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1.
Knee Surg Relat Res ; 36(1): 17, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576029

RESUMO

BACKGROUND: Predicting hamstring graft size preoperatively for anterior cruciate ligament (ACL) reconstruction is important for preempting an insufficient diameter in graft size intraoperatively, possibly leading to graft failure. While there are multiple published methods using magnetic resonance imaging (MRI) picture archiving and communication systems (PACS), most are not feasible and practical. Our study aims to (1) practically predict the ACL hamstring graft size in a numerically continuous manner using the preoperative MRI from any native MRI PACS system, (2) determine the degree of correlation between the predicted and actual graft size, and (3) determine the performance of our prediction method if we define an adequate actual graft size as ≥ 8 mm. METHODS: A retrospective review of 112 patients who underwent primary ACL reconstruction with quadrupled hamstring semitendinosus-gracilis grafts at a tertiary institution was conducted between January 2018 and December 2018. Graft diameter can be predicted in a numerically continuous manner as √[2*(AB + CD)], where A and B are the semitendinosus cross-sectional length and breath, respectively, and C and D are the gracilis cross-sectional length and breath, respectively. RESULTS: A moderately positive correlation exists between the predicted and actual graft diameter (r = 0.661 and p < .001). Our method yields a high specificity of 92.6% and a moderate sensitivity of 67.2% if we define an adequate actual graft size as ≥ 8 mm. An area under receiver-operating characteristic curve shows good discrimination (AUC = 0.856). CONCLUSIONS: We present a practical method to predict the ACL hamstring graft size with high specificity using preoperative MRI measurements.

2.
Medicina (Kaunas) ; 60(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38674227

RESUMO

Background: Chemotherapy-induced cardiac dysfunction (CIC) is a significant and concerning complication observed among cancer patients. Despite the demonstrated cardioprotective benefits of statins in various cardiovascular diseases, their effectiveness in mitigating CIC remains uncertain. Objective: This meta-analysis aims to comprehensively evaluate the potential cardioprotective role of statins in patients with CIC. Methods: A systematic literature search was conducted using PubMed, Embase, and Scopus databases to identify relevant articles published from inception until 10th May 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CIs). Results: This meta-analysis comprised nine studies involving a total of 5532 patients, with 1904 in the statin group and 3628 in the non-statin group. The pooled analysis of primary outcome shows that patients who did not receive statin suffer a greater decline in the LVEF after chemotherapy compared to those who receive statin (MD, 3.55 (95% CI: 1.04-6.05), p = 0.01). Likewise, we observed a significantly higher final mean LVEF among chemotherapy patients with statin compared to the non-statin group of patients (MD, 2.08 (95% CI: 0.86-3.30), p > 0.001). Additionally, there was a lower risk of incident heart failure in the statin group compared to the non-statin group of patients (OR, 0.41 (95% CI: 0.27-0.62), p < 0.001). Lastly, the change in the mean difference for LVEDV was not statistically significant between the statin and non-statin groups (MD, 1.55 (95% CI: -5.22-8.33), p = 0.65). Conclusion: Among patients of CIC, statin use has shown cardioprotective benefits by improving left ventricular function and reducing the risk of heart failure.


Assuntos
Antineoplásicos , Cardiotoxicidade , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/complicações
3.
Front Pharmacol ; 15: 1383580, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681203

RESUMO

Lung cancer is still one of the deadliest malignancies today, and most patients with advanced lung cancer pass away from disease progression that is uncontrollable by medications. Super-enhancers (SEs) are large clusters of enhancers in the genome's non-coding sequences that actively trigger transcription. Although SEs have just been identified over the past 10 years, their intricate structure and crucial role in determining cell identity and promoting tumorigenesis and progression are increasingly coming to light. Here, we review the structural composition of SEs, the auto-regulatory circuits, the control mechanisms of downstream genes and pathways, and the characterization of subgroups classified according to SEs in lung cancer. Additionally, we discuss the therapeutic targets, several small-molecule inhibitors, and available treatment options for SEs in lung cancer. Combination therapies have demonstrated considerable advantages in preclinical models, and we anticipate that these drugs will soon enter clinical studies and benefit patients.

4.
J Immunother ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38679823

RESUMO

With the development of immune checkpoints inhibitors (ICIs), immunotherapy has recently taken center stage in cancer treatment. Dendritic cells exert complicated and important functions in antitumor immunity. This study aims to construct a novel dendritic cell marker gene signature (DCMGS) to predict the prognosis and immunotherapy response of lung adenocarcinoma (LUAD). DC marker genes in LUAD were identified by analysis of single-cell RNA sequencing data. 6 genes (G0S2, KLF4, ALDH2, IER3, TXN, CD69) were screened as the most prognosis-related genes for constructing DCMGS on a training cohort from TCGA data set. Patients were divided into high-risk and low-risk groups by DCMGS risk score based on overall survival time. Then, the predictive ability of the risk model was validated in 6 independent cohorts. DCMGS was verified to be an independent prognostic factor in multivariate analysis. Furthermore, we performed pathway enrichment analysis to explore possible biological mechanisms of the powerful predictive ability of DCMGS, and immune cell infiltration landscape and inflammatory activities were exhibited to reflect the immune profile. Notably, we bridged DCMGS with expression of immune checkpoints and TCR/BCR repertoire diversity that can inflect immunotherapy response. Finally, the predictive ability of DCMGS in immunotherapy response was also validated by 2 cohorts that had received immunotherapy. As a result, the patients with lower DCMGS risk scores showed a better prognosis and immunotherapy response. In conclusion, DCMGS was suggested to be a promising prognostic indicator for LUAD and a desirable predictor for immunotherapy response.

5.
Am J Chin Med ; 52(2): 453-469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38490806

RESUMO

Doxorubicin (DOX) is a powerful anthracycline antineoplastic drug used to treat a wide spectrum of tumors. However, its clinical application is limited due to cardiotoxic side effects. Astragaloside IV (AS IV), one of the major compounds present in aqueous extracts of Astragalus membranaceus, possesses potent cardiovascular protective properties, but the underlying molecular mechanisms are unclear. Thus, the aim of this study was to investigate the effect of AS IV on DOX-induced cardiotoxicity (DIC). Our findings revealed that DOX induced pyroptosis through the caspase-1/gasdermin D (GSDMD) and caspase-3/gasdermin E (GSDME) pathways. AS IV treatment significantly improved the cardiac function and alleviated myocardial injury in DOX-exposed mice by regulating intestinal flora and inhibiting pyroptosis; markedly suppressed the levels of cleaved caspase-1, N-GSDMD, cleaved caspase-3, and N-GSDME; and reversed DOX-induced downregulation of silent information regulator 1 (SIRT1) and activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mice. The SIRT1 inhibitor EX527 significantly blocked the protective effects of AS IV. Collectively, our results suggest that AS IV protects against DIC by inhibiting pyroptosis through the SIRT1/NLRP3 pathway.


Assuntos
Miócitos Cardíacos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Saponinas , Triterpenos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/metabolismo , Caspase 3/metabolismo , Sirtuína 1/metabolismo , Gasderminas , Doxorrubicina/efeitos adversos , Caspase 1/metabolismo
6.
Parasites Hosts Dis ; 62(1): 53-63, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38443770

RESUMO

The intracellular parasite Babesia microti is among the most significant species causing human babesiosis and is an emerging threat to human health worldwide. Unravelling the pathogenic molecular mechanisms of babesiosis is crucial in developing new diagnostic and preventive methods. This study assessed how priming with B. microti surface antigen 1 (BHSA 1) and seroreactive antigen 5-1-1 (BHSA 5-1-1) mediate protection against B. microti infection. The results showed that 500 µg/ml rBMSA1 and rBMSA5-1-1 partially inhibited the invasion of B. microti in vitro by 42.0 ± 3.0%, and 48.0 ± 2.1%, respectively. Blood smears revealed that peak infection at 7 days post-infection (dpi) was 19.6%, 24.7%, and 46.7% in the rBMSA1, rBmSA5-1-1, compared to the control groups (healthy mice infected with B. microti only), respectively. Routine blood tests showed higher white blood cell, red blood cell counts, and haemoglobin levels in the 2 groups (BMSA1 and BMSA5 5-1-1) than in the infection control group at 0-28 dpi. Moreover, the 2 groups had higher serum interferon-γ, tumor necrosis factor-α and Interleukin-17A levels, and lower IL-10 levels than the infection control group throughout the study. These 2 potential vaccine candidate proteins partially inhibit in vitro and in vivo B. microti infection and enhance host immunological response against B. microti infection.


Assuntos
Babesia microti , Babesiose , Gastrópodes , Humanos , Animais , Camundongos , Antígenos de Superfície , Grupos Controle , Contagem de Eritrócitos
7.
Cell Prolif ; : e13619, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38444279

RESUMO

YT521-B homology (YTH) domain family (YTHDF) proteins serve as readers that directly recognise m6A modifications. In this study, we aim to probe the role of YTHDF1 in environmental carcinogen-induced malignant transformation of gastric cells and gastric cancer (GC) carcinogenesis. We established a long-term low-dose MNU-induced malignant transformation model in gastric epithelial cells. In vivo and in vitro experiments were conducted to validate the malignant phenotype and characterise the roles of YTHDF1 and its downstream genes in malignant transformation cells. Additionally, we explored downstream m6A modification targets of YTHDF1 using RNA-sequencing, RNA immunoprecipitation, and proteomics analyses, and conducted validation experiments in cell experiments and clinical samples. Long-term low-dose exposure of MNU converted normal Gges-1 cells into malignant cells. YTHDF1 mRNA and protein expression are increased in MNU-induced malignant cells (p<0.001). Meanwhile, YTHDF1 knockdown inhibits the malignant potential of MNU-treated cells (p<0.01). YTHDF1 knockdown specifically suppresses HSPH1 protein, but not RNA levels. RIP-qPCR validates HSPH1 is the target of YTHDF1 (p<0.01). HSPH1 knockdown impairs the malignant potential of MNU-induced transformed cells. The increased expression of the key regulatory factor YTHDF1 in MNU-induced gastric carcinogenesis affects malignant transformation and tumorigenesis by regulating the translation of downstream HSPH1. These findings provide new potential targets for preventing and treating environmental chemical-induced gastric carcinogenesis.

8.
Neurosurg Rev ; 47(1): 115, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38480550

RESUMO

OBJECTIVE: The study aimed to evaluate the short-term clinical efficacy of percutaneous full-endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) for lumbar degenerative diseases (LDD). METHODS: From July 2020 to July 2021, 93 patients who underwent single-level lumbar fusion procedure were retrospective analysis. The patients were divided into Endo-TLIF group and transforaminal lumbar interbody fusion (TLIF) group. General demographic and perioperative data were recorded, the clinical outcomes were evaluated using visual analogue scale (VAS) and oswestry disability index (ODI). The disk height (DH) was compared between the two groups. RESULTS: All of the surgical procedures were successfully completed, and the patients were followed for a minimum of 2 years. Intraoperative blood loss, drainage volume, time to independent ambulation and hospital length of stay in the Endo-TLIF group were significantly decreased in comparison with the open TLIF group (p < 0.05). The VAS for back pain on postoperative 7 day and ODI on postoperative 1 month were lower in the Endo-TLIF group than in the open TLIF group (P < 0.05), but no significant difference at 1 year and 2 years postoperatively (P > 0.05). The VAS score of leg pain had no demographic statistically significant differences between the groups (P > 0.05). The DH were significantly heightened after surgery compared to the preoperative height (p < 0.05). CONCLUSION: Endo-TLIF is a minimally invasive, safety surgery which can achieve comparable short-term effects as open TLIF. It may be a promising option for the treatment of LDD.


Assuntos
Vértebras Lombares , Fusão Vertebral , Humanos , Estudos Retrospectivos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Endoscopia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento
9.
Nanoscale ; 16(13): 6708-6719, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38488127

RESUMO

Hypertrophic scar (HS) is characterized by an abnormal fibroblast-myofibroblast transformation; non-apoptosis of fibroblasts; and redundant expression of TGF-ß1, VEGF, α-SMA, and collagen I/III. An HS affects patients' physical and psychological quality of life, leading to joint dysfunction and skin cancer. However, there is currently no satisfactory drug to treat this disorder. In this study, we constructed methylprednisolone sodium succinate (MPSS) encapsulated ZIF-90 (MPSS@ZIF-90) for the effective treatment of an HS. The encapsulation of MPSS in ZIF-90 can achieve the controllable drug release of MPSS and prolong its effective treatment time. MPSS@ZIF-90 enhanced the apoptosis of human hypertrophic scar fibroblasts and downregulated the overexpression of TGF-ß1, VEGF, α-SMA, and collagen I/III both in vitro and in vivo. The instant injection of MPSS@ZIF-90 effectively intervened with the formation of the HS after 28 days. On the contrary, MPSS@ZIF-90 greatly reduced the HS with two injections and 14 days of treatment after the HS was formed. This work provides evidence of effective intervention in the formation of an HS and the therapeutic effectiveness of MPSS@ZIF-90 with short treatment periods in vivo. It suggests that MPSS@ZIF-90 can be used as a biomedical option in the treatment of skin wounds and may reveal the potential molecular basis for promising future antifibrotic agents against scarring.


Assuntos
Cicatriz Hipertrófica , Estruturas Metalorgânicas , Nanopartículas , Humanos , Cicatriz Hipertrófica/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/uso terapêutico , Hemissuccinato de Metilprednisolona/metabolismo , Hemissuccinato de Metilprednisolona/farmacologia , Hemissuccinato de Metilprednisolona/uso terapêutico , Qualidade de Vida , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fibroblastos/metabolismo , Colágeno Tipo I
10.
Turk J Gastroenterol ; 35(1): 48-60, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38454277

RESUMO

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma is the tumor type with the highest incidence of perineural invasion. This study tries to identify the differentially expressed genes regulated between pancreatic ductal adenocarcinoma tissues with perineural invasion and without perineural invasion. MATERIALS AND METHODS: The GSE102238 profile was downloaded. Gene function and pathway analysis were subsequently conducted. A protein-protein interaction network was constructed to search for hub genes. Both univariate Cox analysis and multivariate Cox analysis were calculated to identify prognostic factors. Quantitative real-time polymerase chain reaction (RT-PCR) and overall survival analysis of hub genes were used to verify. RESULTS: Our study identified 242 differentially expressed genes including 68 upregulated differentially expressed genes and 174 downregulated differentially expressed genes, which were involved in important functions and pathways. Nine relevant core genes using protein-protein interaction analysis as well as nestin (NES)/vascular endothlial growth factor (VEGF) signaling pathway which is highly related to the pathological process of perineural invasion in pancreatic ductal adenocarcinoma were also discovered. The differentiation was identified as an independent prognostic factor (P < .05) after multivariate Cox analysis. Three upregulated genes (JUP, CALM1, and NES) and 6 downregulated genes (EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3) were validated by quantitative RT-PCR and they all had markedly worse overall survival (P < .05). CONCLUSION: This analysis showed that 9 core genes including JUP, CALM1, NES, EPHA2, ARF1, ORM2, TERT, IL18, and CXCL3, as well as NES/VEGF signaling pathway, have a relationship with the development process of perineural invasion in pancreatic ductal adenocarcinoma. Cox analysis and overall survival analysis suggested differentiation as an independent prognostic factor and key roles for these 9 hub genes in perineural invasion prognosis in pancreatic ductal adenocarcinoma.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Interleucina-18/genética , Fator A de Crescimento do Endotélio Vascular/genética , Biomarcadores Tumorais/genética , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Prognóstico , Proto-Oncogenes , Expressão Gênica
11.
Int J Surg ; 110(4): 2421-2429, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38320107

RESUMO

BACKGROUND: Chronic steroid (CS) therapy was reportedly linked to increased vascular complications following percutaneous coronary intervention. However, its association with vascular complications after transcatheter aortic valve replacement (TAVR) remained uncertain, with conflicting results being reported. OBJECTIVE: The authors aimed to compare the rate of vascular complications and outcomes between patients with and without CS use after TAVR. METHODS: The authors conducted a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until 18th April 2022 for relevant studies. Endpoints were described according to Valve Academic Research Consortium-2 definitions. Effect sizes were pooled using DerSimonian and Laird random-effects model as risk ratio (RR) with 95% CI. RESULTS: Five studies with 6136 patients undergoing TAVR were included in the analysis. The included studies were published between 2015 and 2022. The mean ages of patients in both study groups were similar, with the CS group averaging 80 years and the nonsteroid group averaging 82 years. Notably, a higher proportion of patients in the CS group were female (56%) compared to the nonsteroid group (54%). CS use was associated with a significantly higher risk of major vascular complications (12.5 vs. 6.7%, RR 2.32, 95% CI: 1.73-3.11, P <0.001), major bleeding (16.8 vs. 13.1%, RR 1.61, 95% CI: 1.27-2.05, P <0.001), and aortic annulus rupture (2.3 vs. 0.6%, RR 4.66, 95% CI: 1.67-13.01, P <0.001). There was no significant difference in terms of minor vascular complications (RR 1.43, 95% CI: 1.00-2.04, P =0.05), in-hospital mortality (2.3 vs. 1.4%, RR 1.86, 95% CI: 0.74-4.70, P =0.19), and 30-day mortality (2.9 vs. 3.1%, RR 1.14, 95% CI: 0.53-2.46, P =0.74) between both groups. CONCLUSION: Our study showed that CS therapy is associated with increased major vascular complications, major bleeding, and annulus rupture following TAVR. Further large multicenter studies or randomized controlled trials are warranted to validate these findings.


Assuntos
Complicações Pós-Operatórias , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estenose da Valva Aórtica/cirurgia , Esteroides/efeitos adversos , Esteroides/administração & dosagem , Doenças Vasculares/etiologia , Doenças Vasculares/epidemiologia , Feminino , Idoso de 80 Anos ou mais , Masculino
12.
Heliyon ; 10(2): e24560, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304808

RESUMO

Purpose: To evaluate the ability of computer-aided diagnosis (CAD) system (S-Detect) to identify malignancy in ultrasound (US) -detected BI-RADS 3 breast lesions. Materials and methods: 148 patients with 148 breast lesions categorized as BI-RADS 3 were included in the study between January 2021 and September 2022. The malignancy rate, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were calculated. Results: In this study, 143 breast lesions were found to be benign, and 5 breast lesions were malignant (malignancy rate, 3.4 %, 95 % confidence interval (CI): 0.5-6.3). The malignancy rate rose significantly to 18.2 % (4/22, 95 % CI: 2.1-34.3) in the high-risk group with a "possibly malignant" CAD result (p = 0.017). With a "possibly benign" CAD result, the malignancy rate decreased to 0.8 % (1/126, 95 % CI: 0-2.2) in the low-risk group (p = 0.297). The AUC, sensitivity, specificity, accuracy, PPV, and NPV of the CAD system in BI-RADS 3 breast lesions were 0.837 (95 % CI: 77.7-89.6), 80.0 % (95 % CI: 73.6-86.4), 87.4 % (95 % CI: 82.0-92.7), 87.2 % (95 % CI: 81.8-92.6), 18.2 % (95 % CI: 2.1-34.3) and 99.2 % (95 % CI: 97.8-100.0), respectively. Conclusions: CAD system (S-Detect) enables radiologists to distinguish a high-risk group and a low-risk group among US-detected BI-RADS 3 breast lesions, so that patients in the low-risk group can receive follow-up without anxiety, while those in the high-risk group with a significantly increased malignancy rate should actively receive biopsy to avoid delayed diagnosis of breast cancer.

13.
J Adv Res ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38341031

RESUMO

INTRODUCTION: The long-term overuse of malachite green (MG) has potential carcinogenic, teratogenic, and mutagenic effects. The functional nanocomposite is novel and challenging to construct and implement through surface enhanced Raman scattering (SERS) strategy to reveal the contributions in application. OBJECTIVES: The novel Ag-CDs (carbon dots)-PBA (phenyl boric acid) nanocomposite was constructed by a facile route to detect toxic MG molecule with high SERS sensitivity and good uniformity. METHODS: The enhanced substrate used for the detection of MG has been successfully constructed using PBA modulated Ag-CDs on a structured surface with rich binding sites. RESULTS: The fabricated Ag-CDs-PBA substrate can be used to analyze various probe molecules exhibiting high sensitivity, good signal reproducibility, and excellent stability. The mechanism between components has been proved by calculations originating from the plasmonic Ag and active electronic transmission among the bridging CDs and PBA via the close spatial π-π effect. In addition, the accelerated separation of electron-hole pairs was triggered to further improve the SERS activity of the hybrid via a bidirectional charge transfer (CT) process. Significantly, the Ag-CDs-PBA system shows distinctive selectivity, in which PBA can hinder the interference of other species without specific hydroxyl groups. CONCLUSION: Based on this deeper insight on plasmon-mediated mechanism, the SERS substrate was successfully practiced for quantitative determination in real water and fish samples. The strategy developed promises to be a new sensor technology and has great potential for environmental and food safety applications.

14.
Arab J Gastroenterol ; 25(1): 42-50, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38220481

RESUMO

BACKGROUND AND STUDY AIMS: MicroRNA (miRNA) is involved in diverse biological and physiological processes of tumors. Dysregulation of miRNA will induce a series of human diseases. miR-129-2-3p has vital effects in the pathogenesis of various tumors. However, the regulatory function of miR-129-2-3p in colon cancer remains to be clarified. This study investigated the role of miR-129-2-3p targeting BZW1 in proliferation, apoptosis, migration, and invasion of colon cancer. PATIENTS AND METHODS: Here, RT-qPCR was applied to measure the miR-129-2-3p levels in colon cancer tissues. The predicted targets of miR-129-2-3p were identified by bioinformatics and verified using luciferase reporter assay. The effects of miR-129-2-3p on colon cancer were detected by CCK-8, colony formation, transwell chamber test, wound healing, and flow cytometry assays. Finally, the influence of miR-129-2-3p on tumor growth was studied. Nude mice were xenografted with transfected Lovo cells by subcutaneous injection of 5 × 105 cells in 100 µl. HE staining and TUNEL were used to assess metastasis ability. RESULTS: miR-129-2-3p level in colon cancer tissue was significantly reduced. Furthermore, it was verified that BZW1 was a target of miR-129-2-3p, and its expression in colon cancer cells was inhibited by miR-129-2-3p. Additionally, miR-129-2-3p inhibited colon cancer cell proliferation, colony formation, mobility ability and tumor growth, and promoted cell apoptosis by targeting BZW1. miR-129-2-3p overexpression in tumor xenografts in vivo decreased BZW1 expression, and suppressed tumor growth. CONCLUSION: Collectively, these findings indicated that miR-129-2-3p exerts a suppressive role in colon cancer cells by directly targeting BZW1, and may have significant therapeutic implications for patients with colon cancer.


Assuntos
Neoplasias do Colo , MicroRNAs , Animais , Camundongos , Humanos , Camundongos Nus , Linhagem Celular Tumoral , MicroRNAs/genética , Proliferação de Células/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo
15.
J Gene Med ; 26(1): e3624, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38087999

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has poor survival. Effective prognostic models with high application value remain lack. METHODS: Bulk RNA seq and single cell RNA-seq data were retrieved from the XENA-TCGA-ESCC cohort and GSE188900. The anoikis-related gene score (ANO score) model and tumor microenvironment score (TME score) model were constructed and merged into three subgroups. Functional annotation was analyzed by Gene Ontology terms. Univariate and multivariate Cox regression analysis, least absolute shrinkage and selection operator regression analysis and weighted gene coexpression network analysis were performed to construct prognostic prediction models and identify prognostic value. Kaplan-Meier survival curves were drawn for evaluating the overall survival (OS) of patients classified by different score subgroups. Immunotherapy response and mutation analyses were also conducted. RESULTS: In the ANO score model, TNFSF10 was an independent factor for the prognosis of ESCC patients. The area under the curve values of the ANO-TME score model in predicting the OS were 0.638 at 5 years and 0.632 at 7 years. Patients in the ANO low score-TME high score group had a much longer OS than patients in any other ANO-TME score subgroup (p < 0.001), suggesting a higher prognostic value. The differentially expressed genes of the ANO low score-TME high score group were mainly involved in cell adhesion molecules, nucleotide excision repair, the TGF-ß signaling pathway and mismatch repair. TP53 (92%), TTN (38%) and NFE2L2 (31%) were the top genes with highest mutant frequency in the ANO low score-TME high score group. CONCLUSIONS: A novel prognostic prediction model with high application value was constructed and identified for ESCC patients, which may provide evidence for immunotherapy in the treatment of ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Prognóstico , Anoikis/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Microambiente Tumoral/genética
16.
Eur Spine J ; 33(2): 409-416, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37378709

RESUMO

PURPOSE: To investigate the clinical results and radiological parameters changes after unilateral-approach endoscopic lumbar interbody fusion (Endo-LIF) for lumbar spondylolisthesis with bilateral symptoms. METHODS: 43 single-level lumbar spondylolisthesis patients with bilateral lower limb symptoms were included from June 2020 to May 2022. All patients underwent unilateral-approach Endo-LIF and postoperative computed tomography. Radiological parameters including disk height (DH), degree of upper vertebral slip (DUVS), and foramen intervertebral parameters including bilateral foraminal height (FH), contralateral foraminal areas (FA) were evaluated. The clinical outcomes including low back pain and bilateral leg pain were evaluated using Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI) before and after surgery. RESULTS: All cases were successfully completed surgery and followed for average 15.16 ± 5.2 months. DH (44% ± 11%) and DUVS were significantly improvement postoperatively compared with preoperatively (p < 0.05). Statistically significant increases in bilateral FH (25% ± 11% on the surgical side, 17% ± 8% on the contralateral side) and contralateral FA (26% ± 6%) were observed (p < 0.05). The VAS and the ODI scores were significantly decreased in comparison with the preoperative scores (p < 0.05). CONCLUSION: Unilateral-approach with contralateral indirect decompression in Endo-LIF can acquire satisfactory clinical outcomes. Therefore, unilateral-approach Endo-LIF may be a promising option for lumbar spondylolisthesis with bilateral symptoms.


Assuntos
Dor Lombar , Espondilolistese , Humanos , Espondilolistese/complicações , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia , Endoscopia , Região Lombossacral , Dor Lombar/diagnóstico por imagem , Dor Lombar/etiologia , Dor Lombar/cirurgia , Tomografia Computadorizada por Raios X
17.
J Gene Med ; 26(1): e3573, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37547956

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD), as the most common type of lung cancer, poses a significant threat to public health. Tumor heterogeneity plays a crucial role in carcinogenesis, which could be largely deciphered by next-generation sequencing (NGS). METHODS: We obtained and screened single-cell RNA sequencing (scRNA-seq) data from 16 LUAD samples, and endothelial cells (ECs) were grouped into three clusters. The origin of EC differentiation was explored by pseudo-time analysis. CellChat analysis was used to detect potential communication between ECs and malignant cells, and gene regulatory network analysis was used to identify changes in transcription factor activity. We explored the prognosis of specific ECs clusters and their effects on the tumor microenvironment (TME) at the bulk transcriptome level. 5-Ethynyl-2'- deoxyuridine (EdU) and Ki-67 staining were conducted to study the proliferative phenotype of LUAD cell lines. Western blotting targeting the phosphorylation of PI3K-AKT proteins was utilized for determination of the downstream pathway of NCL. RESULTS: COL3A1-positive ECs showed the highest crosstalk interaction with malignant cells, indicating that they have important effects on driving LUAD carcinogenesis. Vascular endothelial growth factor (VEGF) signaling pathway was identified as the main signaling pathway, mediating signal transduction from malignant cells. The TME-related genes of COL3A1-positive ECs were significantly more highly expressed. COL3A1-positive ECs showed unique metabolic and immune characteristics, as well as highly activated metabolic signaling pathways and inflammatory responses. Importantly, LUAD patients with low COL3A1-positive ECs scores displayed an inferior prognosis outcome and a higher risk of metastasis. The key target gene NCL, which is involved in the interaction between epithelial cells and cancer cells, has been identified through screening. Flow cytometry showed that knockdown of NCL prompted the apoptosis of A549 and NCI-H1299. Western blotting showed that knockdown of NCL decreased the phosphorylation of AKT and PI3K, which identified the downstream pathway of NCL. CONCLUSIONS: COL3A1-positive ECs have important effects on the development of LUAD and the formation of an immune microenvironment. Furthermore, we identified a key target gene, NCL, which is involved in the interaction between endothelial cells and cancer cells. NCL also affected the apoptosis and proliferation in LUAD through the PI3K-AKT pathway.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Fator A de Crescimento do Endotélio Vascular , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Carcinogênese/genética , Proliferação de Células/genética , Microambiente Tumoral/genética , Colágeno Tipo III
18.
Talanta ; 270: 125554, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38150967

RESUMO

Assessing the total antioxidant capacity (TAC) of foods plays a significant role in dietary guidance and disease risk reduction. Therefore, building a simple, rapid, and sensitive sensing method for detecting TAC possesses broad application prospects. Herein, we constructed a novel nanozyme catalyzed‒surface-enhanced Raman resonance scattering (SERRS) sensing strategy for analysis of TAC based on polyvinylpyrrolidone coated gold nanoparticles (AuNPs@PVP) that was synthesized by one step reduction method. AuNPs@PVP not only served as the SERRS substrate but also possessed high oxidase activity which can catalyze 3,3',5,5'-tetramethylbenzidine (TMB) oxidation by generating hydroxyl radicals (•OH) and superoxide anion free radical (•O2-). According to the inhibiting effect of antioxidants, ascorbic acid (AA) was selected as the representative for TAC detection. The linear range and limit of detection (LOD) were determined to be 10-8‒10-5 M and 0.6 nM, respectively. More importantly, the proposed nanozyme catalyzed‒SERRS strategy has been successfully applied to the detection of TAC in fruit juices, demonstrating promising potential in the field of food supervision and healthcare applications.


Assuntos
Antioxidantes , Nanopartículas Metálicas , Antioxidantes/análise , Oxirredutases , Ouro , Oxirredução , Colorimetria/métodos , Peróxido de Hidrogênio/análise
19.
Curr Probl Cardiol ; 49(1 Pt C): 102098, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37734695

RESUMO

Congenital heart disease (CHD), the most prevalent congenital disorder in newborns, is a leading cause of infant mortality. Mortality rates have declined over time with advancements in knowledge and management approaches. Despite these advancements, studies on racial disparities in CHD surgical mortality have yielded inconclusive results. We aim to evaluate the disparity among the clinical outcomes post-CHD surgery. A comprehensive literature search was conducted on PubMed, Embase, and Scopus utilizing predefined MeSH terms coupled with Boolean operators "AND" and "OR." The search strategy included the terms "congenital heart disease" AND "racial disparity" OR "minorities" OR "Black" OR "White" AND "mortality." Our meta-analysis sought observational studies published from inception until 10th March 2023 reporting post-surgical incidence of mortality in Black and White patients with CHD. We identified 5 studies, including 79616 patients with CHD. Of these, 15,124 Black patients and 64,492 White patients who underwent for CHD surgery. All included patients were less than 18 years of age with a definitive diagnosis of CHD. The mean length of the hospital stay was (11.5 vs 10.10) days, respectively. The pooled analysis showed that Black patients with CHD have significantly higher odds of postoperative mortality (OR, 1.46 (95%CI: 1.31-1.62), P < 0.001) with low heterogeneity across the studies. This very first meta-analysis shows that Black patients are at increased risk of mortality post-CHD surgery compared to White patients. These disparities need to be addressed, and proper guidelines need to be made with better medical infrastructure and treatment options for racial minority groups.


Assuntos
Disparidades em Assistência à Saúde , Cardiopatias Congênitas , Grupos Raciais , Humanos , Lactente , Recém-Nascido , População Negra , Cardiopatias Congênitas/cirurgia , Incidência , Tempo de Internação , Estudos Observacionais como Assunto , População Branca
20.
World J Surg ; 47(12): 3205-3213, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37805926

RESUMO

OBJECTIVES: Ultrasound tends to present very high sensitivity but relatively low specificity and positive predictive value (PPV), which would result in unnecessary breast biopsies. The purpose of this study is to analyze the diagnostic performance of computer-aided diagnosis (CAD) (S-Detect) system in differentiating breast lesions and reducing unnecessary biopsies in non-university hospitals in less-developed regions of China. METHODS: The study was a prospective multicenter study from 8 hospitals. The ultrasound images, and cine, CAD analysis, and BI-RADS were recorded. The accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the curve (AUC) were analyzed and compared between CAD and radiologists. The Youden Index (YI) was used to determine optimal cut-off for the number of planes to downgrade. RESULTS: A total of 491 breast lesions were included in the study. Less-experienced radiologists combined CAD was superior to less-experienced radiologists alone in AUC (0.878 vs 0.712, p < 0.001), and specificity (81.3% vs 44.6%, p < 0.001). There was no statistical difference in AUC (0.891 vs 0.878, p = 0.346), and specificity (82.3% vs 81.3%, p = 0.791) between experienced radiologists and less-experienced radiologists combined CAD. With CAD assistance, the biopsy rate of less-experienced radiologists was significantly decreased (100.0% vs 25.6%, p < 0.001), and malignant rate of biopsy was significantly increased (15.0% vs 43.9%, p < 0.001). CONCLUSIONS: CAD system can be an effective auxiliary tool in differentiating breast lesions and reducing unnecessary biopsies for radiologists from non-university hospitals in less-developed regions of China.


Assuntos
Neoplasias da Mama , Ultrassonografia Mamária , Feminino , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia Mamária/métodos , Diagnóstico por Computador/métodos , Computadores , Neoplasias da Mama/diagnóstico por imagem
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