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1.
Adv Sci (Weinh) ; : e2403262, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38973296

RESUMEN

Despite docetaxel combined with cisplatin and 5-fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48-linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)-like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG-like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7-USP10-G3BP1 axis contains potential targets and biomarkers for NPC treatment.

2.
Radiat Oncol ; 19(1): 88, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38978062

RESUMEN

PURPOSE: This study aimed to develop an automated Tomotherapy (TOMO) planning method for cervical cancer treatment, and to validate its feasibility and effectiveness. MATERIALS AND METHODS: The study enrolled 30 cervical cancer patients treated with TOMO at our center. Utilizing scripting and Python environment within the RayStation (RaySearch Labs, Sweden) treatment planning system (TPS), we developed automated planning methods for TOMO and volumetric modulated arc therapy (VMAT) techniques. The clinical manual TOMO (M-TOMO) plans for the 30 patients were re-optimized using automated planning scripts for both TOMO and VMAT, creating automated TOMO (A-TOMO) and automated VMAT (A-VMAT) plans. We compared A-TOMO with M-TOMO and A-VMAT plans. The primary evaluated relevant dosimetric parameters and treatment plan efficiency were assessed using the two-sided Wilcoxon signed-rank test for statistical analysis, with a P-value < 0.05 indicating statistical significance. RESULTS: A-TOMO plans maintained similar target dose uniformity compared to M-TOMO plans, with improvements in target conformity and faster dose drop-off outside the target, and demonstrated significant statistical differences (P+ < 0.01). A-TOMO plans also significantly outperformed M-TOMO plans in reducing V50Gy, V40Gy and Dmean for the bladder and rectum, as well as Dmean for the bowel bag, femoral heads, and kidneys (all P+ < 0.05). Additionally, A-TOMO plans demonstrated better consistency in plan quality. Furthermore, the quality of A-TOMO plans was comparable to or superior than A-VMAT plans. In terms of efficiency, A-TOMO significantly reduced the time required for treatment planning to approximately 20 min. CONCLUSION: We have successfully developed an A-TOMO planning method for cervical cancer. Compared to M-TOMO plans, A-TOMO plans improved target conformity and reduced radiation dose to OARs. Additionally, the quality of A-TOMO plans was on par with or surpasses that of A-VMAT plans. The A-TOMO planning method significantly improved the efficiency of treatment planning.


Asunto(s)
Órganos en Riesgo , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Femenino , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Órganos en Riesgo/efectos de la radiación
3.
Neoplasia ; 56: 101029, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39024777

RESUMEN

OBJECTIVE: Pyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study explored the efficacy and safety of pyrotinib in the treatment of HER2-positive MBC patients in the real world. METHODS: From September 2018 to February 2022, 137 female patients with HER2-positive MBC treated in this center were enrolled in this study. The follow-up period ended on January 12, 2023. The primary endpoint of this study was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), central nervous system (CNS)-PFS, CNS-ORR, CNS-CBR, CNS-DCR, and adverse event (AE) were the secondary endpoints. RESULTS: The ORR, DCR and CBR were 41.98 % (55/131), 87.79 % (115/131) and 44.27 % (58/131) in this cohort, respectively. The median PFS for this cohort was 10.37 months [95 % confidence interval (CI): 9.205-11.535] and the median OS was 37.53 months (not reached). Univariate and multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio (HR): 0.579 (0.371-0.904, p=0.016)] and improved OS [0.410 (0.213-0.790, p=0.008)]. Patients treated with a pyrotinib-based regimen as second-line and third-or-post-line therapy had poorer PFS [second-line: 3.315 (1.832-6.000, p<0.001); third-or-post-line: 3.304 (1.749-6.243, p<0.001)] and OS [second-line: 4.631 (1.033-20.771, p=0.045); third-or-post-line: 5.738 (1.212-27.174, p=0.028)]. There were 38 brain metastases (BM) patients in this study, the CNS-mPFS [14.37 months (7.815-20.925) vs. 7.83 months (7.047-8.613), p=0.375] and mOS [not reached vs. 36.40 months (18.551-54.249), p=0.034] were better in brain radiotherapy (BRT) group than NBRT group. 18.98 % (26/137) of patients experienced grade 3 or higher diarrhea. No AE-related death was reported. CONCLUSION: This study confirms the promising antitumor activity and acceptable safety of real-world pyrotinib-based regimens for the treatment of HER2-positive MBC patients, particularly those who are trastuzumab-sensitive and who are receiving pyrotinib-based regimens as advanced first-line therapy. It has also been demonstrated that these regimens combined with BRT, provide better intracranial responses and long-term survival benefits for these patients with BM.

4.
J Med Virol ; 96(7): e29793, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39023111

RESUMEN

Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with messenger RNA (mRNA) vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT, Moderna), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using liquid chromatography coupled to tandem mass spectrometry. Antibody-dependent-cellular-phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured by flow cytometry. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD was significantly lower in AstraZeneca-vaccinated individuals. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.


Asunto(s)
Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina G , SARS-CoV-2 , Vacunas de Subunidad , Vacunas de ARNm , Humanos , Inmunoglobulina G/sangre , Femenino , Anticuerpos Antivirales/sangre , Masculino , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Adulto , Persona de Mediana Edad , Vacunas contra la COVID-19/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/genética , Vacunas de Subunidad/administración & dosificación , Glicosilación , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Anciano , ARN Mensajero/genética , Adulto Joven , Vacunas de Subunidades Proteicas
5.
Neurol Res ; : 1-11, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39033031

RESUMEN

OBJECTIVE: Previously, we have successfully purified and synthesized viscolin, an agent derived from Viscum coloratum extract, which has shown significant potential in the treatment of stroke. Our study aimed to evaluate the neuroprotective effects of viscolin. METHODS: We first assessed the cytotoxicity of viscolin on primary neuronal cultures and determined its antioxidant and radical scavenging properties. Subsequently, we identified the optimal dose-response of viscolin in protecting against glutamate-induced neurotoxicity. RESULTS: Our results demonstrated that viscolin at a concentration of 10 µM effectively reduced neuronal cell death up to 6 hours after glutamate-induced neurotoxicity. Additionally, we investigated the therapeutic window of opportunity and the potential of viscolin in preventing necrotic and apoptotic damage in cultured neurons exposed to oxygen glucose deprivation-induced neurotoxicity. Our findings showed that viscolin treatment significantly reduced DNA breakage, prevented the release of cytochrome c from mitochondria to cytosol, increased the expression of anti-apoptotic protein Bcl-2, decreased the expression of pro-apoptotic protein Bax, and reduced the number of TUNEL-positive cells. Additionally, our in vivo investigation demonstrated a reduction in brain infarction following middle cerebral artery occlusion. CONCLUSION: Viscolin has potential utility as a therapeutic agent in the treatment of stroke.

6.
Food Chem ; 459: 140451, 2024 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-39029424

RESUMEN

Bisphenols threaten human health and sensitive detection is crucial. The present study aims to develop ternary composites of copper metal-organic framework (Cu-MOF) with AuAg microstructures. The composite structure was formed by a galvanic displacement reaction and confirmed using SEM. A binder-free catalyst was used to study the electrochemical redox reaction of bisphenol A (BPA) and bisphenol S (BPS); an irreversible cyclic voltammetric signal at +0.70 V and + 0.91 V (vs. Ag/AgCl), in the dynamic range of 20 nM to 2.0 mM, and 10 nM to 1.0 mM, with limits of detection of 2.9 nM, and 3.2 nM (S/N = 3) was obtained. Practical analysis was applied to frozen tomatoes, tuna fish, milk powder, PET bottles, raw milk, and urine samples with a recovery rate of 94.00-100.80% (n = 3). Voltammetric results were validated using HPLC detection with high precision. The sensor is a promising alternative platform for measuring BPA in food samples.

7.
Materials (Basel) ; 17(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38998236

RESUMEN

The binder ratio in a commercial lithium-ion battery is very low, but it is one of the key materials affecting the battery's performance. In this paper, polycarbonate-based polymers with liner or chain extension structures are proposed as binders. Then, dry LiFePO4 (LFP) electrodes with these binders are prepared using the solvent-free method. Polycarbonate-based polymers have a high tensile strength and a satisfactory bonding strength, and the rich polar carbonate groups provide highly ionic conductivity as binders. The batteries with poly (propylene carbonate)-plus (PPC-P) as binders were shown to have a long cycle life (350 cycles under 1 C, 89% of capacity retention). The preparation of dry electrodes using polycarbonate-based polymers can avoid the use of solvents and shorten the process of preparing electrodes. It can also greatly reduce the manufacturing cost of batteries and effectively use industrial waste gas dioxide oxidation. Most importantly, a battery material with this kind of polycarbonate polymer as a binder is easily recycled by simply heating after the battery is discarded. This paper provides a new idea for the industrialization and development of a novel binder.

8.
Nanomaterials (Basel) ; 14(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38998725

RESUMEN

Poly(propylene carbonate-co-phthalate) (PPC-P) is an amorphous copolymer of aliphatic polycarbonate and aromatic polyester; it possesses good biodegradability, superior mechanical performances, high thermal properties, and excellent affinity with CO2. Hence, we fabricate PPC-P foams in an autoclave by using subcritical CO2 as a physical blowing agent. Both saturation pressure and foaming temperature affect the foaming behaviors of PPC-P, including CO2 adsorption and desorption performance, foaming ratio, cell size, porosity, cell density, and nucleation density, which are investigated in this research. Moreover, the low-cost PPC-P/nano-CaCO3 and PPC-P/starch composites are prepared and foamed using the same procedure. The obtained PPC-P-based foams show ultra-high expansion ratio and refined microcellular structures simultaneously. Besides, nano-CaCO3 can effectively improve PPC-P's rheological properties and foamability. In addition, the introduction of starch into PPC-P can lead to a large number of open cells. Beyond all doubt, this work can certainly provide both a kind of new biodegradable PPC-P-based foam materials and an economic methodology to make biodegradable plastic foams. These foams are potentially applicable in the packaging, transportation, and food industry.

9.
Nanomaterials (Basel) ; 14(13)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38998763

RESUMEN

Lithium metal has been treated as one of the most promising anode materials for next-generation rechargeable batteries due to its extremely high theoretical capacity. However, its practical application is hindered by inhomogeneous lithium deposition and uncontrolled dendrite growth. In this work, we prepared a three-dimensional nickel foam (NF)-based current collector with a lithiophilic interface layer through facile hydrothermal and coating methods. The lithiophilic Ni3S2 array synthesized via a hydrothermal method has been demonstrated to facilitate the nucleation of Li+. Moreover, it has been observed that the outer coating comprising LPP effectively enhances the inward diffusion of Li+. Additionally, this interface layer can serve as an isolating barrier between the electrodes and the electrolyte. The prepared LPP-Ni3S2@Ni shows significant reversibility both in symmetric cells (1200 h, 1 mA cm-2) and half-cells (CE: 99.60%, 500 cycles, 1 mA cm-2) with low interfacial resistance (35 Ω). Full cells with LiFePO4 as a cathode also exhibit promising electrochemical performance with over 76.78% capacity retention over 200 cycles at 1 C.

10.
Inorg Chem ; 63(28): 12803-12809, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38957131

RESUMEN

A high-nuclear Co-added polyoxometalate (CoAP) was synthesized via a hydrothermal reaction: H14.5K9Na7.5-{[Co8(µ2-OH)(µ3-OH)2(H2O)2(Co(H2O)GeW6O26)(B-α-GeW9O34)2][BO(OH)2][Co12(µ2-OH)(µ3-OH)5(H2O)3(Co(H2O)GeW6O26)(GeW6O26)(B-α-GeW9O34)]}·46H2O (1). The polyoxoanion of 1 contains a large Co20 cluster gathered by lacunary GeW6O26 and GeW9O34 subunits. 1 represents a one-dimensional (1D) chain formed by adjacent polyoxoanions coupling through a CoO6 double bridge, showing the first example of a high-nuclear CoAP-based inorganic chain. 1 served as an efficient electrocatalyst in oxygen evolution reactions (OERs).

11.
Plant J ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995679

RESUMEN

Bacterial leaf streak (BLS), caused by Xanthomonas oryzae pv. oryzicola (Xoc), is a major bacterial disease in rice. Transcription activator-like effectors (TALEs) from Xanthomonas can induce host susceptibility (S) genes and facilitate infection. However, knowledge of the function of Xoc TALEs in promoting bacterial virulence is limited. In this study, we demonstrated the importance of Tal10a for the full virulence of Xoc. Through computational prediction and gene expression analysis, we identified the hexokinase gene OsHXK5 as a host target of Tal10a. Tal10a directly binds to the gene promoter region and activates the expression of OsHXK5. CRISPR/Cas9-mediated gene editing in the effector binding element (EBE) of OsHXK5 significantly increases rice resistance to Xoc, while OsHXK5 overexpression enhances the susceptibility of rice plants and impairs rice defense responses. Moreover, simultaneous editing of the promoters of OsSULTR3;6 and OsHXK5 confers robust resistance to Xoc in rice. Taken together, our findings highlight the role of Tal10a in targeting OsHXK5 to promote infection and suggest that OsHXK5 represents a potential target for engineering rice resistance to Xoc.

13.
J Control Release ; 371: 530-554, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38857787

RESUMEN

Wound management remains a great challenge for clinicians due to the complex physiological process of wound healing. Porous silicon (PSi) with controlled pore morphology, abundant surface chemistry, unique photonic properties, good biocompatibility, easy biodegradation and potential bioactivity represent an exciting class of materials for various biomedical applications. In this review, we focus on the recent progress of PSi in the design of advanced sensing and delivery systems for wound management applications. Firstly, we comprehensively introduce the common type, normal healing process, delaying factors and therapeutic drugs of wound healing. Subsequently, the typical fabrication, functionalization and key characteristics of PSi have been summarized because they provide the basis for further use as biosensing and delivery materials in wound management. Depending on these properties, the rise of PSi materials is evidenced by the examples in literature in recent years, which has emphasized the robust potential of PSi for wound monitoring, treatment and theranostics. Finally, challenges and opportunities for the future development of PSi-based sensors and delivery systems for wound management applications are proposed and summarized. We hope that this review will help readers to better understand current achievements and future prospects on PSi-based sensing and delivery systems for advanced wound management.


Asunto(s)
Sistemas de Liberación de Medicamentos , Silicio , Cicatrización de Heridas , Silicio/química , Humanos , Porosidad , Cicatrización de Heridas/efectos de los fármacos , Animales , Sistemas de Liberación de Medicamentos/métodos , Técnicas Biosensibles/métodos
14.
PLoS Negl Trop Dis ; 18(6): e0012268, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38870242

RESUMEN

Dengue virus (DENV) causes approximately 390 million dengue infections worldwide every year. There were 22,777 reported DENV infections in Tainan, Taiwan in 2015. In this study, we sequenced the C-prM-E genes from 45 DENV 2015 strains, and phylogenetic analysis based on C-prM-E genes revealed that all strains were classified as DENV serotype 2 Cosmopolitan genotype. Sequence analysis comparing different DENV-2 genotypes and Cosmopolitan DENV-2 sequences prior to 2015 showed a clade replacement event in the DENV-2 Cosmopolitan genotype. Additionally, a major substitution C-A314G (K73R) was found in the capsid region which may have contributed to the clade replacement event. Reverse genetics virus rgC-A314G (K73R) showed slower replication in BHK-21 and C6/36 cells compared to wildtype virus, as well as a decrease in NS1 production in BHK-21-infected cells. After a series of passaging, the C-A314G (K73R) mutation reverted to wildtype and was thus considered to be unstable. Next generation sequencing (NGS) of three sera collected from a single DENV2-infected patient at 1-, 2-, and 5-days post-admission was employed to examine the genetic diversity over-time and mutations that may work in conjunction with C-A314G (K73R). Results showed that the number of haplotypes decreased with time in the DENV-infected patient. On the fifth day after admission, two new haplotypes emerged, and a single non-synonymous NS4A-L115I mutation was identified. Therefore, we have identified a persistent mutation C-A314G (K73R) in all of the DENV-2 isolates, and during the course of an infection, a single new non-synonymous mutation in the NS4A region appears in the virus population within a single host. The C-A314G (K73R) thus may have played a role in the DENV-2 2015 outbreak while the NS4A-L115I may be advantageous during DENV infection within the host.


Asunto(s)
Virus del Dengue , Dengue , Brotes de Enfermedades , Genotipo , Epidemiología Molecular , Filogenia , Virus del Dengue/genética , Virus del Dengue/clasificación , Dengue/epidemiología , Dengue/virología , Taiwán/epidemiología , Humanos , Mutación , Análisis Mutacional de ADN , Animales , Línea Celular , Variación Genética
16.
Drug Resist Updat ; 76: 101111, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38908233

RESUMEN

Gemcitabine (GEM) based induction chemotherapy is a standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, approximately 15 % of patients are still resistant to GEM-containing chemotherapy, which leads to treatment failure. Nevertheless, the underlying mechanisms of GEM resistance remain poorly understood. Herein, based on a microarray analysis, we identified 221 dysregulated lncRNAs, of which, DYNLRB2-AS1 was one of the most upregulated lncRNAs in GEM-resistance NPC cell lines. DYNLRB2-AS1 was shown to function as contain an oncogenic lncRNA that promoted NPC GEM resistance, cell proliferation, but inhibited cell apoptosis. Mechanistically, DYNLRB2-AS1 could directly bind to the DHX9 protein and prevent its interaction with the E3 ubiquitin ligase PRPF19, and thus blocking PRPF19-mediated DHX9 degradation, which ultimately facilitated the repair of DNA damage in the presence of GEM. Clinically, higher DYNLRB2-AS1 expression indicated an unfavourable overall survival of NPC patients who received induction chemotherapy. Overall, this study identified the oncogenic lncRNA DYNLRB2-AS1 as an independent prognostic biomarker for patients with locally advanced NPC and as a potential therapeutic target for overcoming GEM chemoresistance in NPC.

17.
J Blood Med ; 15: 265-273, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38895162

RESUMEN

Purpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China. Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and ß - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis. Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and ß globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes. Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.

18.
Am J Cancer Res ; 14(5): 2187-2201, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859851

RESUMEN

Salvage treatment for refractory metastatic colorectal cancer (mCRC) has yet to be identified. We aimed to evaluate the efficacy of a salvage lenvatinib-based regimen for refractory mCRC. In total, 371 patients were categorized into lenvatinib-based and non-lenvatinib-based groups. In the lenvatinib-based group, patients who received lenvatinib at a dosage of 10 mg/day were categorized into lenvatinib/chemotherapy and lenvatinib/immunotherapy subgroups. We reported overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. OS1 was used to measure the time from disease progression after TAS-102 and regorafenib treatment to death, while OS2 was used to measure the time from TAS-102 or regorafenib treatment to death. Propensity score matching analysis was employed to compare the characteristics between the lenvatinib-based and non-lenvatinib-based groups. Next-generation sequencing (NGS) information was analyzed using R software. The lenvatinib-based group exhibited longer OS than did the non-lenvatinib-based group (OS1, 11.4 vs. 3.7 months; OS2, 27.2 vs. 8.2 months). The disease control rate (DCR) and objective response rate (ORR) of the lenvatinib-based regimens were 69.4% and 6.1%, respectively. Lenvatinib/chemotherapy and lenvatinib/immunotherapy had similar PFS, OS, DCR, and ORR. The adverse effects were manageable. After propensity score matching, the lenvatinib-based group continued to exhibit significantly longer OS1 and OS2 than did the non-lenvatinib-based group. NGS analysis revealed that GNAS and KRAS alterations were associated with a worse treatment response and prolonged survival, respectively. In conclusion, a moderate-dose salvage lenvatinib-based regimen demonstrated promising clinical activity and tolerability in treating refractory mCRC.

19.
J Extracell Biol ; 3(1): e136, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38938675

RESUMEN

Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date. Here we explored stable reference genes through profiling the long RNA expression by RNA-seq following unsupervised analysis and validation studies. Candidate reference genes were identified using four algorithms: NormFinder, GeNorm, BestKeeper and the Delta Ct method, followed by validation. RNA profile showed uEVs contained abundant long RNAs information and the core transcriptome was related to cellular structures, especially ribosome which functions mainly as translation, protein and RNA binding molecules. Analysis of RNA-seq data identified RPL18A, RPL11, RPL27, RACK1, RPSA, RPL41, H1-2, RPL4, GAPDH, RPS27A as candidate reference genes. RT-qPCR validation revealed that RPL41, RPSA and RPL18A were reliable reference genes for long RNA quantification in uEVs from patients with diabetes mellitus (DM), diabetic nephropathy (DN), IgA nephropathy (IgAN) and prostate cancer (PCA). Interestingly, RPL41 also outperformed traditional reference genes in renal tissues of DN and IgAN, as well as in plasma EVs of several types of cancers. The stable reference genes identified in this study may facilitate development of uEVs as novel biomarkers and increase the accuracy and comparability of biomarker studies.

20.
Biosens Bioelectron ; 261: 116485, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38852323

RESUMEN

Developing quantitative biosensors of superoxide (O2•-) and nitric oxide (NO) anion is crucial for pathological research. As of today, the main challenge for electrochemical detection is to develop high-selectivity nano-mimetic materials to replace natural enzymes. In this study, the dendritic-like morphological structure of silver organic framework (Ag-MOF) was successfully synthesized via a solvothermal strategy. Owing to the introduction of polymeric composites results in improved electrical conductivity and catalytic activity, which promotes mass transfer and leads to faster electron efficiency. For monitoring the electrochemical signals of O2•- and NO, the Ag-MOF electrode substrate was produced by drop-coating, and composites were designed by cyclic voltammetric potential cycles. The designed electrode substrates demonstrate high sensitivity, wide linear concentrations of 1 nM-1000 µM and 1 nM-850 µM, and low detection limits of 0.27 nM and 0.34 nM (S/N = 3) against O2•- and NO. Aside from that, the sensor successfully monitored the cellular release of O2•-, and NO from HepG2 and RAW 264.7 living cells and has the potential to monitor exogenous NO release from donors of Diethylamine (DEA)-NONOate and sodium nitroprusside (SNP). Additionally, the developed system was applied to the analysis of O2•- and NO in real biological fluid samples, and the results were good satisfactory (94.10-99.57 ± 1.23%). The designed system provides a novel approach to obtaining a good electrochemical biosensor platform that is highly selective, stable, and flexible. Finally, the proposed method provides a quantitative way to follow the dynamic changes in O2•- and NO in biological systems.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Óxido Nítrico , Superóxidos , Técnicas Biosensibles/métodos , Óxido Nítrico/análisis , Óxido Nítrico/química , Humanos , Superóxidos/análisis , Superóxidos/química , Técnicas Electroquímicas/métodos , Ratones , Animales , Células Hep G2 , Células RAW 264.7 , Catálisis , Límite de Detección , Estructuras Metalorgánicas/química , Plata/química , Biomarcadores/análisis , Donantes de Óxido Nítrico/química
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