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1.
Clin Cancer Res ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947693

RESUMO

PURPOSE: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful non-invasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. EXPERIMENTAL DESIGN: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. 481 HCC and 517 liver cirrhosis (LC) patients were recruited in the study. RESULTS: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was firstly generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR>1) was identified as a potential HCC-related mutational hot-zone. CONCLUSIONS: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of non-invasive detection of virus insertion/mutation.

2.
Orthop Surg ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33942967

RESUMO

The aim of this systematic review was to characterize the clinical features of adults with Salmonella osteomyelitis and summarize diagnosis and treatment methods to provide guidance for clinicians. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a literature search in the PubMed, EMBASE, and Cochrane Library databases. Article screening and data extraction were performed by two reviewers individually. All the included studies were independently evaluated by two reviewers using the Methodological Index for Non-Randomized Studies (MINORS) criteria. A total of 67 articles published between 1970 and 2019 were selected, which include 69 patients with an average age of 47.5 years (range, 18-79).The majority of cases (47.76%) occurred in immunocompetent adults without common risk factors. Aspiration and biopsy cultures were all positive in Salmonella osteomyelitis patients who underwent aspiration or biopsy. All infections were monomicrobial, and a total of 12 different serotypes were identified. The three most commonly reported Salmonella serotypes were Salmonella typhi (19 cases), Salmonella typhimurium (12 cases), and Salmonella enteritidis (11 cases). Only 12 of the 67 cases in our data (17.91%) had diarrhea symptoms, and 44 of the 67 cases (65.67%) had fever symptoms. Fifty-nine of the 67 cases (88.06%) had local inflammatory manifestations, such as erythema, swelling, and tenderness in the affected area. The commonly reported involved sites were the vertebrae, femur, and tibia. Antibiotic therapy alone was utilized in 30 cases, and 24 patients (80.00%) were eventually cured. In total, 75.68% of patients achieved satisfactory results after treatment with surgery and antibiotics. Third-generation cephalosporins were most commonly utilized, and antibiotic treatment was administered for an average of 11.3 weeks (95% CI, 8.31-14.37 weeks). Salmonella osteomyelitis should be considered in patients without any common risk factors. Aspiration or biopsy can facilitate the identification of pathogens to guide antibiotic choice. Empirical therapy with a third-generation cephalosporin is recommended until the susceptibility of the strain is determined.

5.
Heart Vessels ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33512599

RESUMO

Ripple mapping can make the visualization of activation conduction on a 3-dimensional voltage map and is useful tool for scar-related organized atrial tachycardia (AT). This study sought to assess the efficacy of ripple mapping for interpreting reentrant circuits and critical isthmus in postoperative ATs. 34 consecutive patients with a history of mitral valve surgery (mean age, 54.5 ± 12.4 years) underwent high density (HD) RM during ATs with CARTO3v4 CONFIDENSE system. The voltage activation threshold was determined by RM over a bipolar voltage map. The identification of underlying mechanisms and ablation setting was based on RM without reviewing activation mapping. A total of 41 ATs (35 spontaneous, 6 induced) were characterized. 39 reentry circuits were successfully mapped (cycle length, 256 ± 43 ms). Of the 41 ATs, 28 were confirmed by ripple mapping alone (68%), and 12 (29%) by ripple mapping and entrainment mapping. Of 12 ATs in the left atrium, 9 (75%) needed entrainment to confirm, compared with 5 (17.8%) in the right atrium. Primary endpoint after initial ablation set was achieved in 32 of the 34 patients (94.1%). Freedom from atrial arrhythmias was 79.4% after the follow-up of 12 ± 5 months. Of the seven patients with recurrence, three underwent the repeated catheter ablation. Ripple mapping precisely delineated reentrant circuits in post-cardiac surgery AT resulting in a high success rate of ablation. Entrainment maneuvers remain useful for elucidation of complex AT circuits.

6.
Angew Chem Int Ed Engl ; 60(12): 6639-6645, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33314510

RESUMO

Self-resistance genes are employed by many microbial producers of bioactive natural products to avoid self-harm. Herein, we describe a unique strategy for self-resistance toward a macrolide antibiotic, A26771B (1), identified by elucidating its biosynthetic pathway in the fungus Penicillium egyptiacum. A highly reducing polyketide synthase and a trans-acting thioesterase generate the macrolide backbone, and a cytochrome P450 and an acyltransferase, respectively catalyze hydroxylation and succinylation to form the prodrug berkeleylactone E (2). Then, extracellular oxidative activation by a secreted flavin-dependent oxidase forms 1, while intracellular reductive inactivation by a short-chain reductase reforms 2, forming a redox cycle. Our work illustrates a unique redox-mediated resistance mechanism for fungal antibiotics and contributes to the understanding of antibiotic biosynthesis and resistance.

7.
Zhonghua Nan Ke Xue ; 26(8): 695-699, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-33377729

RESUMO

Objective: To investigate the expressions of Th1/Th2 cytokines and autoantibodies in the serum of the patients with idiopathic oligoasthenozoospermia (IO) and their significance. METHODS: From November 2017 to April 2020, we examined the levels of Th1/Th2 cytokines (IL-2, IL-4, IL-10, IL-21, TNF-α, IFN-γ) and the expressions of AhCGAb, AsAb and AcAb in the serum of 48 infertile men with mild or moderate IO, 48 with severe IO and another 72 males with normal semen parameters by ELISA. We compared the results of detection among the three groups and analyzed them with the logistic regression model. RESULTS: Compared with the normal controls, the patients with mild or moderate IO showed significant increases in the levels of IL-10, IL-21 and IFN-γ and the expressions of AhCGAb, AsAb and AcAb (P < 0.05), and so were those of the severe IO group in the levels of all the six cytokines and the expressions of the three autoantibodies (P < 0.05). The levels of IL-2, IL-4, IL-21 and TNF-α and the expressions of AhCGAb and AsAb were even higher in the patients with severe IO than in those with mild or moderate IO (P < 0.05). Multivariate logistic regression analysis showed that the increased levels of IL-21/IL-10 (OR = 1.694, 95% CI: 0.319-4.035, P < 0.05) and positive expressions of AhCGAb (OR = 4.357, 95% CI: 1.204-9.426, P < 0.05) and AsAb (OR = 2.135, 95% CI: 1.902-5.429, P < 0.05) were the risk factors for IO. CONCLUSIONS: The levels of the cytokines IL-2, IL-4, IL-10, IL-21, TNF-α and IFN-γ and the expressions of the autoantibodies AhCGAb, AsAb and AoAb are significantly higher in IO patients than in normal healthy males. Quantitative analysis of cytokines and autoantibodies in the serum of IO patients may provide some valuable information for studies of the pathogenesis of male infertility.


Assuntos
Astenozoospermia/sangue , Autoanticorpos/sangue , Citocinas/sangue , Estudos de Casos e Controles , Humanos , Masculino , Células Th1 , Células Th2
8.
Int J Clin Exp Pathol ; 13(10): 2628-2636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33165408

RESUMO

BACKGROUND: EPDR1 is widely expressed in cancer, especially colorectal cancer. However, the biologic function of EPDR1 in breast cancer is uncertain. METHODS: The expression profile of EPDR1 was assessed by Gene Expression Profiling Interactive Analysis (GEPIA; gepia.cancer-pku.cn). We constructed EPDR1-overexpressing (EPDR1-Ov) plasmids that were transfected into breast cancer cells (MCF-7 and MDA-MB-453) to examine the EPDR1 effect on their malignant behavior. The EPDR1 overexpression and the critical components of the P53 signaling pathway were determined by western blot or RT-PCR. Cell proliferation, colony formation, invasive capacity, and cell apoptotic proportions were examined after transfection. RESULTS: mRNA expression of EPDR1 was significantly lessened in breast cancer tissues when compared to the adjacent normal tissues by data analysis from GEPIA. There was an impairment in proliferative ability, viability, invasion, and anti-apoptotic effect in EPDR1 overexpressed breast cancer cells. Mechanistic studies showed that EPDR1 overexpression increased the p53, p21 and Bcl-2 expression while inhibiting Bax expression. CONCLUSION: EPDR1 inhibited malignant behaviors and promoted apoptosis in breast cancer cells by activation of the p53 signaling pathway.

10.
Opt Lett ; 45(19): 5456-5459, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001918

RESUMO

The aliasing effect in the discrete Fourier transform inherent will impose a serious detrimental effect on conventional phase retrieval measurement accuracy with under-sampled intensity. In this Letter, we describe a modal-based nonlinear optimization phase retrieval approach that is capable of retrieving wavefront measurements using under-sampled intensities. The extended Nijboer-Zernike theory is introduced to establish an analytic solution between wavefront phase and intensity image, and then nonlinear optimization is further utilized to solve wavefront aberration coefficients from under-sampled intensity data. The feasibility and accuracy of the algorithm are verified by simulations and experiments. This is a promising method that is especially suitable for full field phase recovery of optical systems with a relatively high numerical aperture.

11.
J Nat Prod ; 83(11): 3262-3269, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33064488

RESUMO

Seven new ß-caryophyllene derivatives, pestalotiphains A-G (1-7), along with six known analogues (8-13), were isolated from the plant-associated Pestalotiopsis hainanensis. Compound 1 represents the first example of a caryophyllene-adenine hybrid, and 2 contains a novel oxatricyclo[4.3.1.0] system. Their structures and absolute configurations were assigned by interpretation of a combination of spectroscopic data and electronic circular dichroism calculations. Compound 8 exhibited moderate inhibition of HL-60 and THP-1 cell lines (IC50, 6.2 and 2.0 µM, respectively). A candidate biosynthetic gene cluster responsible for these compounds was uncovered by bioinformatics analyses and confirmed by a biochemical approach.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33118183

RESUMO

BACKGROUND: Left bundle branch area pacing (LBBAP) is an innovative pacing technology, which needs further study. METHODS: 70 LBBAP patients with intrinsic QRS duration (QRSd) less than 120 ms were consecutively enrolled in our center. According to whether the left bundle branch potential (LBBp) was recorded or not, the patients were divided into the potential positive group (LBBAP+) and the potential negative group (LBBAP-). Electrocardiographic and echocardiographic parameters were used to evaluate electrical and mechanical characteristics. Lead parameters and complications were followed up. RESULTS: There were 52 patients in LBBAP+ and 18 patients in LBBAP-. The QRSd and the left ventricular activation time (LVAT) were wider after LBBAP. QRSd showed no significant difference between LBBAP+ and LBBAP-. LVAT was significantly shorter in LBBAP+ than in LBBAP-. Frontal QRS axis shifted leftward and the V1 morphologies changed after LBBAP. QRS axis and V1 morphologies showed no significant differences between two groups. Paced R-wave transition moved forward compared with intrinsic R-wave transition in both groups. Peak systolic strain of left ventricle (LVPSS) increased and peak systolic dispersion of left ventricle (LVPSD) did not change significantly after LBBAP. Systolic and diastolic function as well as mechanical synchronism had no significant differences between two groups. LBBAP had great pacing parameters. CONCLUSION: LBBAP changes electrical and mechanical characteristics and has good safety in patients with normal intrinsic QRSd. LBBAP+ and LBBAP- show no significant differences in mechanical synchronization and interventricular electrical synchronization. The LBBAP+ shows better left ventricular electrical synchronicity. This article is protected by copyright. All rights reserved.

13.
Clin Lung Cancer ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-33067127

RESUMO

BACKGROUND: There occurs huge heterogeneity in clinical outcomes for patients with epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). The purpose of this study was to indicate genetic biomarkers predicting primary resistance of EGFR-TKIs in these patients. PATIENTS AND METHODS: Using a next-generation sequencing panel with 168 cancer-related genes, matched tumor biopsy and plasma samples before treatments from patients with NSCLC were analyzed. Patients taking EGFR-TKIs were followed-up with imaging examination. Correlation of co-alterative genes with progression-free survival (PFS) was analyzed. RESULTS: Of the 48 patients treated with EGFR-TKIs, 46 (95.83%) had at least 1 genetic co-variant beyond EGFR mutation. Multivariate analysis indicated that RB1, PIK3CA, and ERBB2 co-alterations, rather than number of co-alterative genes, were independently associated with poorer PFS. Grouping patients by specific gene status showed best likelihood ratio χ2, Akaike information criterion, and Harrell concordance index. The median PFS for patients in group A (less genetic co-variations and wild specific genes), group B (more genetic co-variations and wild specific genes), group C (less genetic co-variations and altered specific genes), and group D (more genetic co-variations and altered specific genes) were 10.4, 9.13 (vs. group A; P = .3112), 6.33 (vs. group B; P = .0465), and 3.90 (vs. group C; P = .0309) months, respectively. CONCLUSIONS: This study revealed a high concomitant genetic alteration rate in patients with EGFR-mutated NSCLC. Specific gene variants were more important than number of altered genes in predicting poor PFS, and may help select patients needing new treatment strategies.

14.
Int J Spine Surg ; 14(4): 462-475, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32986565

RESUMO

BACKGROUND: Cervical spondylotic myelopathy is a neuromotor disorder responsible for functional limitations and decreased daily activities. Expansive open-door laminoplasty is the widely accepted procedure for the treatment of multilevel cervical spondylotic myelopathy. Among the various fixation procedures to secure the open lamina, miniplate fixation provides better clinical and radiological outcomes. However, the immediate effects on hinge fracture and hinge fracture displacement following miniplate fixation have not been proven until now. The purpose of our study was to elucidate the impact of cervical open-door angle on the status of spinal cord expansion and hinge fracture, hinge fracture displacement, and the role of implants used during surgery. METHODS: For this retrospective study, 122 patients who had undergone surgery from September 2016 to November 2017 with preoperative and postoperative radiographs were enrolled. Clinical and radiological outcomes were assessed before and after surgery. RESULTS: There were no significant differences in demographics, surgery time, blood loss, medical comorbidities, or perioperative and postoperative complications between 2 groups. The recovery rate and Nurick score before and at the follow-up show no statistical significance between the 2 groups, P value > .05 (P = .672) and P > .05 (P = .553), respectively. The statistical analysis shows that the mean hinge fracture in the miniplate group with a cervical open angle >30° was 2.42 ± 1.68 and with a <30° open angle, 0.05 ± 0.23; whereas, in the anchor group the mean hinge fracture in >30° cervical open angle was 2.227 ± 2.50 and in <30° was 0.409 ± 0.503. The results revealed statistical significance between 2 implant groups, P = .024 in the aspect of hinge fracture displacement and implant used. CONCLUSION: Laminoplasty by titanium miniplate fixation holds the laminae securely, prevents hinge fracture displacement, and promotes spinal cord expansion better than suture anchor fixation.

15.
Oncol Lett ; 20(5): 159, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32934727

RESUMO

Bioinformatics analyses have shown that transmembrane and coiled-coil domain 1 (TMCO1) may be associated with lung adenocarcinoma. However, to the best of our knowledge, no current research has determined whether TMCO1 is involved in the development of lung adenocarcinoma. The present study aimed to identify the association between TMCO1 and lung adenocarcinoma. The present study demonstrated that the positive immunohistochemical staining of TMCO1 in lung adenocarcinoma tissues was significantly higher compared with paracarcinoma tissues. Additionally, knockdown of TMCO1 was demonstrated to downregulate B-cell lymphoma-2 protein expression levels and upregulate cysteinyl aspartate specific proteinase (caspase)-3 and caspase-9 protein expression levels in A549 cells. These changes resulted in decreased apoptosis of A549 cells uponTMCO1 downregulation. In addition, knockdown of TMCO1 decreased matrix metalloproteinase (MMP)-2 and MMP-9 expression levels. The expression of N-cadherin and vimentin also decreased. By contrast, the expression levels of E-cadherin protein increased. Knockdown of TMCO1 resulted in the inhibition of A549 cell migration. The results of the present study demonstrated that TMCO1 was associated with lung adenocarcinoma and that inhibition of TMCO1 expression levels negatively regulated the apoptosis and migration of lung adenocarcinoma cells. Therefore, the present study suggests the potential for TMCO1 to be used in the clinical treatment of lung adenocarcinoma.

16.
Appl Opt ; 59(25): 7630-7637, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32902463

RESUMO

We propose a compact catadioptric imaging system based on even aspheric elements to solve some major limitations of conventional panoramic structure, such as field of view, blind spot, resolution, illumination, and less structure is introduced. The design includes a catadioptric front unit that is capable of providing a compression image of a panoramic scene and of relaying high-performance aspheric lenses to a decompression image. It is arranged to project two uncompressed images from two channels on a single sensor. Their optical paths do not interfere with each other, and there is no blind-spot image.

17.
J Immunother Cancer ; 8(2)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32948650

RESUMO

BACKGROUND: Accumulating evidence has shown that tumor-associated macrophages (TAMs) play a critical role in tumor progression. Targeting TAMs is a potential strategy for tumor immunotherapy. However, the mechanism underlying the TAM phenotype and function needs to be resolved. Our previous studies have demonstrated that miR-125a can reverse the TAM phenotype toward antitumor. Meanwhile, we have found that miR-125a and miR-99b cluster in the first intron of the same host gene, and are transcribed simultaneously in bone marrow-derived macrophages (BMDMs) following LPS+IFNγ stimulation. However, it remains unclear whether miR-99b by itself can exert an antitumor effect by regulating macrophage phenotype. METHODS: miR-99b and/or miR-125a were delivered into TAMs of orthotopic hepatocellular carcinoma (HCC) or subcutaneous Lewis lung cancer (LLC) mice. The effect of treatment was evaluated by live imaging, TUNEL staining and survival tests. The phenotype of the immune cells was determined by qRT-PCR, ELISA, western blot and FACS. The capability of miR-99b-mediated macrophage phagocytosis and antigen presentation was detected by FACS and immunofluorescence staining. The underlying molecular mechanism was examined by qRT-PCR, reporter assay and western blot, and further verified in the tumor model. The expression of miR-99b and its target genes was determined in TAMs sorted from tumor and adjacent tissues in patients with liver cancer. RESULTS: Targeted delivery of miR-99b and/or miR-125a into TAMs significantly impeded the growth of HCC and LLC, especially after miR-99b delivery. More importantly, the delivery of miR-99b re-educated TAM toward antitumor phenotype with enhanced immune surveillance. Further investigation of mechanisms showed that macrophage-specific overexpression of miR-99b promoted M1 while suppressing M2 macrophage polarization by targeting κB-Ras2 and/or mTOR, respectively. miR-99b-overexpressed M1 macrophage was characterized by stronger capability of phagocytosis and antigen presentation. Additionally, delivery of simTOR or siκB-Ras2 into TAMs inhibited miR-99b antagomir-triggered tumor growth. Finally, miR-99b expression was lower in TAMs of patients with liver cancer than that in adjacent tissues, while the expression of κB-Ras2 and mTOR was reversed. CONCLUSIONS: Our results reveal the mechanism of miR-99b-mediated TAM phenotype, indicating that TAM-targeted delivery of miR-99b is a potential strategy for cancer immunotherapy.

18.
FASEB J ; 34(8): 11168-11184, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32638441

RESUMO

Macrophages in lung, including resident alveolar macrophages (AMs) and interstitial macrophages (IMs), and monocyte-derived macrophages, play important roles in pulmonary fibrosis (PF), but mechanisms underlying their differential regulation remain unclear. Recombination signal-binding protein Jκ (RBP-J)-mediated Notch signaling regulates macrophage development and phenotype. Here, using bleomycin-induced fibrosis model combined with myeloid-specific RBP-J disruption (RBP-JcKO ) mouse, we investigated the role of Notch signaling in macrophages during PF. Compared with the control, RBP-JcKO mice exhibited alleviated lung fibrosis as manifested by reduced collagen deposition and inflammation, and decreased TGF-ß production. FACS analysis suggested that decreased Ly6clo MHCIIhi AMs might make the major contribution to attenuated fibrogenesis in RBP-JcKO mice, probably by reduced inflammatory factor release and enhanced matrix metalloproteinases expression. Using clodronate-mediated macrophage depletion in RBP-JckO mice, we demonstrated that embryonic-derived AMs play negligible role in lung fibrosis, which was further supported by adoptive transfer experiments. Moreover, on CCR2 knockout background, the effect of RBP-J deficiency on fibrogenesis was not elicited, suggesting that Notch regulated monocyte-derived AMs. Co-culture experiment showed that monocyte-derived AMs from RBP-JcKO mice exhibit reduced myofibroblast activation due to decreased TGF-ß secretion. In conclusion, monocyte-derived Ly6clo MHCIIhi AMs, which are regulated by RBP-J-mediated Notch signaling, play an essential role in lung fibrosis.

19.
Opt Express ; 28(13): 19726-19739, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32672243

RESUMO

The non-perfect determined amplitude distribution in the pupil would affect the convergence speed and accuracy of phase retrieval method, which depends on the amplitude of fields to reconstruct the phase. In this paper, we propose two kinds of phase retrieval methods based on hybrid point-polynomial and point-by-point nonlinear optimization algorithms to reconstruct simultaneously the amplitude and phase of the wavefront. Intensity quantized errors are avoided by using modified first derivatives. For simple and general wavefront testing, the accuracy and robustness of proposed algorithms are verified both numerically and experimentally.

20.
Mol Oncol ; 14(10): 2589-2608, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32679610

RESUMO

Cancer cells undergo epithelial-to-mesenchymal transition (EMT) in response to hypoxia. Exosomes produced in tumor microenvironments carry microRNAs (miRNAs) that affect proliferation, metastasis, and EMT. Hypoxic regulation of EMT is associated with telomerase content and stability, but the underlying mechanisms remain unclear. We identified a targeting relationship between tumor-suppressing miR-1255b-5p and human telomerase reverse transcriptase (hTERT) via clinical screening of serum samples in colorectal cancer (CRC) patients. EMT suppression via exosomal miR-1255b-5p delivery was investigated by assessing hTERT expression, Wnt/ß-catenin signaling, and telomerase activity. We revealed that hypoxia directly affected exosomal miR-1255b-5p content, the delivery of which between CRC cells significantly impacted cell invasion, EMT-related protein expression, and telomerase stability. Specifically, miR-1255b-5p suppressed EMT by inhibiting Wnt/ß-catenin activation via hTERT inhibition. Hypoxia reduced exosomal miR-1255b-5p secretion by CRC cells, thereby increasing hTERT expression to enhance EMT and telomerase activity. In a mouse CRC model, hypoxic exosomes containing overexpressed miR-1255b-5p attenuated EMT, tumor progression, and liver metastasis. Our results suggest the antitumor role of miR-1255b-5p and its involvement in the regulation of hTERT-mediated EMT. We propose that miRNA-targeted regulation of telomerase is a promising therapeutic strategy for future CRC treatment.

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