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INTRODUCTION: Pulmonary regurgitation (PR) remains a common sequela in patients following surgically corrected TOF, and may lead to progressive right ventricle dilatation and dysfunction. The conventional approach of redo-sternotomy for pulmonary valve replacement (PVR) is associated with increased operative time as well as risks of bleeding and injury to the heart and great vessels. Thus, left anterior mini-thoracotomy has become an alternative approach in eliminating the risks of redo-sternotomy in these patients. This series aimed to determine the outcomes of minimally invasive pulmonary valve replacement after surgical TOF correction. METHODS: A retrospective analysis was conducted on 24 patients with severe PR post-surgical TOF correction who underwent left anterior mini-thoracotomy PVR in Penang General Hospital from January 2021 to January 2023. RESULTS: The median age was 23.5 years (I.Q.range 17.6-36.3), with a male:female ratio of 1:4. Majority of patients had mild to moderate symptoms prior to surgery and 19 patients (79.1%) were on regular diuretics medication. All patients had severe free-flow PR with evidence of right ventricular dilatation and dysfunction. Magnetic Resonance Imaging and computed tomography of pulmonary artery were performed prior to surgery. Minimally invasive PVR was performed on all patients via left upper anterior mini-thoracotomy and femoral-femoral bypass without cardioplegic arrest. The operative time and cardiopulmonary bypass time were 208 (I.Q.range 172-324) and 98.6 minutes(I.Q.range 87.4-152.4) respectively. The time to wean off inotropes postoperatively was 6.2 hours (I.Q.range1.4-14.8), and no postoperative arrhythmia and chest re-exploration were reported. Most patients stayed in Intensive Care Unit (ICU) for 10.8 hours (I.Q.range 8.4-36.5), and the total hospital stay was 4.2 days (I.Q.range 3.4-7.6). 2 patients (11.1%) required blood transfusion postoperative. There was no paravalvular leak and no mortality during the follow-up period of up to 28 months. CONCLUSION: Minimally invasive PVR after surgical correction of TOF is a safe alternative to the conventional redo-sternotomy approach in patients with favorable anatomy. This approach is able to reduce the risks associated with redo-sternotomy, particularly bleeding and injury to mediastinal structures, with the additional benefit of expedited recovery and hospital discharge. Our series has shown a safe and efficient approach in these patients with favorable outcomes.
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Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Pulmonar , Tetralogia de Fallot , Toracotomia , Humanos , Masculino , Feminino , Tetralogia de Fallot/cirurgia , Estudos Retrospectivos , Adulto , Toracotomia/métodos , Adolescente , Implante de Prótese de Valva Cardíaca/métodos , Adulto Jovem , Insuficiência da Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Valva Pulmonar/cirurgia , Resultado do TratamentoRESUMO
The aim of the present study was to explore the functional mechanism of NF-Kappa B-interacting Long non-protein coding RNA (NKILA) in breast malignant phyllodes tumors (BMPTs). The expression and functional role of NKILA were investigated by performing qRTâPCR, Transwell assays, and CCKâ8 assays in primary BMPT cells. A KaplanâMeier curve was used to assess overall survival (OS) and local recurrence-free survival (LRFS). The location and expression levels of NKILA and P65 were determined by fluorescence in situ hybridization (FISH) and immunofluorescence (IF), respectively. NKILA was downregulated in patients with BMPT, especially in patients with local recurrence. NKILA had an antitumor effect and promoted the chemosensitivity of cells to cisplatin by blocking P65 phosphorylation and nuclear translocation. In conclusion, NKILA may be a potential therapeutic target for BMPT, especially for BMPT patients with local recurrence.
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Objective: This study aimed to analyse the impact of enterostomal therapist-led visual health education combined with peer education on the postoperative self-nursing ability, quality of life and peristomial complications in patients with a permanent colostomy. Methods: Patients with a permanent colostomy admitted to Second Hospital of Hebei Medical University between March 2021 and March 2023 were selected and divided into the study group (60 patients) and the control group (60 patients). Enterostomal therapist-led visual health education combined with peer education was adopted in the study group, and regular education was adopted in the control group. The clinical effects between the two groups were compared. Results: Repeated measurement analysis of variance showed that the two educational methods had different effects on the quality of life (Ftreatment = 342.734, p < 0.001), self-nursing ability (Ftreatment = 256.321, p < 0.001), adaptability (Ftreatment = 321.734, p < 0.001) of patients with a permanent colostomy. After the 3-month intervention, the differences in all aspects of the quality of life, self-nursing ability and adaptability between the two groups were statistically significant, and the score of the study group was higher than that of the control group (p < 0.05). Compared with the control group, the study group had a lower incidence of the five complications (p < 0.05) and higher nursing satisfaction (Z = -2.968, p < 0.05). Conclusion: Enterostomal therapist-led visual health education combined with peer education can improve the quality of life of patients with a permanent colostomy, improve their positive mood, reduce their negative mood, improve their adaptability to the stoma, reduce complications and improve their daily living conditions. In the future, the clinical application of visual health education and peer education in patients with permanent colostomy should be increased.
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As the incidence of endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) has been increasing, and has shown young trend. It is crucial to study the fertility-preserving treatment of endometrial lesions and fertility-promoting protocols. Age, obesity, and irregular ovulation are not only high-risk factors for endometrial lesions but also key factors affecting female fertility. Assisted reproductive technology (ART) can significantly improve pregnancy outcomes in patients with AEH and EC after conservative treatment. Based on the existing studies, this article reviews the progress of research on pregnancy outcomes of ART and its influencing factors in such patients. It helps physicians in providing optimal fertility guidance.
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Tratamento Conservador , Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Técnicas de Reprodução Assistida , Humanos , Feminino , Neoplasias do Endométrio/terapia , Neoplasias do Endométrio/patologia , Hiperplasia Endometrial/terapia , Hiperplasia Endometrial/patologia , Gravidez , Tratamento Conservador/métodos , Preservação da Fertilidade/métodos , Resultado da Gravidez , Infertilidade Feminina/terapia , Infertilidade Feminina/etiologiaRESUMO
OBJECTIVES: To evaluate the neutralizing antibody (NAb) levels against the SARS-CoV-2 Omicron variants BF.7, BQ.1, BQ.1.1, XBB.1, and XBB.1.5 after vaccination and natural infection. METHODS: The NAbs against the different viral strains of 490 individuals with SARS-CoV-2 and 187 without SARS-CoV-2 in the Beijing COVID-19 outbreak during December 2022 to January 2023 were analyzed. RESULTS: In uninfected individuals, limited levels of NAbs were produced against the prototype and variant strains after two doses vaccine but significantly increased after three or four doses of the vaccine. The infected individuals had high NAbs levels against the BF.7, BQ.1, and BQ.1.1 variants and moderate NAbs levels against the XBB.1 and XBB.1.5 variants. The highest NAbs levels were observed after two inoculation doses. The third and fourth doses vaccine did not result in a significant increase the NAbs levels. After the last dose of vaccination, the NAbs levels peaked at 12 months for the prototype and BF.7 and between 6 to 12 months for the BQ.1, BQ.1.1, XBB.1, and XBB.1.5 variants. CONCLUSIONS: The immune response decreases as the virus mutates. If booster vaccination is considered necessary, it is suggested for at least 6 months after infection.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinação , Humanos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Masculino , Feminino , Adulto , Vacinas contra COVID-19/imunologia , Pessoa de Meia-Idade , Idoso , Adulto Jovem , AdolescenteRESUMO
Purifying C2H6/C3H8 from a ternary natural gas mixture through adsorption separation is an important but challenging process in the petrochemical industry. To address this challenge, the industry is exploring effective strategies for designing high-performance adsorbents. In this study, we present two metal-organic frameworks (MOFs), DMOF-TF and DMOF-(CF3)2, which have fluorinated pores obtained by substituting linker ligands in the host material. This pore engineering strategy not only provides suitable pore confinement but also enhances the adsorption capacities for C2H6/C3H8 by providing additional binding sites. Theoretical calculations and transient breakthrough experiments show that the introduction of F atoms not only improves the efficiency of natural gas separation but also provides multiple adsorption sites for C2H6/C3H8-framework interactions.
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PURPOSE: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) in combination with tyrosinkinase inhibitors (TKI) and PD-1 inhibitors, versus TACE monotherapy for the treatment of ruptured hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study included 104 patients with ruptured HCC receiving either combination therapy or TACE monotherapy at two centers between June 2015 and June 2022. Propensity score matching (PSM) analysis was used at a 1:2 ratio to reduce bias between the two groups. The primary outcome measures were overall survival (OS) and progression-free survival (PFS), and the secondary outcome measures were the occurrence of adverse events (AEs, Common Terminology Criteria for AEs, version 5.0.) and the peritoneal metastasis rate. RESULTS: A total of 69 patients were enrolled after PSM, including 23 patients in the combination group and 46 patients in the monotherapy group. The combination group exhibited a significantly longer median OS (553 days, 95% confidence interval [CI] 222.6-883.9) compared to the monotherapy group (105 days, 95% CI 81.2-128.7; P < 0.001). Similarly, the combination group showed a better median PFS (356 days, 95% CI 299.5-412.4) compared to the monotherapy group (97 days, 95% CI 75.9-118.1; P < 0.001). Moreover, there was no significant difference in the peritoneal metastasis rate (combination group: 8.6% vs. monotherapy group: 26.1%, P = 0.119). Grade 3 AEs occurred at a rate of 21.7% and 13% in combination and monotherapy groups, respectively. No Grade 4/5 AEs were observed in either group. CONCLUSIONS: Our study demonstrated that the combination of TACE with TKI and PD-1 inhibitors significantly enhances OS and PFS compared to TACE monotherapy in ruptured HCC patients. Furthermore, this combined approach exhibited an acceptable safety profile.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Neoplasias Peritoneais , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Quimioembolização Terapêutica/efeitos adversos , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/etiologia , Estudos RetrospectivosRESUMO
Microfluidic organs and organoids-on-a-chip models of human gastrointestinal systems have been established to recreate adequate microenvironments to study physiology and pathophysiology. In the effort to find more emulating systems and less costly models for drugs screening or fundamental studies, gastrointestinal system organoids-on-a-chip have arisen as promising pre-clinicalin vitromodel. This progress has been built on the latest developments of several technologies such as bioprinting, microfluidics, and organoid research. In this review, we will focus on healthy and disease models of: human microbiome-on-a-chip and its rising correlation with gastro pathophysiology; stomach-on-a-chip; liver-on-a-chip; pancreas-on-a-chip; inflammation models, small intestine, colon and colorectal cancer organoids-on-a-chip and multi-organoids-on-a-chip. The current developments related to the design, ability to hold one or more 'organs' and its challenges, microfluidic features, cell sources and whether they are used to test drugs are overviewed herein. Importantly, their contribution in terms of drug development and eminent clinical translation in precision medicine field, Food and Drug Administration approved models, and the impact of organoid-on-chip technology in terms of pharmaceutical research and development costs are also discussed by the authors.
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Trato Gastrointestinal , Sistemas Microfisiológicos , Estados Unidos , Humanos , Estômago , Fígado , OrganoidesRESUMO
Introduction: This study was undertaken to examine the expression of miR-575 in thyroid cancer tissues and to explore its therapeutic potential. Material and methods: Expression analysis was carried out by qRT-PCR. The MTT assay was used for cell viability. DAPI and annexin V/PI assays were used to detect apoptosis. Wound healing and Transwell assays were used for cell migration and invasion respectively. Western blot analysis was used to determine the expression of proteins. Results: The results showed significant downregulation of miR-575 in thyroid cancer tissues and cell lines. The role of miR-575 was deciphered by overexpression of miR-575 in MDA-T32 and MDA-T68 thyroid cancer cells. The results showed that overexpression of miR-575 caused significant inhibition of the proliferation of the MDA-T32 and MDA-T68 cells via induction of apoptotic cell death. The expression of Bax was also enhanced while that of Bax was decreased upon miR-575 overexpression in MDA-T32 and MDA-T68 cells. Additionally, miR-575 overexpression inhibited the migration and invasion of the MDA-T32 and MDA-T68 thyroid cancer cells. Bioinformatic approaches and the dual luciferase assay indicated Derlin 1 (DERL1) to be the potential target of miR-575 in thyroid cancer. DERL1 was significantly upregulated in thyroid cancer tissues and cell lines and overexpression of miR-575 caused suppression of DERL1 in MDA-T68 cells. Silencing of DERL1 inhibited the proliferation of the MDA-T68 cells while overexpression of DERL1 could abolish the effects of miR-575 overexpression on the proliferation of MDA-T68 thyroid cancer cells. Conclusions: miR-575 may be used as a therapeutic target for thyroid cancer treatment.
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BACKGROUND: Therapy for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) is still controversial. This study was performed to evaluate the efficacy and safety of the combination therapy comprising transarterial chemoembolization (TACE), lenvatinib (L), programmed death-1 inhibitor (P), and iodine-125 seed (I125) brachytherapy relative to TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy and TACE plus lenvatinib therapy. METHODS: The data of HCC patients with PVTT from July 2017 to August 2022 were assessed in this single-center retrospective study. Primary study outcomes were progression-free survival (PFS) and overall survival (OS), while the secondary outcomes were disease control rate (DCR), objective response rate (ORR), and treatment-related adverse events. RESULTS: We enrolled 150 patients totally, including 50 patients treated with TACE plus lenvatinib therapy (TACE+L group), 45 patients treated with TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy (TACE+L+P group), and 55 patients treated with the combination therapy of TACE along with I125 brachytherapy, lenvatinib, and programmed death-1 inhibitor therapy (TACE+L+P+I125 group). The median OS in the TACE+L+P+I125 group (21.0; 95% confidence interval [CI]: 18.4â¼23.5 months) was significantly longer than that in the TACE+L group (10; 95% CI: 7.8â¼12.1months) (pâ¯=â¯0.006), while it was insignificantly longer than that in the TACE+L+P group (14.0; 95% CI: 10.7â¼17.2months) (pâ¯=â¯0.058). The median PFS in the TACE+L+P+I125 group (13.0; 95% CI: 10.2â¼15.7 months) was significantly longer than that in the TACE+L group (5.0; 95% CI: 4.2â¼5.7 months) (pâ¯=â¯0.014) and the TACE+L+P group (9.0; 95% CI: 6.7â¼11.2 months) (pâ¯=â¯0.048). Statistically significant differences between groups were found in DCR (pâ¯=â¯0.015). There were no significant between-group differences in treatment-related adverse events (p > 0.05). CONCLUSIONS: A combination therapy of TACE, lenvatinib, programmed death-1 inhibitor, and I125 seed brachytherapy significantly improve OS, PFS, and DCR and show better survival prognosis for HCC patients accompanied by PVTT.
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Braquiterapia , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Radioisótopos do Iodo , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Trombose , Humanos , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Braquiterapia/métodos , Veia Porta , Estudos Retrospectivos , SementesRESUMO
A total of nine new phenolic amides (1-9), including four pairs of enantiomeric mixtures (3-5 and 8), along with ten known analogues (10-19) were identified from the fruits of Lycium barbarum using bioassay-guided chromatographic fractionation. Their structures were elucidated by comprehensive spectroscopic and spectrometric analyses, chiral HPLC analyses, and quantum NMR, and electronic circular dichroism calculations. Compounds 5-7 are the first example of feruloyl tyramine dimers fused through a cyclobutane ring. The activity results indicated that compounds 1, 11, and 13-17 exhibited remarkable inhibition against α-glucosidase with IC50 of 1.11-33.53 µM, 5-150 times stronger than acarbose (IC50 = 169.78 µM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-γ), with EC50 values of 10.09-44.26 µM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC50 value of 47.13 µM. Furthermore, the banding manner of compounds 14 and 17 with the active site of α-glucosidase, DPPIV, and PPAR-γ was explored by employing molecular docking analysis.
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Lycium , alfa-Glucosidases , alfa-Glucosidases/análise , Frutas/química , Lycium/química , Receptores Ativados por Proliferador de Peroxissomo , Agonistas PPAR-gama , Amidas , Simulação de Acoplamento Molecular , Fenóis/análise , Espectroscopia de Ressonância Magnética , Dipeptidil Peptidases e Tripeptidil Peptidases/análise , Estrutura Molecular , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/químicaRESUMO
The intranasal spray COVID-19 vaccine was made available for the first time in China, it is necessary to understand receivers' satisfaction and experience toward the vaccine to help optimize vaccination service. A self-administered multicenter cross-sectional questionnaire survey was conducted in Beijing, China, in December 2022. The vaccination experience was evaluated through three dimensions: immediate tolerance, smooth progress, and time-saving. Vaccine acceptability was measured by receivers' preference for the intranasal spray over intramuscular injection after vaccination and their recommendation willingness. Stepwise multinomial and binary logistic regression models were applied to investigate factors associated with vaccine acceptability. Among 10,452 participants included in the analysis, 92.6% felt no discomfort during the inoculation, 99.8% thought the vaccination process went well, and 89.4% deemed it a time-saving option. For vaccine acceptability, 5566 (53.3%) participants were willing to recommend the vaccine to others, 534 (5.1%) refused, and 4352 (41.6%) had not decided yet; 6142 (58.8%) participants preferred the intranasal spray, 873 (8.4%) preferred the intramuscular injection, and 3437 (32.9%) had no preferences. The most concerned aspects of the intranasal spray vaccine were vaccine effectiveness and safety. Receivers who perceived higher vaccine effectiveness or safety were more likely to recommend it to others (OR, 95%CI: 4.41, 3.24-6.00; 6.11, 4.52-8.27) or prefer it over intramuscular injection after vaccination (OR, 95%CI: 5.94, 4.62-7.65; 8.50, 6.70-10.78). Receivers showed good acceptability and experience toward the intranasal spray COVID-19 vaccine. Vaccine effectiveness and safety were the most concerned aspects, and corresponding publicity and education efforts may help improve vaccine acceptability.
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COVID-19 , Vacinas contra Influenza , Orthomyxoviridae , Humanos , Vacinas contra COVID-19 , Estudos Transversais , Pequim , COVID-19/prevenção & controle , China , VacinaçãoRESUMO
The combination of chirality and phase-transition materials has broad application prospects. Therefore, based on the quasi-spherical theory and the thought strategy of introducing chirality, we have successfully synthesized a pair of chiral enantiomeric ligands (R/S)-triethyl-(2-hydroxypropyl)ammonium iodide, which can be combined with a tin hexachloride anion to obtain a pair of new organic-inorganic hybrid enantiomeric high-temperature plastic phase-transition materials: (R/S)-[CH3 CH(OH)CH2 N(CH2 CH3 )3 ]2 SnCl6 (1-R/1-S), which have a high temperature phase transition of Tc =384â K, crystallize in the P21 chiral space group at room temperature, and have obvious CD signals. In addition, compounds 1-R and 1-S have a good low-loss dielectric switch and broadband gap. This work is conducive to the research into chiral high-temperature reversible plastic phase-transition materials, and promotes the development of multi-functional phase-transition materials.
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Background: The subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib. Methods: In this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. Results: We enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p < 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029). Conclusions: A combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.
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Three new monomeric (1-3) and two newdimeric guaianolides (4 and 5), along with three known analogues (6-8) were isolated from the aerial part of Achillea alpina L. Compounds 1-3 were three novel 1,10-seco-guaianolides, while 4 and 5 were two novel 1,10-seco-guaianolides involved heterodimeric [4 + 2] adducts. The new structures were elucidated by analysis of spectroscopic data and quantum chemical calculations. All isolates were evaluated for their hypoglycemic activity with a glucose consumption model in palmitic acid (PA)-induced HepG2-insulin resistance (IR) cells, and compound 1 showed the most promising activity. A mechanistic study revealed that compound 1 appeared to mediate hypoglycemic activity via inhibition of the ROS/TXNIP/NLRP3/caspase-1 pathway.
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Achillea , Sesquiterpenos , Achillea/química , Estrutura Molecular , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Sesquiterpenos/farmacologia , Sesquiterpenos/químicaRESUMO
Basic pre-clinical research based on 2D cultures have been very valuable in colorectal cancer (CRC) research but still have failed to improve patient prognostic outcomes. This is because they simply do not replicate what happensin vivo, i.e.2D cultured cells system cannot replicate the diffusion constraints usually found in the body. Importantly, they also do not mimic the dimensionality of the human body and of a CRC tumour (3D). Moreover, 2D cultures lack the cellular heterogeneity and the tumour microenvironment (TME) such as stromal components, blood vessels, fibroblasts, and cells of the immune system. Cells behave differently whether in 2D and 3D, in particular their different genetic and protein expression panels are very different and therefore we cannot fully rely on drug tests done in 2D. A growing field of research based on microphysiological systems involving organoids/spheroids or patient-derived tumour cells has become a solid base for a better understanding of the TME and as a result is a step towards personalized medicine. Furthermore, microfluidic approaches have also started to open possibilities of research, with tumour-on-chips and body-on-chips being used in order to decipher complex inter-organ signalling and the prevalence of metastasis, as well as CRC early-diagnosis through liquid biopsies. Herein, we focus on the state-of-the-art of CRC research with emphasis on 3D microfluidicin vitrocultures-organoids, spheroids-drug resistance, circulating tumour cells and microbiome-on-a-chip technology.
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Neoplasias Colorretais , Sistemas Microfisiológicos , Humanos , Esferoides Celulares , Organoides , Fibroblastos , Microambiente TumoralRESUMO
Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and mßCD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.
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PURPOSE: The aim of this study was to explore the effect and mechanism of pirfenidone (PFD) combined with 2-methoxyestradiol (2-ME2) perfusion through portal vein on hepatic artery hypoxia-induced hepatic fibrosis. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 5 groups (n â= â3/group): control group, hepatic artery ligation (HAL) group, HAL â+ âPFD (portal vein perfusion of PFD) group, HAL+2-ME2 (portal vein perfusion of 2-ME2) group and HAL â+ âPFD+2-ME2 group depending on whether they received HAL and/or portal vein perfusion (PFD and/or 2-ME2). Livers were harvested for pathology, western blotting (WB), and quantitative real-time PCR (qRT-PCR). RESULTS: Sirius red staining showed that portal vein perfusion of drugs resulted in degradation of liver fibrosis. Immunohistochemistry showed decreased hypoxia-inducible factor-1 α (HIF-1α) and α-smooth muscle actin (α-SMA) after portal intravenous drugs infusion compared with HAL group (P â< â0.05). WB analysis showed increased Smad7 in HAL â+ âPFD group compared with HAL group (P â< â0.05). qRT-PCR analysis showed decreased matrix metallo-proteinase 2 (MMP2), transforming growth factor ß1 (TGF-ß1), monocyte chemoattractant protein-1 (MCP-1), and Collagen I mRNA in HAL â+ âPFD group except for tissue inhibitor of metalloproteinase-1 (TIMP-1) compared with HAL group (P â< â0.05). Compared with HAL â+ âPFD group, the addition of 2-ME2 did not lead to better results in qRT-PCR analysis. CONCLUSIONS: The portal vein perfusion of PFD significantly reduced the hepatic artery hypoxia-induced fibrosis degree in treated rats by down-regulating the expression of HIF-1α, α-SMA, MMP2, TGF-ß1, MCP-1, and Collagen I, as well as up-regulating the TIMP-1 expression and Smad7 protein level. Combined 2-ME2 infusion was not better than PFD alone.
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Artéria Hepática , Veia Porta , Ratos , Animais , Artéria Hepática/metabolismo , Veia Porta/metabolismo , Fator de Crescimento Transformador beta1/efeitos adversos , Fator de Crescimento Transformador beta1/metabolismo , Metaloproteinase 2 da Matriz , Inibidor Tecidual de Metaloproteinase-1/genética , 2-Metoxiestradiol/farmacologia , 2-Metoxiestradiol/uso terapêutico , Ratos Sprague-Dawley , Cirrose Hepática/tratamento farmacológico , Fibrose , Perfusão , Hipóxia , ColágenoRESUMO
One new 6a,11a-dehydropterocarpan derivative, 6-O-methyl-anhydrotuberosin (1), one new 6a-hydroxypterocarpan, (6aR,11aR,11bR)-hydroxytuberosone (7), and seven known compounds including two 6a,11a-dehydropterocarpans (2 and 4), two coumestans (3 and 5), one isoflavonoid (6) and two other phenolic compounds (8 and 9) were isolated from the roots of Pueraria lobata. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods (1 D and 2DNMR, HRESIMS). Compounds 1, 2, 4-5 showed potent LSD1 inhibitory activities with IC50 values ranging from 1.73 to 4.99 µM. Furthermore, compound 2 showed potent cytotoxicity against gastric cancer cell lines MGC-803 and BGC-823, and lung cancer cell lines H1299 and H460.