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1.
Cell Rep ; 43(4): 114049, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38573853

RESUMO

Heterotopic ossification (HO) is a challenging condition that occurs after musculoskeletal injury and is characterized by the formation of bone in non-skeletal tissues. While the effect of HO on blood vessels is well established, little is known about its impact on lymphatic vessels. Here, we use a mouse model of traumatic HO to investigate the relationship between HO and lymphatic vessels. We show that injury triggers lymphangiogenesis at the injury site, which is associated with elevated vascular endothelial growth factor C (VEGF-C) levels. Through single-cell transcriptomic analyses, we identify mesenchymal progenitor cells and tenocytes as sources of Vegfc. We demonstrate by lineage tracing that Vegfc-expressing cells undergo osteochondral differentiation and contribute to the formation of HO. Last, we show that Vegfc haploinsufficiency results in a nearly 50% reduction in lymphangiogenesis and HO formation. These findings shed light on the complex mechanisms underlying HO formation and its impact on lymphatic vessels.

2.
Angew Chem Int Ed Engl ; : e202405197, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38574245

RESUMO

Mammalian cytochrome P450 drug-metabolizing enzymes rarely cleave carbon-carbon (C-C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual cleavages of non-polar, unstrained C(sp2)-C(sp3) bonds in the FDA-approved tyrosine kinase inhibitor pexidartinib that are mediated by CYP3A4/5, the major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out the Baeyer-Villiger oxidation mechanism that is commonly invoked to address P450-mediated C-C bond cleavages. Our studies in 18O2 and H218O enriched systems reveal two unusual distinct mechanisms of C-C bond cleavage: one bond is cleaved by CYP3A-mediated ipso-addition of oxygen to a C(sp2) site of N-protected pyridin-2-amines, and the other occurs by a pseudo-retro-aldol reaction after hydroxylation of a C(sp3) site. This is the first report of CYP3A-mediated C-C bond cleavage in drug metabolism via ipso-addition of oxygen mediated mechanism. CYP3A-mediated ipso-addition is also implicated in the regioselective C-C cleavages of several pexidartinib analogs. The regiospecificity of CYP3A-catalyzed oxygen ipso-addition under environmentally friendly conditions may be attractive and inspire biomimetic or P450-engineering methods to address the challenging task of C-C bond cleavages.

3.
Front Microbiol ; 15: 1379341, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596374

RESUMO

The objective of this study is to optimize the ultrasonic-assisted extraction process of Ku Shen (Sophorae Flavescentis Radix) extracts (KSE) against Vibrio parahaemolyticus and explore their anti-biofilm activity and mechanism of action. The ultrasonic-assisted extraction process of KSE optimized by single factor experiment, Box-Behnken design and response surface methodology was as follows: 93% ethanol as solvent, liquid/material ratio of 30 mL/g, ultrasonic power of 500 W, extraction temperature of 80°C and time of 30 min. Under these conditions, the diameter of inhibition circle of KSE was 15.60 ± 0.17 mm, which had no significant difference with the predicted value. The yield of dried KSE is 32.32 ± 0.57% and the content of total flavonoids in KSE was 57.02 ± 5.54%. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of KSE against V. parahaemolyticus were 0.25 and 0.5 mg/mL, respectively. Crystal violet staining, Congo red plate, spectrophotometry, CCK-8 and scanning electron microscopy were used to investigate the activity and mechanism of action of KSE against V. parahaemolyticus biofilm. The results showed that the sub-MIC of KSE could significantly inhibit biofilm formation, reduce the synthesis of polysaccharide intercellular adhesin (PIA) and the secretion of extracellular DNA. In addition, the inhibition rate of biofilm formation and clearance rate of mature biofilm of 1.0 mg/mL KSE were 85.32 and 74.04%, and the reduction rate of metabolic activity of developing and mature biofilm were 77.98 and 74.46%, respectively. These results were confirmed by visual images obtained by scanning electron microscopy. Therefore, KSE has the potential to further isolate the anti-biofilm agent and evaluate it for the preservation process of aquatic products.

4.
Arch Toxicol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630283

RESUMO

Cannabidiol (CBD), one of the major components extracted from the plant Cannabis sativa L., has been used as a prescription drug to treat seizures in many countries. CBD-induced male reproductive toxicity has been reported in animal models; however, the underlying mechanisms remain unclear. We previously reported that CBD induced apoptosis in primary human Leydig cells, which constitute the primary steroidogenic cell population in the testicular interstitium. In this study, we investigated the effects of CBD and its metabolites on TM3 mouse Leydig cells. CBD, at concentrations below 30 µM, reduced cell viability, induced G1 cell cycle arrest, and inhibited DNA synthesis. CBD induced apoptosis after exposure to high concentrations (≥ 50 µM) for 24 h or a low concentration (20 µM) for 6 days. 7-Hydroxy-CBD and 7-carboxy-CBD, the main CBD metabolites of CBD, exhibited the similar toxic effects as CBD. In addition, we conducted a time-course mRNA-sequencing analysis in both primary human Leydig cells and TM3 mouse Leydig cells to understand and compare the mechanisms underlying CBD-induced cytotoxicity. mRNA-sequencing analysis of CBD-treated human and mouse Leydig cells over a 5-day time-course indicated similar responses in both cell types. Mitochondria and lysosome dysfunction, oxidative stress, and autophagy were the major enriched pathways in both cell types. Taken together, these findings demonstrate comparable toxic effects and underlying mechanisms in CBD-treated mouse and primary human Leydig cells.

5.
Opt Express ; 32(7): 11395-11405, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570988

RESUMO

In this paper, we propose a chaotic block-matching and three-dimensional (C-BM3D) filtering algorithm to remove the noise and enhance the security in the turbulent channel of free space optical (FSO) communication. We experimentally demonstrate the performance of C-BM3D by comparing it with chaotic non-local means filtering (C-NLM), chaotic Gaussian filtering and chaotic Median filtering based on Log-normal and Gamma-Gamma turbulence models. The results show that the peak signal-to-noise ratios (PSNRs) of C-BM3D in the weak turbulence under Log-normal and Gamma-Gamma models are up to 96.2956 and 93.2853, respectively. The C-BM3D also achieves superior image similarity in Log-normal turbulent channel, with its structural similarity index measures (SSIMs) nearly equal to 1. Additionally, the signal-to-noise ratio (SNR) of C-BM3D ranks the highest, and its bit error rate (BER) improves by at least 15 dB compared to that of the other three algorithms. The experimental results indicate that the C-BM3D can be a good candidate for the next generation of FSO communication in security and turbulence resistance.

6.
Comput Biol Med ; 174: 108219, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38581997

RESUMO

Lung cancer is a prevalent form of cancer worldwide, necessitating early and accurate diagnosis for successful treatment. Within medical imaging processing, image segmentation plays a vital role in medical diagnosis. This study applies swarm intelligence algorithms to segment lung cancer pathological images at three levels. The original algorithm incorporates the Whales' search prey mechanism and a random mutation strategy, resulting in an improved version named WDRIME, which aims to enhance convergence speed and avoid local optima (LO). Additionally, the study introduces a multilevel image segmentation method for lung cancer based on the improved algorithm. WDRIME's performance is showcased by comparing it to the state-of-the-art algorithms in IEEE CEC2014. To design a framework for lung cancer image segmentation, this paper combines the WDRIME algorithm with the multilevel segmentation method. Evaluation of the segmentation results employs metrics such as PSNR, SSIM, and FSIM. Overall, the analysis confirms that the proposed algorithm supersedes others regarding convergence speed and accuracy. This model signifies a high-quality segmentation method and offers practical support for in-depth exploration of lung cancer pathological images.

7.
J Adv Res ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38615741

RESUMO

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women with unfavorite prognosis. OBJECTIVES: Tanshinone IIA (Tan IIA) inhibits BC progression, however, the underlying mechanism remains largely undefined. METHODS: The cytotoxicity of Tan IIA was assessed by CCK-8 and LDH assays. Ferroptosis was monitored by the level of MDA, Fe2+, lipid ROS and GSH. IHC and western blot were employed to detect the localization and expression of SLC7A11, PIAS4, KDM1A and other key molecules. The SUMOylation of SLC7A11 was detected by Ni-beads pull-down assay and co-IP. Luciferase and ChIP assays were employed to detect the direct association between KDM1A and PIAS4 promoter. The proliferative and metastatic properties of BC cells were assessed by colony formation, CCK-8 and Transwell assays, respectively. The in vitro findings were verified in xenograft and lung metastasis models. RESULTS: Tan IIA promoted ferroptosis by suppressing SLC7A11 in BC cells. Silencing of PIAS4 or KDM1A inhibited cell growth and metastasis in BC. Mechanistically, PIAS4 facilitated the SUMOylation of SLC7A11 via direct binding to SLC7A11, and KDM1A acted as a transcriptional activator of PIAS4. Functional studies further revealed that Tan IIA decreased KDM1A expression, thus suppressing PIAS4 expression transcriptionally. The inhibition of PIAS4-dependent SUMOylation of SLC7A11 further induced ferroptosis, thereby inhibiting proliferation and metastasis in BC. CONCLUSION: Tan IIA promoted ferroptosis and inhibited tumor growth and metastasis via suppressing KDM1A/PIAS4/SLC7A11 axis.

8.
Plants (Basel) ; 13(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38592801

RESUMO

Mulching practices have been used to improve peach growth and production across the globe. However, the impact of mulching on the physiochemical properties and soil characteristics of orchards remains largely unknown. This study aimed to decipher the impacts of various mulching patterns on the soil environment and the quality of Prunus persica fruit in "Zijinhuangcui". Three treatments were set up, which included black ground fabric mulch (BF) and two living grass mulch treatments (HV: hairy vetch and RG: ryegrass). The results showed that different mulching treatments have different effects on soil, plant growth, and fruit quality. Living grass mulch treatments, especially the HV treatment, significantly improved soil nutrients by enhancing nitrogen-related indicators. Of note, the BF treatment had higher total phosphorus and available phosphorus contents than the HV and RG treatments. The HV treatment had the highest relative abundance of Proteobacteria (33.49%), which is associated with symbiotic nitrogen fixation, followed by RG (25.62%), and BF (22.38%) at the young fruit stage. Similarly, the abundance of Terrimonas, which has a unique nitrogen fixation system at the genus level, was significantly higher in the living grass mulch (HV, 1.30-3.13% and RG, 2.27-4.24%) than in the BF treatment. Living grass mulch also promoted tree growth, increased fruit sugar content, sugar-related components, and sugar-acid ratio, and reduced the acid content. Collectively, the findings of this study show that living grass mulch can promote tree growth and improve fruit quality by improving soil fertility, bacterial diversity, and richness.

9.
Aesthetic Plast Surg ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609659

RESUMO

INTRODUCTION: Hair transplantation surgery requires the efficient completion of hair follicles and thus appropriate hair implantation needles. The objectives of this study were to evaluate the effectiveness and feasibility of self-made hair implantation needles using injection needles and evaluate the speed of different hair implantation methods. METHODS: Four patients were randomly assigned to four groups. A gem knife pre-punching planting method was used for the patient in Group A, while Group B received immediate implantation after punching with ordinary injection needles, Group C was treated with synchronized punching and planting using hair implanters, and Group D was treated with a self-made hair implantation needle. The speed of the different implantation methods for single and double hair follicles and the differences between the planting of single and double hair follicles were assessed. RESULTS: Group D was found to have the fastest hair planting speed for both single and double hair follicles, followed by Groups C and A, with the slowest speed observed in Group B. Groups A and B were associated with significantly lower speeds of double hair planting than single hair planting, There was no significant difference between Groups C and D. CONCLUSIONS: The self-made hair implantation needle is a novel and efficient tool for synchronized punching and planting. It has a faster planting speed and does not require assistance. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

10.
ISA Trans ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38614899

RESUMO

We propose a reliability-based anti-disturbance control (RADC) method for systems with parametric stochastic uncertainty based on the linear matrix inequality (LMI) and the limit state function. Differing from the existing anti-disturbance control, the parametric stochastic uncertainty is considered in both the concerned system and the exogenous disturbance system. With this consideration, the condition for system stability and performance robustness is described by a stochastic LMI which holds with a certain probability (reliability). Through the limit state function method, the stochastic LMI is subtly transformed into two probabilistic LMIs for two different cases. The proposed probabilistic LMIs contain two probabilistic parameters of reliability indexes that quantify the effect of parametric stochastic uncertainty. At different prescribed reliability indexes, controllers with different reliability can be flexibly and reliably designed. Two illustrative examples with Monte-Carlo verification are presented to demonstrate the feasibility and effectiveness of the proposed RADC method.

11.
Elife ; 122024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635322

RESUMO

Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.


Assuntos
Encéfalo , Macaca , Animais , Humanos
12.
Mol Cancer Res ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647377

RESUMO

Wilms tumor, the most common pediatric kidney cancer, resembles embryonic renal progenitors. Currently, there are no ways to therapeutically target Wilms tumor driver mutations, such as in the microRNA processing gene DROSHA. Here we used a "multi-omics" approach to define the effects of DROSHA mutation in Wilms tumor. We categorized Wilms tumor mutations into four mutational subclasses with unique transcriptional effects: microRNA processing, MYCN activation, chromatin remodeling, and kidney developmental factors. In particular, we find that DROSHA mutations are correlated with de-repressing microRNA target genes that regulate differentiation and proliferation and a self-renewing, mesenchymal state. We model these findings by inhibiting DROSHA expression in a Wilms tumor cell line, which led to upregulation of the cell cycle regulator cyclin D2 (CCND2). Furthermore, we observed that DROSHA mutations in Wilms tumor and DROSHA silencing in vitro were associated with a mesenchymal state with aberrations in redox metabolism. Accordingly, we demonstrate that Wilms tumor cells lacking microRNAs are sensitized to ferroptotic cell death through inhibition of glutathione peroxidase 4 (GPX4), the enzyme that detoxifies lipid peroxides. Implications: This study reveals genotype-transcriptome relationships in Wilms tumor and points to ferroptosis as a potentially therapeutic vulnerability in one subset of Wilms tumor.

13.
Anal Chem ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38648202

RESUMO

Accurate detection of endogenous miRNA modifications, such as N6-methyladenosine (m6A), 7-methylguanosine (m7G), and 5-methylcytidine (m5C), poses significant challenges, resulting in considerable uncertainty regarding their presence in mature miRNAs. In this study, we demonstrate for the first time that liquid chromatography coupled with a tandem mass spectrometry (LC-MS/MS) nucleoside analysis method is a practical tool for quantitatively analyzing human miRNA modifications. The newly designed liquid-solid two-step hybridization (LSTH) strategy enhances specificity for miRNA purification, while LC-MS/MS offers robust capability in recognizing modifications and sufficient sensitivity with detection limits ranging from attomoles to low femtomoles. Therefore, it provides a more reliable approach compared to existing techniques for revealing modifications in endogenous miRNAs. With this approach, we characterized m6A, m7G, and m5C modifications in miR-21-5p, Let-7a/e-5p, and miR-10a-5p isolated from cultured cells and observed unexpectedly low abundance (<1% at each site) of these modifications.

14.
Fitoterapia ; 175: 105938, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38565379

RESUMO

Five new B-seco-limonoids, namely toonanoronoids A-E (1-5), in conjunction with three previously reported compounds, were isolated from the EtOAc extract of the twigs and leaves of Toona ciliata var. yunnanensis. Their structures were elucidated through comprehensive spectroscopic and X-ray crystallographic analysis. The cytotoxic activities of new compounds against five human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) were screened, Compounds 4 and 5 exerted inhibition toward two tumor cell lines (HL-60, SW-480) with IC50 values between 1.7 and 5.9 µM.

15.
Langmuir ; 40(16): 8352-8364, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38587627

RESUMO

A high yield of environmentally friendly N,S-codoped (N,S-CDs) and N-doping carbon points (N-CDs) carbon dots was achieved through a biochemical oxidation reaction at room temperature in this study. Acetaldehyde, sodium hydroxide, benzotriazole (BTA), and 2-mercaptobenzimidazole (MB) with a similar structure were used as raw materials. The microstructure and properties of the corrosion inhibitor for Q235 steel were evaluated by various experiments. The results demonstrated enhanced corrosion inhibition rates of the N,S-CDs compared to the N-CDs using electrochemical tests (93.83% vs 77.65%) and weight loss experiments (96.35% vs 91.65%) at 50 mg/L, respectively, compared to the blank material, indicating that N,S codoping can significantly improve the corrosion inhibition effect of carbon dots. The significant improvements were attributed to the formation of dense adsorption films and the hydrophobic properties of N and S-CDs nanoparticles on the steel surface, leading to an effective barrier against corrosion. The findings from this study provide important experimental data for potential industrial applications and hold important practical value in the field of pickling corrosion inhibitors.

16.
J Cell Physiol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634445

RESUMO

Krüppel-like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22α expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE-/- mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22α promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet-derived growth factor BB-induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p-AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.

17.
Front Oncol ; 14: 1359807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500663

RESUMO

The use of liquid biopsy in cancer research has grown exponentially, offering potential for early detection, treatment stratification, and monitoring residual disease and recurrence. Exosomes, released by cancer cells, contain tumor-derived materials and are stable in biofluids, making them valuable biomarkers for clinical evaluation. Bibliometric research on osteosarcoma (OS) and exosome-derived diagnostic biomarkers is scarce. Therefore, we aimed to conduct a bibliometric evaluation of studies on OS and exosome-derived biomarkers. Using the Web of Science Core Collection database, Microsoft Excel, the R "Bibliometrix" package, CiteSpace, and VOSviewer software, quantitative analyses of the country, author, annual publications, journals, institutions, and keywords of studies on exosome-derived biomarkers for OS from 1995 to 2023 were performed. High-quality records (average citation rate ≥ 10/year) were filtered. The corresponding authors were mainly from China, the USA, Australia, and Canada. The University of Kansas Medical Center, National Cancer Center, Japan, and University of Kansas were major institutions, with limited cooperation reported by the University of Kansas Medical Center. Keyword analysis revealed a shift from cancer progression to mesenchymal stem cells, exosome expression, biogenesis, and prognostic biomarkers. Qualitative analysis highlighted exosome cargo, including miRNAs, circRNAs, lncRNAs, and proteins, as potential diagnostic OS biomarkers. This research emphasizes the rapid enhancement of exosomes as a diagnostic frontier, offering guidance for the clinical application of exosome-based liquid biopsy in OS, contributing to the evolving landscape of cancer diagnosis.

18.
Bone Res ; 12(1): 17, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472175

RESUMO

While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreERT2; Hif1afl/fl) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreERT2; Hif1afl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.


Assuntos
Ossificação Heterotópica , Osteogênese , Animais , Camundongos , Colágeno/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/genética , Hipóxia/metabolismo , Ossificação Heterotópica/metabolismo , Fatores de Transcrição/metabolismo
19.
Apoptosis ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459420

RESUMO

Hepatocellular carcinoma (HCC) is highly metastatic and invasive. CircRNA participates in gene regulation of multiple tumor metastases, but little is known whether it is a bystander or an actual player in HCC metastasis. We aim to explore the molecular mechanisms of novel circRNAs in HCC metastasis. RT-qPCR was used to detect the expression of 13 circRNAs derived by the ERBB3 gene. The function of circ_0098823 and DNM1L in HCC cells were estimated by CCK-8, transwell assays, flow cytometry, electron microscope, and in vivo experiments. RNA binding protein of circ_0098823 was confirmed by RNA pull-down, mass spectrometry, and RNA immunoprecipitation. The expression of DNM1L after IGF2BP3 knockdown was detected by RT-qPCR and western blot. Circ_0098823 was significantly up-regulated both in HCC tissues and HGF induced cell lines. Circ_0098823 overexpression significantly enhanced proliferation, migration, and invasion but decreased apoptosis of HCC cells, particularly promoted mitochondrial fission. Compared with the control group, the tumors in the circ_0098823 knockdown mice were significantly smaller and lighter. Circ_0098823 silencing suppressed DNM1L expression, a key molecule for fission, which enhanced proliferation, migration and invasion, and inhibited apoptosis of HCC cell. IGF2BP3 was a binding protein of circ_0098823. The expression and mRNA stability of DNM1L were down-regulated by IGF2BP3 knockdown. IGF2BP3 knockdown significantly alleviated the excessive migration, invasion and apoptosis of HCC cells caused by circ_0098823 overexpression. This study uncovered a novel circ_0098823 with tumor-promoting effect, and the mechanism by which circ_0098823 participates in HCC progression through IGF2BP3-guided DNM1L. Our study broadens molecular understanding of HCC progression.

20.
Langenbecks Arch Surg ; 409(1): 106, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556526

RESUMO

PURPOSE: Laparoscopic isolated caudate lobectomy is still a challenging operation for surgeons. The access route of the operation plays a vital role during laparoscopic caudate lobectomy. There are few references regarding this technique. Here, we introduce a preferred inferior vena cava (IVC) approach in laparoscopic caudate lobectomy. METHODS: Twenty-one consecutive patients with caudate hepatic tumours between June 2016 and December 2021 were included in this study. All of them received laparoscopic caudate lobectomy involving an IVC priority approach. The IVC priority approach refers to prioritizing the dissection of the IVC from the liver parenchyma before proceeding with the conventional left or right approach. It emphasizes the importance of the IVC dissection during process. Clinical data, intraoperative parameters and postoperative results were evaluated. Sixteen patients were performed pure IVC priority approach, while 5 patients underwent a combined approach. We subsequently compared the intraoperative and postoperative between the two groups. RESULTS: All 21 patients were treated with laparoscopic technology. The operative time was 190.95 ± 92.65 min. The average estimated blood loss was 251.43 ± 247.45 ml, and four patients needed blood transfusions during the perioperative period. The average duration of hospital stay was 8.43 ± 2.64 (range from 6.0 to 16.0) days. Patients who underwent the pure inferior vena cava (IVC) approach required a shorter hepatic pedicle clamping time (26 vs. 55 min, respectively; P < 0.001) and operation time (150 vs. 380 min, respectively; P = 0.002) than those who underwent the combined approach. Hospitalization (7.0 vs. 9.0 days, respectively; P = 0.006) was shorter in the pure IVC group than in the combined group. CONCLUSIONS: Laparoscopic caudate lobectomy with an IVC priority approach is safe and feasible for patients with caudate hepatic tumours.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Humanos , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Hepatectomia/métodos , Laparoscopia/métodos
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