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1.
J Gynecol Oncol ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38606822

RESUMO

OBJECTIVE: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. METHODS: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. RESULTS: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). CONCLUSION: QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

2.
J Nat Med ; 78(3): 618-632, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38668832

RESUMO

Acute myeloid leukemia (AML) is a malignant disease that is difficult to completely cure. Polyphyllin I (PPI), a steroidal saponin isolated from Paris polyphylla, has exhibited multiple biological activities. Here, we discovered the superior cytotoxicity of PPI on AML cells MOLM-13 with an IC50 values of 0.44 ± 0.09 µM. Mechanically, PPI could cause ferroptosis via the accumulation of intracellular iron concentration and triggering lipid peroxidation. Interestingly, PPI could induced stronger ferroptosis in a short time of about 6 h compared to erastin. Furthermore, we demonstrate that PPI-induced rapid ferroptosis is due to the simultaneous targeting PI3K/SREBP-1/SCD1 axis and triggering lipid peroxidation, and PI3K inhibitor Alpelisib can enhance the activity of erastin-induced ferroptosis. Molecular docking simulations and kinase inhibition assays demonstrated that PPI is a PI3K inhibitor. In addition, PPI significantly inhibited tumor progression and prolonged mouse survival at 4 mg/kg with well tolerance. In summary, our study highlights the therapeutic potential of PPI for AML and shows its unique dual mechanism.


Assuntos
Diosgenina , Ferroptose , Leucemia Mieloide Aguda , Peroxidação de Lipídeos , Fosfatidilinositol 3-Quinases , Ferroptose/efeitos dos fármacos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Animais , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Diosgenina/farmacologia , Diosgenina/análogos & derivados , Diosgenina/uso terapêutico , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Saponinas/farmacologia , Saponinas/química
3.
IEEE Trans Vis Comput Graph ; 30(5): 2713-2723, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38457324

RESUMO

In this article, we propose a lightweight and flexible enhanced Tai Chi training system composed of multiple standalone virtual reality (VR) devices. The system aims to enable a hyper-realistic multi-user action training platform at low cost by displaying real-time action guidance trajectories, providing real-world impossible visual effects and functions, and rapidly enhancing movement precision and communication interest for learners. We objectively evaluate participants' action quality at different levels of immersion, including traditional coach guidance (TCG), VR, and mixed reality (MR), along with subjective measures like motion sickness, quality of interaction, social meaning, presence/immersion to comprehensively explore the system's feasibility. The results indicate VR performs the best in training accuracy, but MR provides superior social experience and relatively high accuracy. Unlike TCG, MR offers hyper-realistic hand movement trajectories and Tai Chi social references. Compared with VR, MR provides more realistic avatar companions and a safer environment. In summary, MR balances accuracy and social experience.


Assuntos
Realidade Aumentada , Tai Chi Chuan , Humanos , Gráficos por Computador , Movimento
4.
J Ovarian Res ; 17(1): 68, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539247

RESUMO

BACKGROUND: The gene cell division cycle associated 5 (CDCA5), also called sororin, has oncogenic characteristics and is upregulated in various carcinomas. Nevertheless, the involvement of CDCA5 in ovarian cancer (OC), a highly aggressive form of cancer, and the underlying mechanism of metastasis remain inadequately investigated. RESULTS: The bioinformatics data revealed a negative correlation between the patient's survival and CDCA5 expression, which was overexpressed in OC. Functional assays also confirmed high expression levels of CDCA5 in OC tissues and cells. This suggests that CDCA5 may potentially enhance the motility, migration, and proliferation of OC cells invitro. It impedes DNA damage and apoptosis in OC cells, inhibiting xenograft development in nude mice. The RNA sequencing results suggest CDCA5 is majorly associated with biological functions related to the extracellular matrix (ECM) and influences the transforming growth factor (TGF) signaling pathway. Moreover, subsequent functional investigations elucidated that CDCA5 facilitated the migration and invasion of OC cells viathe TGF-ß1/Smad2/3 signaling pathway activation. CONCLUSIONS: CDCA5 may be a strong potential therapeutic target for the treatment and management of OC.


Assuntos
Neoplasias Ovarianas , Fator de Crescimento Transformador beta1 , Animais , Camundongos , Humanos , Feminino , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Camundongos Nus , Linhagem Celular Tumoral , Neoplasias Ovarianas/patologia , Ciclo Celular , Proliferação de Células , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
5.
Ultrasonics ; 140: 107304, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38537516

RESUMO

Ultrasound-mediated transdermal drug delivery exhibits various advantages such as biocompatibility, controllability and safety, which attracts plenty of interests within biomedical field. Current researches mostly emphasizes the acoustic cavitation generated by planar or focused waves while neglecting other physics that occur during transportation. Our experimental study illustrates the presence of an acoustic vortex (AV) beam that exhibits a lower acoustic intensity and typically means a lower dose of inertial cavitation, yet achieves a more efficient delivery. Such a result calls for the fundamental mechanism of ultrasound-mediated transdermal transfer using the AV beam. In this work, according to our knowledge, the AV beam is firstly introduced to ultrasound-mediated transdermal medication delivery. The transversal acoustic radiation force (T-ARF), which is the primary characteristic carried by the acoustic vortex beam, and its contribution to the transport enhancement are investigated. It is shown that a focused AV (FAV) beam with a maximal acoustic pressure of 200 kPa induces a pN-level T-ARF, which promotes the enlargement of pores on the stratum corneum and thereby enhances the permeability, as compared with a zero-order (non-vortex) counterpart. This contribution of the T-ARF is validated by the experimental transport on the cellulose membrane, which exhibits a significantly increased membrane porosity and delivery efficiency. The favorable results introduce the new degree of freedom into the ultrasound-mediated transdermal drug transport based on AV beam, and thereby promotes the development of a combined control strategy for more precise and efficient transdermal drug delivery in conjunction with the administration of acoustic cavitation.


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Acústica , Animais , Absorção Cutânea , Pele/metabolismo , Pele/diagnóstico por imagem , Ondas Ultrassônicas , Permeabilidade , Suínos
6.
Phytother Res ; 38(4): 1815-1829, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38349045

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 µM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α-tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c-Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α-tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well-tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/ß-catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2-targeting drugs.


Assuntos
Chalconas , Sirtuína 2 , Neoplasias de Mama Triplo Negativas , Humanos , Sirtuína 2/farmacologia , Linhagem Celular Tumoral , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Tubulina (Proteína)/farmacologia , Tubulina (Proteína)/uso terapêutico , Proliferação de Células , Apoptose
7.
Food Chem ; 445: 138749, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38368699

RESUMO

In this study, a type of luminescent porous coordination network-224 (PCN-224) in alkaline conditions was synthesized with the dramatic fluorescence enhancement by 20.4 times, which was explained by the fact that the decrease of Zr4+ content in alkaline conditions resulted in the partial recovery of the electron cloud density of 4,4',4'',4'''-(Porphine-5,10,15,20-tetrayl) tetrakis(benzoic acid) (TCPP). Given the large overlap between the excitation spectrum of PCN-224 and the absorption band of Ag nanoparticles (Ag NPs), the coating of the Ag layer on PCN-224 triggered the fluorescence quenching effect, which was applied to "turn off" fluorescence immunoassay for sensitive detection of Escherichia coli O157:H7 (E. coli O157:H7) in milk. The proposed immunoassay reached a low limit of detection (LOD) of 3.3 × 102 CFU mL-1, 29.7 times more sensitive than the conventional ELISA. It will provide a novel alternative strategy for sensitively detecting pathogenic bacteria in the field of food safety.


Assuntos
Escherichia coli O157 , Nanopartículas Metálicas , Animais , Leite/microbiologia , Prata , Imunoensaio/métodos , Microbiologia de Alimentos
9.
Sci Total Environ ; 912: 168859, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38040355

RESUMO

Organophosphate flame retardants (OPFRs), a novel class of persistent pollutants, are widely distributed in the environment, and their potential health risks have garnered significant global attention in recent years. Crayfish is a popular freshwater crustacean product in China primarily sourced from the middle and lower reaches of the Yangtze River. The purpose of this study was to investigate the exposure levels of OPFRs in crayfish, assess the health and safety risks associated with crayfish consumption, and explore the bioaccumulation of OPFRs in environmental water and sediment on crayfish. Ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to analyze 7 common OPFRs in 106 crayfish samples and 76 environmental samples. The results revealed that OPFRs were detected at a high frequency of 100 % in crayfish, with tripropyl phosphate (TPP) being the predominant pollutant found in edible portions while also exhibiting secondary contamination within the crayfish food chain. Monte Carlo modeling combined with @risk risk assessment software demonstrated that TPP present in crayfish muscles had the most substantial impact on health effects, however, overall OPFR exposure did not pose significant risks to human health. Furthermore, analysis of OPFRs bioenrichment ability indicated that crayfish predominantly accumulated these compounds within their edible parts from surrounding environmental water sources, particularly highlighting TPP's potential for bioaccumulation.


Assuntos
Poluentes Ambientais , Retardadores de Chama , Animais , Humanos , Organofosfatos/análise , Retardadores de Chama/análise , Astacoidea , Bioacumulação , Cromatografia Líquida , Rios/química , Espectrometria de Massas em Tandem/métodos , Poluentes Ambientais/análise , Fosfatos/análise , Água/análise , Medição de Risco
10.
Front Oncol ; 13: 1210267, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38023216

RESUMO

Background: Immune checkpoint inhibitors (ICIs) have become the standard second-line treatment for advanced non-small cell lung cancer (NSCLC). Recent findings indicating an intertwined regulation of vascular endothelial growth factor (VEGF) signaling and immunosuppression in the tumor microenvironment suggest that the combination of ICIs and angiogenesis inhibitors could have synergistic antitumor activity, along with favorable tolerability. However, ICIs plus anti-angiogenesis therapy has not been widely evaluated. The purpose of this pilot study was to evaluate the efficacy and safety of ICIs plus recombinant human (rh)-endostatin as second-line treatment in advanced NSCLC with negative driver gene. Method: Prospectively evaluated the efficacy and safety of ICIs plus rh-endostain as second-line treatment in advanced NSCLC with negative driver gene. The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (ORR), and safety. Results: A total of 34 patients were recruited in this study. 18 patients received ICIs plus anti-angiogenesis therapy (ICIs combination therapy), and 16 patients received ICIs monotherapy. DCR was 88.9% vs 43.8% (P = 0.009). Median PFS (mPFS) was 8.3 months vs. 3.7 months (HR = 0.276, 95% CI 0.125-0.607, P = 0.001). Median OS (mOS) was 18.0 months vs 9.6 months (HR=0.364, 95% CI 0.147-0.902, P=0.009). In multivariate Cox regression analysis, ICI combination therapy prolonged PFS (HR = 0.069, 95% CI 0.019-0.185, P < 0.001) and OS (HR = 0.044, 95% CI 0.011-0.185, P < 0.001). We did not observe a significant difference in the incidence of adverse events (AEs) between the two groups (P > 0.05). Conclusions: Compared with ICIs monotherapy, ICIs combination therapy improves clinical response in patients with advanced NSCLC with negative driver gene, significantly prolongs PFS and OS, and does not significantly difference the incidence of AEs.

11.
Nanoscale ; 15(45): 18317-18327, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37921020

RESUMO

Quantum dots (QDs) are promising color conversion materials for efficient full-color micro light-emitting diode (micro-LED) displays owing to their high color purity and wide color gamut. However, achieving high-resolution QD patterns with enough thickness for efficient color conversion is challenging. Here, we demonstrate a facile and compatible approach by combining replicate molding, plasma etching and transfer printing to produce QD patterns with a sufficient thickness over ten micrometers in a wide range of resolutions. Our technique can remarkably simplify the preparation of QD inks and minimize optical damage to QD materials. The pixel resolution and thickness of QD patterns can be controlled by well-defining the microstructures of the molding template and the etching process. The transfer printing process allows QD patterns to be assembled sequentially onto a receiving substrate, which will further improve the original pixel resolution and avoid repetitive optical damage to QDs during the patterning process. Consequently, various QD patterns can be fabricated in this work, including perovskite quantum dot (PQD) patterns with a pixel resolution of up to 669 pixels per inch (ppi) and a maximum thickness of up to 19.74 µm, a wafer-scale high-resolution PQD pattern with sufficient thickness on a flexible substrate, and a dual-color pattern comprising green PQDs and red CdSe QDs. Furthermore, these fabricated QD films with a thickness of over 10 µm show improved color conversion when integrated onto a blue micro-LED, revealing the potential of our technique for full-color micro-LED displays.

12.
Lancet Oncol ; 24(10): 1134-1146, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37797632

RESUMO

BACKGROUND: Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. METHODS: This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450 mg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. FINDINGS: Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1-17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3-42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0-15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2-40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7-19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7-37·4). INTERPRETATION: Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. FUNDING: Akeso Biopharma. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Hepatocelular , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Hepáticas , Neoplasias do Colo do Útero , Humanos , Masculino , Feminino , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Antígeno CTLA-4 , Receptor de Morte Celular Programada 1 , Empatia , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
13.
Sci Rep ; 13(1): 16089, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37752203

RESUMO

Shot is one of the fundamental unit in the content structure of a film, which can provide insights into the film-director's ideas. By analyzing the properties and types of shots, we can gain a better understanding of a film's visual language. In this paper, we delve deeply into the task of shot type classification, proposing that utilizing multimodal video inputs can effectively improve the accuracy of the task, and that shot type classification is closely related to low-level spatiotemporal semantic features. To this end, we propose a Lightweight Weak Semantic Relevance Framework (LWSRNet) for classifying cinematographic shot types. Our framework comprises two modules: a Linear Modalities Fusion module (LMF Module) capable of fusing an arbitrary number of video modalities, and a Weak Semantic 3D-CNN based Feature Extraction Backbone (WSFE Module) for classifying shot movement and scale, respectively. Moreover, to support practical cinematographic analysis, we collect FullShots, a large film shot dataset containing 27K shots from 19 movies with professionally annotations for movement and scale information. Following experimental results validate the correctness of our proposed hypotheses, while our framework also outperforms previous methods in terms of accuracy with fewer parameters and computations, on both FullShots and MovieShots datasets. Our code is available at ( https://github.com/litchiar/ShotClassification ).

14.
J Helminthol ; 97: e55, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37427435

RESUMO

Nodular roundworms (Oesophagostomum spp.) are frequent parasites of the large intestine in several mammal species including humans and pigs, and their study often requires the use of infective larvae produced using several coproculture techniques. However, there is no published comparison of techniques to determine which yields the highest number of larvae. This study compares the number of larvae recovered from coprocultures made with charcoal, sawdust, vermiculite, and water in an experiment repeated twice using feces from a sow naturally infected with Oesophagostomum spp. at an organic farm. A higher number of larvae were recovered from coprocultures using sawdust relative to other types of media used, and this was consistent across the two trials. The use of sawdust to culture Oesophagostomum spp. larvae is rarely reported and our study suggests it can yield higher numbers relative to other media.


Assuntos
Nematoides , Esofagostomíase , Doenças dos Suínos , Humanos , Animais , Suínos , Feminino , Oesophagostomum/genética , Esofagostomíase/parasitologia , Larva , Contagem de Ovos de Parasitas , Fezes/parasitologia , Doenças dos Suínos/parasitologia , Mamíferos
15.
Asian J Surg ; 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37423860
16.
Transl Cancer Res ; 12(5): 1315-1324, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37304533

RESUMO

Background: Cervical cancer is one of the most common types of carcinoma in women and has high morbidity and mortality rates worldwide. Recurrent and metastatic disease remains difficult to treat. Receptor interacting protein kinase 1 (RIPK1) is a key molecule in mediating apoptosis, necroptosis, and inflammatory pathways downstream of death receptors and pattern recognition receptors. This study sought to explore the clinicopathological and prognosis significance of RIPK1 expression in cervical squamous cell carcinoma (CSCC). Methods: The data of 100 CSCC patients who underwent curative surgery from 2019 to 2020 were retrospectively included in this study. We collected the clinicopathological information of the patients and detected RIPK1 protein expression using immunohistochemistry. The Chi-square test and a 1-way analysis of variance were used to make comparisons between groups stratified by RIPK1 expression. A Pearson linear correlation analysis was used to evaluate the association between RIPK1 expression and the clinicopathological characteristics of the patients. A Cox regression analysis and Kaplan-Meier curves were used to analyze overall survival (OS) and progression-free survival (PFS). A multivariable regression analysis was conducted to identify the risk factors for an impaired prognosis in CSCC. Results: RIPK1 was found to be overexpressed in the CSCC tissues. RIPK1 expression was significantly associated with age, the preoperative serum squamous cell carcinoma antigen (SCC-Ag) level, lymph node metastasis, invasion depth, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor size, PFS, and OS (P<0.05). The PFS and OS differed significantly among patients with RIPK1 expression (P<0.05). The multivariate analysis showed that RIPK1 was not independent risk factors for PFS and OS in CSCC patients (P>0.05). Conclusions: The expression of RIPK1 was significantly upregulated in CSCC and was associated with the clinicopathological features of CSCC. RIPK1 might serve as a novel marker that can be used to predict the prognosis of CSCC patients and as a biological target for the treatment of CSCC.

17.
Int J Mol Sci ; 24(6)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36982538

RESUMO

Salvia miltiorrhiza Bunge (Danshen) has been widely used to treat cancer and cardiovascular diseases in Chinese traditional medicine. Here, we found that Neoprzewaquinone A (NEO), an active component of S. miltiorrhiza, selectively inhibits PIM1. We showed that NEO potently inhibits PIM1 kinase at nanomolar concentrations and significantly suppresses the growth, migration, and Epithelial-Mesenchymal Transition (EMT) in the triple-negative breast cancer cell line, MDA-MB-231 in vitro. Molecular docking simulations revealed that NEO enters the PIM1 pocket, thereby triggering multiple interaction effects. Western blot analysis revealed that both NEO and SGI-1776 (a specific PIM1 inhibitor), inhibited ROCK2/STAT3 signaling in MDA-MB-231 cells, indicating that PIM1 kinase modulates cell migration and EMT via ROCK2 signaling. Recent studies indicated that ROCK2 plays a key role in smooth muscle contraction, and that ROCK2 inhibitors effectively control the symptoms of high intraocular pressure (IOP) in glaucoma patients. Here, we showed that NEO and SGI-1776 significantly reduce IOP in normal rabbits and relax pre-restrained thoracic aortic rings in rats. Taken together, our findings indicated that NEO inhibits TNBC cell migration and relaxes smooth muscles mainly by targeting PIM1 and inhibiting ROCK2/STAT3 signaling, and that PIM1 may be an effective target for IOP and other circulatory diseases.


Assuntos
Doenças Cardiovasculares , Neoplasias de Mama Triplo Negativas , Humanos , Ratos , Animais , Coelhos , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Relaxamento Muscular , Transição Epitelial-Mesenquimal , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Movimento Celular , Proliferação de Células , Proteínas Proto-Oncogênicas c-pim-1/metabolismo , Fator de Transcrição STAT3/metabolismo , Quinases Associadas a rho/metabolismo
18.
Analyst ; 148(7): 1437-1441, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36919562

RESUMO

Formaldehyde (FA) and viscosity play multiple roles in human health and diseases, and viscosity has great regional differences due to the diversity of subcellular organelles. However, it is challenging to achieve dual detection of viscosity and FA in subcellular organelles. Herein, we developed a near infrared (NIR) fluorescent probe FA-Cy, which can simultaneously monitor the viscosity and FA concentration of mitochondria in living cells. The probe could detect mitochondrial viscosity and exogenous and endogenous FA in living cells and zebrafish.


Assuntos
Corantes Fluorescentes , Peixe-Zebra , Animais , Humanos , Corantes Fluorescentes/toxicidade , Células HeLa , Viscosidade , Imagem Óptica/métodos , Mitocôndrias , Formaldeído
19.
Vet Parasitol ; 314: 109856, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36565642

RESUMO

Swine parasites are a challenge for organic and alternative pig farmers and represent suboptimal animal health because use of chemical prophylaxis is not recommended. There is no comprehensive study of how prevalent gastrointestinal parasites are in organic or alternative pig farms across the USA. This study investigates prevalence, abundance, and intensity measures for three intestinal roundworm parasites (Ascaris suum, Oesophagostomum spp. and Trichuris suis) on organic and alternative swine farms by quantifying their eggs in pig feces, pastured soil, and bedding. Nine farms raising pigs in bedded facilities across four states (Iowa, Minnesota, Pennsylvania, and Wisconsin) were sampled, and analysis of parasite egg counts from feces indicate that 88.9%, 55.5%, and 44.4% of farms were infected with A. suum, Oesophagostomum spp. and T. suis, respectively. Prevalence, mean abundance, and mean intensity of eggs per gram (EPG) in feces for A. suum and T. suis were higher in growing and finishing pigs, whereas they were higher for Oesophagostomum spp. in finishing pigs and sows. Prevalence and abundance with A. suum eggs in feces were higher in organic certified farms, whereas abundance of Oesophagostomum spp. and T. suis was lower than those in alternative farms. Fewer eggs were recovered from soils than bedding samples, but their presence in both substrates confirmed that dispersal stages occur in farms. Overall, our results indicate that intestinal parasite infection across organic and alternative swine farms in the USA is common, and not surprising given that few options to control infection within organic regulations are available.


Assuntos
Enteropatias Parasitárias , Nematoides , Parasitos , Doenças dos Suínos , Animais , Suínos , Feminino , Fazendas , Óvulo , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/veterinária , Enteropatias Parasitárias/parasitologia , Oesophagostomum , Doenças dos Suínos/parasitologia , Fezes/parasitologia , Contagem de Ovos de Parasitas/veterinária
20.
Research (Wash D C) ; 6: 0280, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38434241

RESUMO

With unlimited topological modes in mathematics, the fractional orbital angular momentum (FOAM) demonstrates the potential to infinitely increase the channel capacity in acoustic-vortex (AV) communications. However, the accuracy and stability of FOAM recognition are still limited by the nonorthogonality and poor anti-interference of fractional AV beams. The popular machine learning, widely used in optics based on large datasets of images, does not work in acoustics because of the huge engineering of the 2-dimensional point-by-point measurement. Here, we report a strategy of phase-dislocation-mediated high-dimensional fractional AV communication based on pair-FOAM multiplexing, circular sparse sampling, and machine learning. The unique phase dislocation corresponding to the topological charge provides important physical guidance to recognize FOAMs and reduce sampling points from theory to practice. A straightforward convolutional neural network considering turbulence and misalignment is further constructed to achieve the stable and accurate communication without involving experimental data. We experimentally present that the 32-point dual-ring sampling can realize the 10-bit information transmission in a limited topological charge scope from ±0.6 to ±2.4 with the FOAM resolution of 0.2, which greatly reduce the divergence in AV communications. The infinitely expanded channel capacity is further verified by the improved FOAM resolution of 0.025. Compared with other milestone works, our strategy reaches 3-fold OAM utilization, 4-fold information level, and 5-fold OAM resolution. Because of the extra advantages of high dimension, high speed, and low divergence, this technology may shed light on the next-generation AV communication.

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