite role in docetaxel-induced breast cancer cells.Conclusions: MiR-139-5p not only attenuated the development of breast cancer cells but also mediated drug-resistance by regulating the expression of the downstream target gene Notch1. (C) 2015 Elsevier Inc. All rights reserved.

Acquired drug resistance is a major obstacle to chemotherapy of cancers. In this study, we aim to investigate the role of exosomes in drug-resistance transfer between breast cancer cells and detect the probable mechanism. A docetaxel-resistant variant of MCF-7 cell line (MCF-7/DOC) was established and then compared with the drug-sensitive variant (MCF-7/S). Exosomes were expelled from the cell supernatant using ultracentrifugation. Drug resistance was assessed by apoptosis assay and MTT examination. Expressions of P-glycoprotein (P-gp) were analyzed by flow cytometry. Stained exosomes were absorbed by receipt cells. MCF-7/S in the presence of exosomes extracted from the supernatant of MCF-7/DOC (DOC/exo) acquired drug resistance, while MCF-7/S exposed to their own exosomes (S/exo) did not. P-gp expression patterns of exosomes were similar as the originated cells. P-gp expression of MCF-7/S increased after incubation with DOC/exo and was affected by the amount of exosomes. Exosomes are effective in transferring drug resistance as well as P-gp from drug-resistant breast cancer cells to sensitive ones. The delivery of P-gp via exosomes may be a mechanism of exosome-mediated drug resistance transfer.